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1
Kosse, C. L. "Functional properties of GAD65 neurons in the lateral hypothalamus". Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10044863/.
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The brain’s ability to sense energy levels and adjust behaviour accordingly is vital for survival in mammals. The lateral hypothalamus (LH), which contains energy-spending (orexin) and energy-conserving melanin-concentrating hormone (MCH) neurons, is thought to be the brain’s master energy sensor and generator of motivated behaviour. Recently, other classes of non-MCH, non-orexin neurons, such as vesicular GABA transporter (VGAT) and glutamic acid decarboxylase 65 (GAD65) expressing neurons, have been discovered in the LH. VGATLH neurons have been shown to be essential for appetitive and consummatory behaviour. However, the properties and behavioural roles of GAD65LH neurons remain unclear, and are the focus of this thesis. The thesis’ three parts examine cellular, circuit, and behavioural roles of GAD65LH neurons. Firstly, whole cell patch clamping was used to determine firing responses of GAD65LH neurons to injections of oscillatory input currents. GAD65LH neurons were found to have similar frequency-preferences of firing resonance to those of VGAT and MCH neurons, whilst orexin neurons showed a different, “high frequency inhibited” frequency-preference profile. Moreover, histochemistry was employed to characterise GAD65LH neurons further by quantifying their overlap with other GABAergic LH cell types. It was found that GAD65LH neurons overlapped only partially with VGATLH neurons, and that neuropeptide Y (NPY) and leptin receptor (LepRb) expressing neurons were largely distinct from GAD65LH cells. Secondly, cell-type specific channelrhodopsin-assisted circuit mapping was used to probe up- and downstream functional targets of GAD65LH neurons. It was found that GAD65LH neurons were excited by orexin neurons and inhibited by VGATLH neurons, and that they preferentially inhibited MCHLH and NPYLH neurons. Finally, chemogenetic excitation or inhibition of GAD65LH cell activity was used to investigate the role of these cells in behaviour. It was found that GAD65LH neurons were weight-loss-promoting, and essential and sufficient for normal locomotor activity. Overall, these results define and characterise a new cellular network component in LH function.
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Carus-Cadavieco, Marta. "Coordination of innate behaviors by GABAergic cells in lateral hypothalamus". Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19135.
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Der laterale Hypothalamus (LH) reguliert angeborene Verhaltensweisen. Ob und wie die Koordination von hypothalamischen Neuronengruppen Verhaltensübergänge reguliert, blieb jedoch unbekannt. In dieser Arbeit wurde Optogenetik mit neuronalen Ableitungen in verhaltenden Mäusen kombiniert. LHVgat Neurone erhöhten ihre Aktivitätsrate während Übergängen vom NREM-Schlaf zum Wachzustand. LHVgat Zellen projizieren zum Nucleus reticularis des Thalamus (RTN). Optogenetische Aktivierung von Vgat Ausgängen im RTN führte eine starke, frequenzabhängige Inhibierung von RTN Zellen herbei und replizierte Verhaltenszustands-abhängige Aktivitätsraten in RTN Neuronen. Ableitungen von LH Neuronen während Umgebungserkundung ergaben, dass 65% der LH Neurone ihre Aktivitätsrate erhöhten, wenn das Tier began sich fortzubewegen. 'Top-down’ Vorderhirn Innervation des LH erfolgt größtenteils durch Signale ausgehend vom lateralen Septums (LS). Während spontaner Umgebungserkundung und freiem Zugang zu Futter wiesen der LH und das LS Gamma-Oszillationen (30-90 Hz) auf, welche neuronale Aktivität innerhalb und zwischen diesen beiden Gehirnregionen synchronisierten. Optogenetische Stimulation von Somatostatin-positiven GABAergen Projektionen zum LH mit Gamma-Frequenz förderte die Nahrungssuche und erhöhte die Wahrscheinlichkeit des Betretens der Nahrungszone. Inhibitorische Signale des LS bewirkten eine Unterteilung der LH Neurone: entsprechend ihrer Aktivität im Bezug zur Nahrungsstelle wurden sie während bestimmter Phasen der Gamma-Oszillation aktiviert. Dabei führte optogenetische Stimulation von LS-LH Neuronen mit Gamma-Frequenz keine Veränderung bei der Nahrungsaufnahme selbst herbei. Insgesamt liefert diese Arbeit neue Einsichten über die Funktion der neuronalen Netzwerke des LH, welche durch Signalgebung mit unterschiedlichen Zeitskalen über die Koordination mit vor- und nachgeschalteten neuronalen Netzwerken Übergange zwischen verschiedenen angeborenen Verhaltensweisen regeln.Lateral hypothalamus (LH) is crucial for regulation of innate behaviors. However, it remained unknown whether and how temporal coordination of hypothalamic neuronal populations regulates behavioral transitions. This work combined optogenetics with neuronal recordings in behaving mice. LHVgat cells were optogenetically identified. LHVgat neurons increased firing rates upon transitions from non-REM (NREM) sleep to wakefulness, and their optogenetic stimulation during NREM sleep induced a fast transition to wakefulness. LHVgat cells project to the reticular thalamic nucleus (RTN). Optogenetic activation of LHVgat terminals in the RTN exerted a strong frequency-dependent inhibition of RTN cells and replicated state-dependent changes in RTN neurons activity. Recordings of LH neurons during exploration revealed that 65% of LH neurons increased their activity upon the onset of locomotion. Top-down forebrain innervation of LH is provided, to a great extent, by inhibitory inputs from the lateral septum (LS). During spontaneous exploration in a free-feeding model, LS and LH displayed prominent gamma oscillations (30-90 Hz) which entrained neuronal activity within and across the two regions. Optogenetic gamma-frequency stimulation of somatostatin-positive GABAergic projections to LH facilitated food-seeking, and increased the probability of entering the food zone. LS inhibitory input enabled separate signaling by LH neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. In contrast to increased food intake during optogenetic stimulation of LHVgat cells, food intake during gamma-rhythmic LS-LH stimulation was not changed. Overall this works provides new insight into the function of LH circuitry, that employs signalling at different time scales, which, in coordination with upstream and downstream circuits, regulates transitions between innate behaviors.
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Boucher-Thrasher, Annette. "Evidence for anatomical connectivity between lateral hypothalamic and lateral preoptic area brain stimulation sites". Thesis, University of Ottawa (Canada), 1987. http://hdl.handle.net/10393/5246.
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Scollon, Jennifer Margaret. "The function of the lateral hypothalamus with regard to gustatory and reward related processes". Thesis, University of St Andrews, 1999. http://hdl.handle.net/10023/14701.
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The lateral hypothalamus (LH) has been shown to be involved in consummatory behaviour by a number of different experimental techniques including behavioural and electrophysiological methods. Lesion studies indicate that loss of the LH does not significantly alter normal feeding and drinking in the home cage, responding to food and water deprivation or responding to glucose or salt adulteration of the diet. However, when injected with dehydrating, dipsogenic or glucoprivic agents, the so called needle challenges, LH lesioned rats failed to respond as sham lesioned rats. This is despite the fact that the injections described induced the same deficits in homeostasis as food and water deprivation. Both sets of challenges are cued by internal visceral signals but only deprivation has additional environmental cues; animals are aware that their food or water are missing and may even anticipate its return. These different types of cues may be conveyed by different neural pathways and it has been proposed that lesioning the LH removes a pathway whereby visceral signals reach higher neural structures thus accounting for why LH lesioned rats responded appropriately to deprivation but not needle challenges. The present study examined the hypothesis that the LH acts as a gateway for signals concerning internal state to reach structures involved in behavioural planning and action. This was tested by the use of tests known to be susceptible to damage or change in the paraventricular system, responsible for monitoring the internal milieu, and frontostriatal systems responsible for behavioural planning and execution. The functions known to be dependent on the paraventricular system which were tested were conditioned taste aversion, benzodiazepine induced hyperphagia and taste perception but no deficits were found in responding in any of these procedures as a result of lesioning the LH. The functions known to be dependent on frontostriatal systems that were examined with LH lesioned rats were conditioned reinforcement and conditioned place preference but again few deficits were found. Hence, the present study failed to provide evidence to substantiate the hypothesis that the LH stands as an interface between the paraventricular system and frontostriatal systems. However, it did provide evidence that lesioning the LH induces deficits in consummatory responses dependent on the circumstances of the tests.
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Oh, Jeremy Jaehwan. "Posterior lateral hypothalamus stimulation confirms brain reward site stimulation-induced hyperalgesia". Thesis, Boston University, 2012. https://hdl.handle.net/2144/12548.
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Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.Pain is known as one of the most important physical sensations that contribute to animal survival. Kornetsky and colleagues (201 0) established mesencephalic reticular formation (MRF) and midbrain forebrain bundle (MFB) thresholds separately and found that simultaneous stimulation of the sites significantly lowered MRF escape thresholds. They also found that the simultaneous stimulation of the sites eliminated the analgesic effect--that is, raising the MRF threshold--of morphine. In an effort to better understand the interaction between rewarding brain stimulation and nociceptive pain, this study expands upon the previous experiment by implanting an electrode in the ventral tegmental area (VTA). However, during the post-mortem histological review, it was found that the rewarding electrodes were implanted in the posterior lateral hypothalamus (PLH), not in the VTA. Our overall results of this experiment demonstrate similar findings as the previous study (Kornetsky et al., 2010). The simultaneous stimulation of the MRF and PLH significantly lowered MRF escape thresholds and eliminated the analgesic effects of morphine. A very low, subthreshold intensity of stimulation to the PLH yielded significantly increased sensitivity to MRF stimulation. Furthermore, the results show that morphine did not lower BSE threshold, when the MRF was simultaneously stimulated with the PLH. An examination of the rewarding electrode placements found in the simultaneous MRF and MFB stimulation experiment by Kornetsky and colleagues (2010) also show rewarding electrode in the PLH, which corroborates with the results in this experiment.
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Morutto, Sara Lidia. "Role of the perifornical region of the lateral hypothalamus in appetitive conditioning". Thesis, University of York, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288040.
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Venner, Anne. "The electrical activity of lateral hypothalamic neurons and its regulation by nutrients and ethanol". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610286.
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Nieh, Edward H. (Edward Horng-An). "Lateral hypothalamic control of motivated behaviors through the midbrain dopamine system". Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/106440.
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Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2016.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 209-231).
The lateral hypothalamus and ventral tegmental area are two brain regions that have long been known to be involved in processing reward and the control of feeding behaviors. We continue work in this area by identifying the functional connectivity between these two regions, providing evidence that LH neurons projecting to the VTA encode conditioned responses, while LH neurons innervated by the VTA encode conditioned and unconditioned stimuli. Activation of the LH-VTA projection can increase compulsive sugar seeking, while inhibition of the projection can suppress this behavior without altering normal feeding due to hunger. We can separate this projection into the GABAergic and glutamatergic components, and we show that the GABAergic component plays a role in promoting feeding and social interaction by increasing motivation for consummatory behaviors, while the glutamatergic component largely plays a role in the suppression of these behaviors. Finally, we show that activation of the GABAergic component causes dopamine release downstream in the nucleus accumbens via disinhibition of VTA dopamine neurons through VTA GABA neurons. Together, these experiments have profoundly elucidated the functional roles of the individual circuit components of the greater mesolimbic dopamine system and provided potential targets for therapeutic intervention of overeating disorders and obesity..
by Edward H. Nieh.
Ph. D. in Neuroscience
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Martianova, Ekaterina. "The role of the lateral hypothalamic neural outputs in motivated behaviour". Doctoral thesis, Université Laval, 2020. http://hdl.handle.net/20.500.11794/67902.
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Comprendre comment le cerveau traite l’information est l’une des questions les plus intrigantes auxquelles les neurosciences modernes sont confrontées. L’étude actuelle vise à caractériser comment l’hypothalamus latéral (HL) traite l’information vers des cibles cérébrales en aval afin de guider des réponses comportementales appropriées. L’HL est une zone du cerveau qui régule des comportements vitaux tels que les fonctions autonomes et endocriniennes, l’équilibre homéostatique, la régulation du métabolisme et les cycles veille-sommeil. De plus, des études récentes soulignent son importance dans le traitement de l’aversion et de la récompense. L’HL envoie des projections neurales à de nombreux noyaux cérébraux connus pour traiter des signaux qui jouent un rôle important pour guider et orchestrer des réponses comportementales appropriées. Des expériences visant a déterminer les connections afferentes et efférentesde l’HL ont démontré que trois noyaux cérébraux importants reçoivent des projections importantes de l’HL. Il s’agit de l’habenula latéral (HbL), de l’aire tegmentale ventrale (ATV) et du noyau raphe dorsal (NRD). L’HbL est le principal centre de déception du cerveau : son activité augmente spécifiquement lorsqu’un animal est soumis à des stimuli aversifs ou en l’absence de récompenses attendues, jouant un rôle important dans la signalisation d’une erreur de prédiction de punition. L’ATV dopaminergique est le principal centre de récompense du cerveau. Il joue un rôle important dans l’encodage de la valeur des récompenses, l’apprentissage du renforcement et la motivation. Le NRD est le principal centre de sérotonine jouant un rôle important dans le traitement des émotions et les réponses adaptatives. Pour examiner spécifiquement la contribution des sorties neuronales de l’HL chez les souris en mouvement libre, nous avons utilisé une technique d’imagerie avancée du calcium – système de photométrie à fibres. La photométrie à fibres est une approche puissante qui combine des indicateurs de calcium codés génétiquement et des fibres optiques multimodes pour monitorer l’activité neuronale chez les animaux en mouvement libre, ce qui est essentiel pour comprendre comment des groupes spécifiques de neurones sont impliqués dans le contrôle ou la réponse à une action ou à un stimulus. Dans le premier chapitre, je présente un protocole qui a été développé pour une détection fiable des signaux de calcium à l’aide d’un système de photométrie multifibre. Le protocole détaille les composantes d’un système de photométrie multifibres, la méthode pour accéder aux structures profondes du cerveau pour délivrer et collecter la lumière, et une méthode pour prendre en compte les artefacts de mouvement avant et pendant les enregistrements. En outre,je présente un algorithme de traitement des signaux enregistrés qui tient compte des sources communes d’artefacts qui sont inévitables pendant les enregistrements. Dans le deuxième chapitre, je présente les résultats de l’étude du rôle fonctionnel de trois sorties neurales de l’HL vers le NRD, l’ATV et l’HbL. En utilisant le protocole décrit dans le premier chapitre, l’activité dans les voies HL→NRD, HL→ ATV et HL→HbL a été simultanément enregistrée lors de réponses comportamentales dans des contextes d’aversion et de récompense. Nous avons constaté que l’activité à ces trois sorties neurales de l’HL augmentait avec des stimuli et des signaux prédictifs de stimuli aversifs. L’activité neuronale augmente également lors des réponses comportementales motivées spontanées et diminue lors de l’immobilité comportementale. L’activation optogénétique indépendante des terminaisons axonales de l’HL au niveau de l’HbL, l’ATV ou le NRD était suffisante pour augmenter la mobilité, mais a eu des effets différents dans d’autres tests comportementaux. Dans l’ensemble, nous proposons que l’HL envoie des signaux complémentaires aux cibles en aval pour traiter les informations engagées pour promouvoir des comportements motivés. En annexe, je présente un ensemble d’analyse de données python qui a été développé pour traiter tous les enregistrements de photométrie à fibre optique présentés dans l’étude actuelle. Cet ensemble permet de combiner, de stocker et d’analyser les enregistrements de plusieurs souris, essais et différentes expériences avec diverses mesures, événements comportementaux et stimuli de manière standardisée.Understanding how brain processes information is the one of the most intriguing questions that modern neuroscience faces. The current study aims to characterize how the lateral hypothalamus (LH) processes information to downstream brain targets to guide proper behavioral responses. The LH is a brain area that regulates vital behaviors such as autonomic and endocrine functions, homeostatic balance, regulation of metabolism, and sleep-wake cycles. Moreover, recent studies point out its importance in aversive and appetitive processing. The LH sends neural projections to many brain nuclei known to process signals that play important roles to guide and orchestrate proper behavior responses. Tracing experiments demonstrated that three important brain nuclei receive significant inputs from the LH, the lateral habenula (LHb), the ventral tegmental area (VTA), and the dorsal raphe nucleus (DRN). The LHb is the main disappointment center of the brain: its activity specifically increases when an animalis presented an aversive stimuli or in the absence of expected rewards, playing an important role in signaling punishment prediction error. The dopaminergic VTA is the main brain reward center. It plays important roles in reward-value encoding, reinforcement learning and motivation. The DRN is the main serotonin center playing and important role in emotion processing and adaptive responses. To specifically examine the contribution of LH neural outputs in freely moving mice, we used an advanced calcium imaging technique – fiber photometry system. Fiber photometry is a powerful approach that combines genetically encoded calcium indicators and multimode optical fibers to monitor neuronal activity in freely moving animals, which is critical to understand how specific groups of neurons play in directing or responding to an action or a stimulus. In the first chapter, I present a protocol that was developed for reliable detection of calcium signal using a camera-based multi-fiber photometry system. The protocol details the components of a multi-fiber photometry system, a method to access deep brain structures to deliverand collect light, and a method to account for motion artifacts before and during recordings. Additionally, I present an algorithm for processing of recorded signals that accounts common sources of artefacts that are inevitable during recordings. In the second chapter, I present results of the investigation of the functional role of three LH outputs to the DRN, VTA, and LHb. Using the protocol described in the first chapter, activity in the LH→DRN, LH→ VTA and LH→LHb pathways were simultaneously recorded during motivated responses in aversive and appetitive contexts. We found that these three LH neural outputs increased activity with aversive stimuli and cues predicting them. The neural activity also increased at onsets of spontaneous motivated behavior responses and decreased duringbehavioral immobility. Independent optogenetic activation of axon terminals in LHb, VTA,or DRN was sufficient to increase mobility, but had different effects in other behavioural tests. Altogether, we propose that LH sends complementary signals to the downstream targets to process information engaged in motivated behaviors. In the annex, I present a data analysis python package that was developed to process all fiber photometry recordings presented in the current study. The package allow to combine, store, and analyze recordings from multiple mice, trials, and different experiments with various measurements, behavioural events, and stimuli in a standardized way.
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Clark, Judith. "Examinations of the nature of the deficits induced by n-methyl-D-aspartic acid lesions of the rat lateral hypothalamus". Thesis, University of St Andrews, 1990. http://hdl.handle.net/10023/14703.
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The lateral hypothalamic syndrome of aphagia, adipsia akinesia and sensorimotor impairments induced by electrolytic lesions of the lateral hypothalamus (LH) has been suggested to be due to the destruction of two components of a single system controlling feeding and drinking behaviour. While the "motor" component has been attributed to disruption of dopaminergic fibres, it has been suggested that destruction of intrinsic LH neurones induces a "motivational" deficit. The nature of this motivational deficit was investigated using the excitotoxin N-methyl-d~aspartic acid (NMDA) to lesion cell bodies and leave fibres of passage intact. Such lesions induced temporary reductions in body weight, food and water intake and residual deficits in response to some physiological challenges. Most animals recovered food and water intake and body weight gain after a short period of time. It was shown that LH lesioned rats were able to perceive and respond to the palatability of food/fluid; they responded physiologically to intracellular dehydration caused by hypertonic saline injections, although they did not respond behaviourally; they responded as controls to a battery of long-term, "positive" physiological challenges, but not to short-term, "negative" ones; and they displayed increased rate of development of schedule-induced polydipsia and tail pinch-induced eating, demonstrating that they had no motor impairments and that they did not have an "activational" deficit. These results indicate that the LH cannot be regarded as a feeding or drinking "centre" and that the motivational deficit following lesions of the LH is of a very complex nature. The implications of these data for the function of the LH are discussed in relation to electrophysiological and anatomical studies.
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Yosypenko, V. R. "Submicroscopic changes of the lateral preoptic nucleus of the hypothalamus under light stimulation". Thesis, БДМУ, 2022. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/19379.
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Whitehurst, Laurie. "Recovery of rewarding effectiveness of lateral hypothalamic self-stimulation following radiofrequency lesions". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ57079.pdf.
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Bauco, Pasqualino. "Characterization of the synergistic effects of cocaine with lateral hypothalamic brain stimulation reward". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0006/NQ39620.pdf.
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Karnani, Mahesh Miikael. "Macronutrient sensing by hypocretin/orexin and GAD65 neurons of the lateral hypothalamic area". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610247.
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Reppucci, Christina Jean. "The functional forebrain circuitry of fear-cue inhibited feeding in food-deprived rats: Evidence from complementary pathway tracing and Fos induction maps studies". Thesis, Boston College, 2015. http://hdl.handle.net/2345/bc-ir:104569.
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Thesis advisor: Gorica D. PetrovichThe drive to eat, like most motivated behaviors, is controlled by both intrinsic signals from the body as well as extrinsic signals from the environment. Although these factors often act in concert, in some instances environmental cues can override the body’s homeostatic signals. Prior work investigating the ability of learned cues to promote overeating in the absence of hunger identified a critical forebrain network composed of the amygdala, medial prefrontal cortex (mPFC), and lateral hypothalamus (LHA). We hypothesized that a similar forebrain network may also be critical when learned fear-cues inhibit eating despite hunger. The amygdala, mPFC and LHA are each anatomically and functionally positioned to influence feeding, and evidence suggests they could work together to support the fear-cue’s ability to inhibit feeding by overriding homeostatic hunger signals triggered by food-deprivation. Prior anatomical work identified direct pathways between these three large, heterogeneous regions; however, less is known about the organization of the underlying circuitries, especially between distinct nuclei and/or subdivisions that comprise these structures. Study 1 used a dual retrograde tract tracing design to map the topographical organization of the connections between the amygdala, mPFC, and LHA in detail, and to determine whether amygdalar pathways to the mPFC and to LHA originated from the same or different neurons. We found evidence for multiple, topographically organized, direct pathways from the amygdala to the LHA, and separate pathways from the amygdala to areas of the mPFC that send direct projections to the LHA. Importantly, nearly all amygdalar projections to the mPFC and to the LHA originated from different neurons, suggesting that amygdala and amygdala-mPFC processing influence the LHA independently. Study 2 used immediate early gene induction to map the patterns of functional activation within this amygdala-prefrontal-lateral hypothalamic network during the expression of fear-cue inhibited feeding behavior, and to assess whether these patterns were similar in males and females. We found differential activation across the network, and activation patterns related to the presentation of fear-cues, the presence of food-related cues, and the amount of food consumed were associated within distinct cell groups in the amygdala, mPFC, and LHA. Together, the studies presented in this dissertation provide anatomical and functional maps for future interrogation of the circuitry underlying fear-cue inhibited feeding
Thesis (PhD) — Boston College, 2015
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Psychology
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BAYER, LAURENCE. "Phenotype chimique, organisation et fonctions des neurones a mch (hormone de melano-concentration) chez le rat : etudes in vivo et en cultures de tranches hypothalamiques (doctorat : sciences de la vie et de la sante)". Besançon, 2000. http://www.theses.fr/2000BESA3705.
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Furigo, Isadora Clivatti. "Papel do hipotálamo ventromedial e da parte tuberal do hipotálamo lateral no comportamento de agressão maternal". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-09112012-095512/.
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O comportamento agressivo maternal é desenvolvido por ratas lactantes com o intuito de preservar a vida de sua prole. Nesse estudo demonstramos que a Área Hipotalâmica de Ataque (HAA), particularmente a porção ventrolateral do núcleo ventromedial (VMHvl) e a parte tuberal do hipotálamo lateral (LHAtu), apresentam um papel crítico para a expressão do comportamento, ao correlacionarmos os níveis de agressão maternal com a ativação de tais setores, e detectarmos prejuízo no comportamento em um grupo submetido a lesões citotóxicas bilaterais por NMDA circunscritas a 1/3 caudal da HAA, e em outro grupo lesões que se estenderam por 2/3 caudais do eixo rostro caudal da HAA. Os parâmetros não agressivos não apresentaram diferenças entre os grupos, assim como os comportamentos maternais, indicando que as lesões não afetaram o cuidado das fêmeas com a sua prole. Em uma análise da densidade de células Fos positivas de possíveis alvos dessas estruturas hipotalâmicas estudadas, não detectamos diferenças estatísticas entre os grupos com lesão e o grupo controle.The maternal aggression is developed by lactant dams to preserve their offsprings. In the present study we show that Hypothalamic Attack Area (HAA), particularly the ventrolateral part of ventromedial nucleus (VMHvl) and the tuberalis part of the lateral hypothalamus (LHAtu), have a critical role in the expression of this behavior. We have correlated the maternal aggression levels with the activation of this parts and we have detected behavioral damage at both groups with bilateral NMDA lesions at 1/3 caudal of HAA or 2/3 caudal of HAA, compared with control group. The non-agressive parameters did not show diferences among groups, as well as the maternal behavior, indicating that the lesions did not affect the maternal care. We have further analyzed the pattern of Fos expression in the brainstem targets of these hypothalamic regions in the NMDA lesioned dams, but couldnt find any difference between lesioned and intact groups.
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Hervé, Christine. "Etude de l'expression des genes codant l'hormone de melanoconcentration et la dynorphine par des neurones de l'hypothalamus lateral du rat dans diverses circonstances experimentales". Besançon, 1997. http://www.theses.fr/1997BESA3711.
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Oda, Keiji. "Effects of dopamine depletion in the nucleus accumbens on lateral hypothalamic self-stimulation in the rat". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ54279.pdf.
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Yosypenko, V. R. "Correction of immunohistochemical disorders of the lateral preoptic nucleus of the hypothalamus of mature rates caused by constant lighting". Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18511.
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Fulton, Stephanie E. "The lateral hypothalamus and energy balance, facilitation and inhibition of perifornical self-stimulation by long- and short-term metabolic signals". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ39058.pdf.
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Carus-Cadavieco, Marta [Verfasser], Tatiana [Gutachter] Korotkova, Peter [Gutachter] Hegemann y Rüdiger [Gutachter] Krahe. "Coordination of innate behaviors by GABAergic cells in lateral hypothalamus / Marta Carus-Cadavieco ; Gutachter: Tatiana Korotkova, Peter Hegemann, Rüdiger Krahe". Berlin : Humboldt-Universität zu Berlin, 2018. http://d-nb.info/1185497714/34.
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BAHJAOUI, BOUHADDI MALIKA. "Etudes morphofonctionnelles de deux populations originales de neurones peptidergiques de l'hypothalamus lateral, l'une secretant le precurseur de la mch, l'autre un peptide immunologiquement apparente a la prolactine". Besançon, 1993. http://www.theses.fr/1993BESA3705.
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Grillon, Sophie. "Etude de deux populations de neurones peptidergiques de l'hypothalamus lateral de rongeurs : les neurones a piap (peptide immunologiquement apparente a la prolactine) et les neurones a mch (hormone de melanoconcentration)". Besançon, 1997. http://www.theses.fr/1997BESA3715.
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Mitra, Arojit. "The role of lateral septum and anterior hypothalamic area in mediating the interactive effects of stress and palatable food". Doctoral thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27775.
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Le mode de vie stressant et sédentaire associé à un environnement moderne obésogène sont les principales causes des troubles alimentaires et de l’obésité induite par le régime alimentaire. La prise de nourriture hautement savoureuse, ayant une teneur élevée en sucre et en gras, active le circuit de la récompense dans le cerveau, induisant du plaisir et des émotions positives. A l’inverse, un stress aigu évoque principalement l’inconfort ou des émotions négatives, contrecarrant le comportement de recherche de plaisir. En effet, une exposition à un stress aigu entraine une réponse alimentaire anhédonique et anorexique. En revanche, le stress chronique peut induire un comportement de surconsommation, ce qui représente un processus neuroadaptatif. Plusieurs régions cérébrales sont impliquées de façon indépendante dans le traitement du stress, de la prise alimentaire ou de la récompense. Cependant, les régions qui répondent à la fois à un stress et à la récompense alimentaire sont des candidates potentielles dans la coordination de ces réponses comportementales, avec des valeurs translationnelles se rattachant aux anomalies alimentaires induites par le stress. Des études suggèrent que le septum latéral (LS) est sensible au stress et est un centre de régulation de la prise alimentaire dans le cerveau. Cependant, le rôle du LS dans la régulation de la prise alimentaire dans des conditions normales et stressantes n’est pas clair. Dans un premier temps, nous avons examiné le rôle du LS dans la consommation de sucrose chez des rats non stressés. Nous avons démontré que l’inhibition du LS par des agonistes sélectifs des récepteurs GABAA et GABAB potentialise la prise de sucrose et les paramètres de microstructure des lapements, induisant une motivation amplifiée envers la solution de sucrose chez les rats rassasiés. Ensuite, nous avons développé un modèle de surconsommation de sucrose chez le rat, et nous avons enregistré les changements dans l’activité neuronale du LS lors du passage d’une réponse anorectique induite par un stress aigu à un phénotype de surconsommation du sucrose chez des rats stressés de manière chronique. La diminution de l’expression de l’ARNm c-fos et l’augmentation de la synthèse de GABA dans le LS ont coïncidé avec l’augmentation de consommation de sucrose observée dans ce modèle. Le stress répété a augmenté la proportion de neurones inhibés par le sucrose dans le LS. De plus, l’administration de l’agoniste du récepteur GABAB restaure la diminution de consommation de sucrose induite par un stress aigu. Nous avons également étudié la réponse neuronale en temps réel de l’aire hypothalamique antérieure (AHA) qui a des connexions robustes et réciproques avec le LS et des aires hypothalamiques impliquées dans la régulation de la prise alimentaire et du stress. Dans des conditions non stressantes, la prise de sucrose a suscité des réponses inhibitrices prédominantes dans les neurones de l’AHA. Un stress aigu a augmenté le taux de décharge de ces neurones inhibés par le sucrose, amenant à une réponse anorectique envers le sucrose. Sur la base de ces résultats, nous avons conclu que le stress active, alors que la prise de sucrose inhibe, les neurones de l’AHA et du LS. Par conséquent, le LS et l’AHA sont des régions importantes impliquées dans la régulation du stress et du comportement alimentaire. Une activité neuronale aberrante dans le LS et l’AHA peut être impliquée dans les troubles alimentaires et métaboliques.Stressful and sedentary lifestyle accompanied by modern obesogenic environment, are the leading causes of diet-induced obesity and eating disorders. Intake of highly palatable food, with its high fat and sugar content, activates the reward pathways in the brain inducing pleasure and positive emotion. Conversely, acute stress primarily evokes discomfort or negative emotions counteracting with pleasure-seeking behaviour. In fact, acute stress exposure results in anorexic and anhedonic feeding response. In contrast, chronic stress may induce over-eating behaviour that represents a neuroadaptive process. Multiple brain regions are independently implicated in stress, feeding and reward processing. However, regions co-responsive to stress and food rewards are the candidates for coordinating behavioural responses with translational values pertaining to stress-induced feeding abnormalities. Studies suggest that the lateral septum (LS) is a stress-responsive and feeding regulating center of the brain. However, the role of LS in food intake regulation in normal and stressful conditions is not clear. First, we have investigated the role of LS in sucrose intake in non-stressed rats. We have demonstrated that LS inhibition by selective GABAA and GABAB receptor agonists potentiates sucrose intake and licking microstructure parameters, resulting in amplified motivation towards sucrose solution in satiated rats. Further, we have developed a sucrose bingeing model in rats, and monitored the changes in LS neural activity during transformation from acute stress-induced anorectic response to sucrose-bingeing phenotype in chronically stressed rats. Decreased c-fos mRNA and increased GABA synthesis in LS coincided with the increased sucrose intake in this model. Repeated stress increased the proportion of sucrose-inhibited neurons in the LS. Supportively, administration of a GABAB receptor agonist rescued an acute stress-induced decrease in sucrose intake. We also investigated the real-time neuronal responses of the anterior hypothalamic area (AHA) which has robust reciprocal connections with LS and the hypothalamic stress- and food intake-regulating areas. During non-stressful condition, sucrose lick clusters evoked predominant inhibitory responses in AHA neurons. Acute stress increased the firing rate of these sucrose-inhibited neurons, leading to anorectic response towards sucrose. Based on these evidences, we conclude that stress activates, whereas sucrose intake inhibits LS and AHA neurons. Therefore, the LS and AHA are important brain regions involved in regulation of stress and feeding behaviour. The aberrant neuronal activity in the LS and AHA may be involved in metabolic and eating disorders.
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Kienzle, Frederike Bianca. "Die Wirkung des 5-HT 1A-Agonisten 8-OH-DPAT auf die Serotoninfreisetzung im lateralen Hypothalamus und des Fressverhalten der Ratte". Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2002. http://dx.doi.org/10.18452/14982.
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Serotonin (5-HT) nimmt eine wichtige Rolle in der Regulation von Nahrungsaufnahme ein. Erhöhte 5-HT-Freisetzung hemmt die Nahrungsaufnahme. Der 5-HT1A-Rezeptor liegt sowohl somatodendritisch als auch postsynaptisch vor. Seine Stimulation mit 8-OH-DPAT vermindert die 5-HT-Freisetzung. Die in-vivo-Mikrodialyse ermöglichte uns eine kontinuierliche Messung von extrazellulärem 5-HT im lateralen Hypothalamus an der frei beweglichen Ratte. Unsere Ergebnisse zeigen einen Abfall der 5-HT-Freisetzung bei satten Ratten, nicht jedoch wenn diesen nach Substanzgabe Futter angeboten wurde. Bei hungrigen Ratten war nach Substanzgabe keine signifikante Veränderung in der 5-HT-Freisetzung zu messen. Zusammenfassend wird mit der vorliegenden Studie erstmals die Wirkung von 8-OH-DPAT auf die 5-HT-Freisetzung im LHA in Abhängigkeit von unterschiedlichen Motivationszuständen in Verbindung mit Nahrungsaufnahme gezeigt.Serotonin (5-HT) is an important mediator of satiety. Increase of 5-HT release inhibits food intake. 8-OH-DPAT, an agonist at the somatodendritic 5-HT1A autoreceptor, reduces serotonergic activity and induces food intake. With the technique of in vivo microdialysis we were able to measure continuously extracellular 5-HT in the lateral hypothalamic area (LHA) in freely moving rats under different feeding conditions. The present results show a decrease of 5-HT release in freely feeding rats after administration of 8-OH-DPAT. This effect was not obtained when offering food after drug application. In contrast, no significant effect in 5-HT release after application of 8-OH-DPAT in food deprived rats was measured. In summery this study demonstrates the effect of 8-OH-DPAT on the 5-HT release in LHA of freely moving rat depending on the different feeding conditions.
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FERRAND, CHRISTOPHE. "Contribution a l'identification moleculaire d'un neuropeptide revele par certains immunserums anti prolactine dans des neurones de l'hypothalamus lateral du rat". Besançon, 1994. http://www.theses.fr/1994BESA3703.
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Machado, Carla de Moraes. "Alterações na expressão do Hormônio Concentrador de Melanina (MCH) na área hipotalâmica lateral do rato ao longo do desenvolvimento pós-natal e envelhecimento /". Botucatu, 2015. http://hdl.handle.net/11449/128083.
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Orientador: José de Anchieta de Castro e Horta JuniorCoorientador: Jackson Cioni Bittencourt
Banca: Luiz Fernando Takase
Banca: Luciana Pinato
Resumo: O hormônio concentrador de melanina (MCH) do rato é um nonadecapeptídeo presente em neurônios localizados, principalmente, na área hipotalâmica lateral (LHA) que se projetam para diversas regiões do neuro-eixo. O MCH está envolvido em diversas funções, tais como: reprodução, certos aspectos do comportamento motivado, atividade locomotora, percepção sensorial, controle de temperatura, memória, aprendizagem, ansiedade, ciclo sono-vigília e comportamento alimentar. Nesse, o MCH atua como neuropeptídeo orexígeno. Durante o envelhecimento, ocorre a diminuição no consumo de energia associada à idade. Nesse trabalho, analisamos em diferentes faixas etárias, as variações da expressão do MCH na área hipotalâmica lateral, empregando métodos esterológicos (para estimar o número de neurônios MCH-ir, área, volume e densidade neuronal), reconstrução tridimensional (para estudo da distribuição dos neurônios MCH-ir) e densitometria óptica de tecido hibridizado para reconhecimento do RNAm do ppMCH (para mensuração da área hibridizada, densidade óptica média e densidade óptica integrada [DOI]) na LHA e em suas regiões. Foram utilizados 35 ratos Sprague-Dawley machos, divididos em 7 grupos experimentais de diferentes idades: 14 (lactente), 28 (pré-púbere), 50 (púbere), 90 (adulto jovem), 210 (adulto maduro), 540 (adulto senescente) e 750 (adulto senil) dias pós-natais. Os animais foram submetidos à perfusão transcardíaca, seus encéfalos coletados e processados para análise da expressão do MCH na área hipotalâmica lateral, segundo protocolos de imuno-histoquímica e hibridização in situ. A LHA apresentou um aumento significativo no número de neurônios apenas entre os grupos de 14 e 28 dias e sua área e volume foram significativamente menores apenas no grupo de 14 dias em relação a todos os grupos, com exceção do grupo de 750 dias. No entanto, com relação a densidade neuronal não foram observadas...
Abstract: The Melanin-Concentrating Hormone (MCH) is a nonadecapeptide located mainly in neurons in the lateral hypothalamic area (LHA), which innervate several regions of neuraxis. MCH is involved in many functions as reproduction, aspects of motived behaviors, motor activity, sensorial information, temperature control, memory, learning, anxiety, sleep-wake cycle and feeding behavior in which the MCH plays an orexigenic role. The energy consumption in aging is reduced as well as, the expression of MCH presents alterations associated with age. Therefore, we analyzed the variations in the expression of MCH at different ages in the lateral hypothalamic area, using stereology (to estimate the number of MCH-ir neurons, area, volume and neuronal density), 3D reconstruction (to study the distribution of MCH-ir neurons) and optical density after in situ hybridization protocol for ppMCH RNAm (to measure the hibridizated area, the mean optical density and the integrated optical density [IOD]) in the LHA and its three regions. In this study, 35 animals were divided in 7 experimental groups of 14 (neonate), 28 (prepubescent), 50 (pubescent), 90 (young adult), 210 (middle aged adult), 540 (senescent adult) and 750 (elderly adult) postnatal days. All the animals were perfused via the ascending aorta, the brains were collected and processed by immunohistochemistry and in situ hybridization protocols to analyze the expression of MCH in the lateral hypothalamic area. LHA neurons number increased only between groups of 14 and 28 days, and its area and volume significantly smaller in 14-days group when in respect to all other groups but the 750-days one. However, there weren't differences in neuronal density among groups. MCH-ir neurons distribution in LHA and contiguous regions was similar among all groups as well. Hypothalamic MCH-ir neurons has shown uniform rates in and out of LHA, but after analyzing its distribution in mamillary, tuberal and anterior ...
Mestre
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Machado, Carla de Moraes [UNESP]. "Alterações na expressão do Hormônio Concentrador de Melanina (MCH) na área hipotalâmica lateral do rato ao longo do desenvolvimento pós-natal e envelhecimento". Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/128083.
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O hormônio concentrador de melanina (MCH) do rato é um nonadecapeptídeo presente em neurônios localizados, principalmente, na área hipotalâmica lateral (LHA) que se projetam para diversas regiões do neuro-eixo. O MCH está envolvido em diversas funções, tais como: reprodução, certos aspectos do comportamento motivado, atividade locomotora, percepção sensorial, controle de temperatura, memória, aprendizagem, ansiedade, ciclo sono-vigília e comportamento alimentar. Nesse, o MCH atua como neuropeptídeo orexígeno. Durante o envelhecimento, ocorre a diminuição no consumo de energia associada à idade. Nesse trabalho, analisamos em diferentes faixas etárias, as variações da expressão do MCH na área hipotalâmica lateral, empregando métodos esterológicos (para estimar o número de neurônios MCH-ir, área, volume e densidade neuronal), reconstrução tridimensional (para estudo da distribuição dos neurônios MCH-ir) e densitometria óptica de tecido hibridizado para reconhecimento do RNAm do ppMCH (para mensuração da área hibridizada, densidade óptica média e densidade óptica integrada [DOI]) na LHA e em suas regiões. Foram utilizados 35 ratos Sprague-Dawley machos, divididos em 7 grupos experimentais de diferentes idades: 14 (lactente), 28 (pré-púbere), 50 (púbere), 90 (adulto jovem), 210 (adulto maduro), 540 (adulto senescente) e 750 (adulto senil) dias pós-natais. Os animais foram submetidos à perfusão transcardíaca, seus encéfalos coletados e processados para análise da expressão do MCH na área hipotalâmica lateral, segundo protocolos de imuno-histoquímica e hibridização in situ. A LHA apresentou um aumento significativo no número de neurônios apenas entre os grupos de 14 e 28 dias e sua área e volume foram significativamente menores apenas no grupo de 14 dias em relação a todos os grupos, com exceção do grupo de 750 dias. No entanto, com relação a densidade neuronal não foram observadas...
The Melanin-Concentrating Hormone (MCH) is a nonadecapeptide located mainly in neurons in the lateral hypothalamic area (LHA), which innervate several regions of neuraxis. MCH is involved in many functions as reproduction, aspects of motived behaviors, motor activity, sensorial information, temperature control, memory, learning, anxiety, sleep-wake cycle and feeding behavior in which the MCH plays an orexigenic role. The energy consumption in aging is reduced as well as, the expression of MCH presents alterations associated with age. Therefore, we analyzed the variations in the expression of MCH at different ages in the lateral hypothalamic area, using stereology (to estimate the number of MCH-ir neurons, area, volume and neuronal density), 3D reconstruction (to study the distribution of MCH-ir neurons) and optical density after in situ hybridization protocol for ppMCH RNAm (to measure the hibridizated area, the mean optical density and the integrated optical density [IOD]) in the LHA and its three regions. In this study, 35 animals were divided in 7 experimental groups of 14 (neonate), 28 (prepubescent), 50 (pubescent), 90 (young adult), 210 (middle aged adult), 540 (senescent adult) and 750 (elderly adult) postnatal days. All the animals were perfused via the ascending aorta, the brains were collected and processed by immunohistochemistry and in situ hybridization protocols to analyze the expression of MCH in the lateral hypothalamic area. LHA neurons number increased only between groups of 14 and 28 days, and its area and volume significantly smaller in 14-days group when in respect to all other groups but the 750-days one. However, there weren't differences in neuronal density among groups. MCH-ir neurons distribution in LHA and contiguous regions was similar among all groups as well. Hypothalamic MCH-ir neurons has shown uniform rates in and out of LHA, but after analyzing its distribution in mamillary, tuberal and anterior ...
FAPESP: 2013/08618-3
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Vercruysse, Pauline. "Altérations hypothalamiques dans la sclérose latérale amyotrophique". Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ064/document.
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La Sclérose Latérale Amyotrophique (SLA) est une maladie neurodégénérative due à la dégénérescence des motoneurones supérieurs et inférieurs. La perte des neurones moteurs entraine une atrophie puis une paralysie progressive des muscles. En plus de la perte musculaire, une perte de poids est importante chez les patients SLA. Ce symptôme apparaît avant les premiers symptômes moteurs et est corrélé avec la survie. Ce défaut du métabolisme énergétique est en partie dû à un hypermétabolisme associé à des problèmes de prise alimentaire. L’hypothalamus est la partie du cerveau contrôlant l’ensemble du métabolisme énergétique. L’objectif de ma thèse a été de caractériser les altérations hypothalamiques dans la SLA. Nous avons tout d’abord mis en évidence une anomalie du système mélanocortine de l’hypothalamus, et montré que cette anomalie était associée à des modifications du comportement alimentaire. Ensuite, nos travaux ont mis en évidence une atrophie de la partie postérieure de l’hypothalamus, comprenant l’aire hypothalamique latérale (LHA), des patients SLA, corrélée à la perte de poids. Finalement, nous démontré que les neurones produisant le MCH, situés dans le LHA, sont atteints dans la SLA et qu’une complémentation en MCH empêche la perte de poids dans un modèle animal de SLAAmyotrophic Lateral Sclerosis (ALS) is a major neurodegenerative disease characterised by a loss of upper and lower motor neurons. The loss of motor neurons leads to muscle atrophy and paralysis. Besides motor loss, weight loss is important in ALS patients. This symptom appears before first muscular symptoms and is correlated with survival. This defect of energetic metabolism is partially due to hypermetabolism associated with food intake problems. Hypothalamus is the part of brain controlling the energetic metabolism. The aim of my Ph.D. was to characterise hypothalamic alterations in ALS. First, we have shown a default in the melanocortin system of hypothalamus, and shown that this melanocortin defect correlates with alterations in food intake behaviour. Second, we demonstrated the existence of hypothalamic atrophy in ALS patients in the posterior part of the hypothalamus, including the lateral hypothalamic area (LHA). This atrophy was correlated with weight loss. Finally, we observed that hypothalamic MCH neurons, located in the LHA, are affected in ALS, and that MCH complementation rescues weight loss in a mouse model of ALS
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Ferreira, Jozélia Gomes Pacheco. "Organização das projeções da área tegmental ventral para o complexo VTA-substância negra e para o hipotálamo no rato e estudo da expressão dos substratos do receptor de insulina em neurônios da VTA que se projetam para o estriado". Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42137/tde-25032010-144241/.
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Numa primeira etapa, estudamos as conexões da VTA para o complexo VTA-substância negra (SN) utilizando a leucoaglutinina do Phaseolus vulgaris (PHA-L). Estas conexões são substanciais, topograficamente organizadas, com destaque para o pólo caudal da VTA que inerva bilateralmente toda a extensão deste complexo. Numa segunda etapa, estudamos as projeções da VTA para o hipotálamo. A VTA se projeta principalmente para a área pré-óptica lateral e área hipotalâmica lateral, a região subfornical posterior e o núcleo dorsomedial. Foram vistas poucas aposições entre varicosidades PHA-L+ e neurônios imunorreativos para orexina ou para hormônio concentrador de melanina. Por fim, estudamos a colocalização do substrato do receptor de insulina (IRS-1), IRS-1 fosforilado e fosfatidilinositol-3 quinase (PI3K) com tirosina hidroxilase (TH) ou com a subunidade B da toxina colérica (CTb) injetada no estriado. A maioria dos neurônios TH+ da VTA-SN expressa IRS-1; injeções de CTb no estriado resultaram em células duplamente marcadas para CTb/IRS-1, CTb/PI3K e CTb/IRS-1 fosforilado.In a first step, we studied the connections of the VTA to the complex VTA-substantia nigra (SN) using the Phaseolus vulgaris leucoagglutinin (PHA-L). These connections are substantial, topographically organized, especially the caudal pole of the VTA, which innervates bilaterally throughout the length of this complex. In a second step, we studied the projections of the VTA to the hypothalamus. The VTA projected mainly to the lateral preoptic area, lateral hypothalamic area, posterior subfornical region and dorsomedial nucleus. Were observed few appositions between PHA-L+ varicosities and neurons immunoreactive for orexin or melanin-concentrating hormone. Finally, we studied the co-localization of the insulin receptor substrate-1 (IRS-1), IRS-1-phosphorylated and phosphatidylinositol-3 kinase (PI3K) with tyrosine hydroxylase (TH) or cholera toxin B subunit (CTb) injected into the striatum. Most TH+ neurons of the VTA-SN expressed IRS-1; CTb injections in the striatum resulted in cells double-labeled for CTb/IRS-1, CTb/PI3K and CTb/IRS-1 phosphorylated.
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David, Richard Boarato. "Natriorexigênese paradoxal: núcleo parabraquial lateral e mecanismos centrais, sistêmicos e comportamentais". Universidade Federal de São Carlos, 2013. https://repositorio.ufscar.br/handle/ufscar/1246.
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Previous issue date: 2013-03-22Sodium intake is induced by facilitatory signals, like angiotensin II and aldosterone Cell dehydration, a classical inhibitory signal for sodium intake, may also induce paradoxical sodium intake if the sodium intake inhibition by the ocitocinergic hypothalamic mechanism or by the lateral parabraquial nucleus (LPBN) is absent. Thus, the LPBN deactivation could modify the activity of hypothalamic oxytocinergic pathways or the gastric emptying control system, another inhibitory system, as well as facilitatory areas and the reward system. The aim of this study was to investigate the effect of LPBN injections of methysergide (4 μg/0.2 μl, serotonergic antagonist) in cell dehydrated animals on: activity of brain areas involved in ingestive behavior by measuring c-Fos protein immunoreactivity and tissue levels of dopamine, serotonin and metabolites or plasma hormone levels; pre-systemic satiety involving gastric emptying; selectivity of paradoxical sodium intake. The effect of disinhibition of the natriorexigenesis on the reward system was tested by repeated deactivations of the LPBN with muscimol (2 nmol/0.2 μl; GABAA agonist) and its effect on ingestive behavior sensitization and water deprivation with partial rehydration followed by sodium access (WD-PR protocol) on the lateral hypothalamus self-stimulation (LHSS). Holtzman or Sprague-Dawley rats (280-320 g), intacts or operated (femoral vein cannulation and/or guide cannulas implanted in direction to the LPBN or bipolar electrode implanted in the hypothalamus), were used in the experiments. Animals treated with methysergide and hyperosmotic by gavage of 2 M NaCl (2 ml) compared to the control treatment (vehicle) showed: (a) increase in ir-Fos in the area postrema and intermediate nucleus of the solitary tract, subfornical organ and non-oxytocinergic neurons of the ventral portion of the paraventricular nucleus of the hypothalamus; (b) increase in tissue levels of dopamine in the amygdala, but not in the accumbens; (c) unchanged activity of oxytocinergic system (ir-Fos in oxytocinergic neurons and oxytocin plasma levels similar to control group). Hyperosmotic rats (iv infusion of 2 ml of 2 M NaCl) treated with methysergide and a gavage of 0.3 M NaCl (3 ml) showed a hypertonic gastric and intestinal content similar to the control group (vehicle) after gavage. In hydrated animals with a history of two previous treatments of muscimol into the LPBN, the hypertonic NaCl intake induced by muscimol was higher than the control animals pretreated with vehicle. The LHSS was not altered at any stage of WD-PR protocol, as well as in cell dehydrated animals in comparison with hydrated control group. The results demonstrate that the deactivation of the LPBN enhances specifically the intake of solutions containing sodium and suggest the involvement of the brain stem and the amygdala during the appetitive phase of the paradoxical sodium intake, while the deactivation of other inhibitory mechanisms (oxytocin and gastric retention) seems not to be essential. Furthermore, the repetition of LPBN deactivation sensitizes hydrated animals for sodium intake. Removing the inhibition of sodium appetite by partial rehydration in WD-PR does not change the LHSS reward.
A ingestão de sódio é induzida por sinais facilitadores, como a angiotensina II e a aldosterona. Apesar de classicamente considerada antinatriorexigênica, a desidratação celular também se mostra facilitadora da ingestão paradoxal de sódio quando a inibição da ingestão de sódio pelo mecanismo ocitocinérgico do hipotálamo ou pelo núcleo parabraquial lateral (NPBL) está desativada. A desativação do NPBL poderia, então, atuar sobre o mecanismo ocitocinérgico ou de controle do esvaziamento gástrico, ambos inibidores, ou ainda modificar a atividade de áreas facilitadoras ou envolvidas na recompensa. O objetivo deste estudo foi investigar o efeito da injeção de metisergida (4 μg/0,2 μl, antagonista serotonérgico) no NPBL em animais com desidratação celular sobre a: atividade de áreas encefálicas envolvidas no comportamento ingestivo, medindo-se imunorreatividade para proteína c-Fos e dosagem tecidual de dopamina, serotonina e metabólitos em áreas de interesse ou dosagem hormonal; saciedade pré-sistêmica envolvendo esvaziamento gástrico; seletividade da ingestão paradoxal de sódio. Também foi avaliado o possível efeito da desinibição da natriorexigênese sobre o sistema de recompensa através da sensibilização por desativações repetidas do NPBL pelo muscimol (2 nmol/0,2 μl; agonista GABAA) e na privação hídrica com reidratação parcial e posterior acesso ao sódio (modelo PH-RP) sobre a autoestimulação elétrica do hipotálamo lateral (AEHL). Ratos (280-320 g) Holtzman ou Sprague-Dawley, intactos ou operados (canulação da veia femoral e/ou cânulas-guia direcionadas ao NPBL ou eletrodo bipolar no hipotálamo), foram utilizados nos experimentos. Animais tratados com metisergida e hiperosmóticos por gavagem de NaCl 2 M (2 ml) apresentaram, em relação ao tratamento controle (veículo): (a) aumento da ir-Fos na área postrema e núcleo do trato solitário intermediário, no órgão subfornical e em neurônios não ocitocinérgicos da porção ventral do núcleo paraventricular do hipotálamo; (b) aumento da concentração tecidual de dopamina na amígdala, mas não no accumbens; (c) atividade do sistema ocitocinérgico inalterada (ir-Fos em neurônios ocitocinérgicos e ocitocina plasmática semelhantes ao controle). Ratos tratados com metisergida e hiperosmóticos por infusão iv de NaCl 2 M (1,5 ml), que receberam uma gavagem de NaCl 0,3 M (3 ml) apresentaram conteúdo gástrico e intestinal hipertônico semelhantes ao controle (veículo) após a gavagem. Em animais hidratados com histórico de dois tratamentos prévios de muscimol no NPBL, a ingestão de NaCl hipertônico induzida por muscimol foi superior aos animais controle tratados previamente com veículo. A AEHL não foi alterada em nenhuma fase do protocolo PH-RP, assim como em animais com desidratação celular, em relação aos controles hidratados. Os resultados demonstram que a desativação do NPBL potencializa especificamente a ingestão de solução contendo sódio e sugerem a participação do tronco encefálico e da amígdala na fase apetitiva da ingestão paradoxal de sódio, enquanto a desativação de outros mecanismos inibidores (ocitocina e retenção gástrica) parece não ser essencial. Ainda, a repetição da desativação do NPBL sensibiliza a ingestão de sódio em animais hidratados. A remoção da inibição ao apetite ao sódio pela reidratação parcial na PHRP não altera a recompensa na AEHL.
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Rufino, Rodrigo de Andrade. "Investigação da substância cinzenta periaquedutal (PAG) na organização das respostas de defesa frente ao predador". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-09082016-103424/.
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Primeiramente, investigamos as respostas defensivas de animais lesionados da parte dorsal da PAG rostral durante o confronto predatório. Estes animais permaneciam com as respostas de avaliação de risco (AR) porem perdem as respostas de freezing. Em um segundo estudo, analisamos as respostas defensivas frente ao predador em animais lesionados da parte ventrolateral da PAG caudal. Estes animais perdem as respostas de freezing e aumentam as respostas de AR. Será que as respostas de AR dependem da integridade da parte dorsal rostral e ventrolateral caudal da PAG ? Por último, investigamos as respostas defensivas em animais com lesão combinada destas áreas. Observamos uma diminuição drástica das AR e um aumento das respostas exploratórias. Provavelmente, as respostas de AR estão sendo moduladas pela parte dorsal rostral e ventrolateral caudal da PAG através de seus alvos ascendentes hipotalâmicos, e estes com o septo lateral. As respostas de freezing parecem ser moduladas por projeções descendentes da PAG para a medula espinal.First, we investigated the defensive responses of injured animals of the dorsal part of the rostral PAG during predatory confrontation. These animals remained with the risk assessment responses (AR) however lose the freezing of response. In a second study, we analyzed the defensive responses front predator injured animals in the ventrolateral part of the caudal PAG. These animals lose the responses of freezing and increase AR responses. Does the AR responses depend on the integrity of dorsal part rostral and caudal ventrolateral PAG? Finally, we investigated the defensive responses in animals with combined injury of these areas. We observed a dramatic decrease of AR and an increase in exploratory response. Probably AR responses are modulated by the dorsal part of the rostral and caudal ventrolateral PAG through its hypothalamic ascendant targets, and these with the lateral septum. Freezing responses appear to be modulated by descending projections from the PAG to the spinal cord.
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Machado, Carla de Moraes. "Efeito da restrição alimentar materna durante a prenhez e lactação nos neurônios MCH e CART da área hipotalâmica lateral (LHA)". Botucatu, 2019. http://hdl.handle.net/11449/181860.
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Orientador: José de Anchieta de Castro e Horta JúniorResumo: A associação do baixo peso ao nascer com alto risco de doenças como obesidade, diabete tipo 2 e doenças cardiovasculares na vida adulta levaram à hipótese da “Origem Desenvolvimentista da Saúde e Doença” (DOHaD). Nessa hipótese, Programação se refere às adaptações executadas pelo organismo frente a insultos ocorridos durante seu desenvolvimento, gerando efeitos permanentes ou não na estrutura e função de órgãos. A nutrição materna durante o desenvolvimento do indivíduo é considerada um importante indutor de Programação, visto que a deficiência de nutrientes, durante a prenhez e a lactação, provoca alterações significativas no peso corpóreo, no balanço energético, na ingestão alimentar e na expressão de neuropeptídeos. O hormônio concentrador de melanina (MCH) e o transcrito regulado pela cocaína e anfetamina (CART) são neuropeptídeos expressos na área hipotalâmica lateral (LHA), que participam da regulação do balanço energético e do comportamento alimentar, nos quais o MCH desempenha papel orexígeno e o CART, anorexígeno. Nosso objetivo foi analisar o número e a distribuição de neurônios MCH e CART e sua ultraestrutura na LHA de ratos cujas mães foram submetidas à restrição alimentar durante a prenhez e lactação. Fêmeas prenhes Wistar foram separadas em dois grupos experimentais: grupo controle (GC), dieta padrão ad libitum, e grupo restrição calórica (GR), dieta de 50% de restrição em relação ao grupo controle durante os períodos de prenhez e lactação. Foram avaliados o núme... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The association between lower birth weight and an increased risk of obesity, diabetes type 2 and cardiovascular diseases in adult life led to Developmantal Origins of Health and Disease (DOHaD) hypothesis. In this hypothesis, programming is related to the adjustments performed by the organism to insults occurring at key stages of their development, which may lead to long-lasting effects in the organs structure and function. Maternal nutrition during critical periods of individual development is considered an important Programming inductor, since the nutrient deficiency during pregnancy and lactation causes significant changes in body weight, energy balance, food intake and neuropeptides expression. The melanin-concentrating hormone (MCH) and the cocaine- and amphetamine-regulated transcript (CART) are neuropeptides expressed in the lateral hypothalamic area (LHA) that are involved in the regulation of energy balance and feeding behavior in which MCH plays an orexigenic role and CART an anorexigenic one. Thus, our aim was to analyze the number and the distribution of MCH and CART and the ultrastructure of these neurons in the LHA of rats whose mothers were subjected to food restriction during pregnancy and lactation. After pregnancy confirmation, female Wistar rats were divided in two groups: control group (CG), ad libitum standard diet, and caloric restriction group (RG), 50% diet restriction compared to the control group during pregnancy and lactation. After birth, the numbe... (Complete abstract click electronic access below)
Doutor
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Lai, Yu-Ting. "The effect of prenatal stress exposure on cognitive function in later life in rats". Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25876.
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Prenatal stress exposure (PNS) has detrimental effects on the offspring’s brain and behaviour and has been identified as an etiological factor in inducing cognitive function deficits in rodents and humans. The neural mechanisms are unclear, however reprogramming of the neuroendocrine stress axis, the hypothalamo-pituitary- adrenal (HPA) axis is hypothesised. A psychosocial stressor (residentintruder paradigm) was used to generate PNS rat offspring, making these studies clinically compatible. The hippocampus and the medial prefrontal cortex (mPFC) are critical in regulating cognitive function and also contribute to the negative feedback control of the HPA axis via corticosteroid receptors, including the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Here the Barnes maze was used to assess spatial learning and memory in male and female PNS offspring during adulthood under different scenarios, including basal and acute and chronic stress conditions. Under basal conditions, PNS was associated with reduced GR and MR mRNA expression in the medial prefrontal cortex (mPFC) and the hippocampus, respectively; suggesting inhibitory feedback control of the HPA axis may be compromised in PNS rats. Moreover, impaired spatial learning was observed in male PNS rats following acute restraint stress. Bilateral lesions of the prelimbic cortex and central administration of an MR antagonist in control rats suggested acute stress-induced learning deficits in PNS males were a result of impaired hippocampus-mediated inhibitory feedback control of the HPA axis. Conversely, a one-week variable stress regimen facilitated spatial learning in PNS rats and this was associated with elevated MR mRNA expression in the dentate gyrus. Moreover, facilitated learning in the PNS rats exposed to chronic stress could be blocked by central administration of an MR antagonist, indicating a facilitatory role of hippocampal MR in spatial learning. In summary, opposite effects of PNS on spatial learning were observed under acute and chronic stress conditions, in which hippocampal MR played a key role in regulating behavioural performance. The effect of age was also examined in PNS rats, and the findings from middle-aged (10-11 months old) rats indicated PNS may accelerate cognitive decline. Sex differences were also studied, with control females’ out-performing males under basal conditions in terms of spatial learning and behavioural flexibility; however following prenatal or chronic stress these sex differences were no longer detected. Furthermore, acute stress impaired spatial learning to a greater extent in females, and this might be attributed to greater HPA axis responses to stress in females compared with males. In conclusion, prenatal stress alters later cognitive performance, in a sex- and stress context-dependent manner. Hippocampal MR plays a critical role in mediating spatial learning, particularly during stress conditions.
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Kienzle, Frederike Bianca. "Die Wirkung des 5-HT1A-Agonisten 8-OH-DPAT auf die Serotoninfreisetzung im lateralen Hypothalamus und das Fressverhalten der Ratte eine In-vivo-Mikrodialyse-Studie /". [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=970018193.
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Oliveira, Wagner Fernandes de. "Análise da participação da porção rostrolateral da substância cinzenta periaquedutal (PAGrl) no comportamento de busca por droga". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-07122015-152245/.
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O córtex pré-frontal (PFC) participa do controle do comportamento de busca por droga e se projeta para a coluna rostrolateral da substância cinzenta periaquedutal (PAGrl) que por sua vez se projeta para o sistema orexinérgico da área hipotalâmica lateral (LHA) que controla comportamentos que oferecem recompensa através de projeções para o sistema dopaminérgico mesolímbico. O objetivo do trabalho é investigar a participação da PAGrl e a sua relação com o PFC e com o sistema orexinérgico da LHA na expressão do comportamento de busca por droga. Submetemos ratos Wistar ao condicionamento de preferência por lugar para sulfato de morfina e notamos que o PFC, a PAGrl e a LHA estão ativados em animais que expressaram tal comportamento. Após, realizamos lesões neuroquímicas bilaterais no PFC e notamos a ausência da busca pela droga nestes animais e da diminuição da ativação da PAGrl e do sistema orexinérgico da LHA. Posteriormente realizarmos lesões neuroquímicas por NMDA na PAGrl e notamos a ausência do comportamento e diminuição de duplas marcações para Fos e orexina na LHA. Os resultados indicam que a PAGrl exerceria um papel crítico para o comportamento de busca por droga, integrando aferências provenientes do PFC para modular os neurônios orexinérgicos da LHA.The prefrontal cortex (PFC) is involved with planning of the drug seeking behavior and projects itself to the rostrolateral periaqueductal gray (PAGrl) that through projections for the orexin neurons in the lateral hypothalamic area (LHA), participates in the control of behavior that offer rewards. The LHA controls drug reward through projections for the mesolimbic dopaminergic system. This study aims to investigate the relationship between the PFC, PAGrl and orexin neurons in the LHA in drug seeking behavior. We did a morphine conditioned place preference (CPP) procedure in intact, bilateral PAGrl-lesioned and bilateral PFC-lesioned Wistar rats and investigated the pattern of Fos expression. The intact animals displayed such behavior and presented an increase in Fos activation in the PFC, rlPAG and LHA orexinergic neurons. Conversely, PAGrl-lesioned and PFC-lesioned animals did not display this behavior and reduced the activation of orexin neurons in the LHA. PFC-lesioned animals presented a reduction of the Fos activation in the rlPAG. The results suggest a pathway involving the PFC, PAGrl and LHA orexinergic cell group underlying the CCP, where the rlPAG would integrate inputs from the PFC to control the LHA orexinergic cell group.
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Flora, Brunella Valbão. "Investigação dos neurônios da porção rostrolateral da substância cinzenta periaquedutal (PAGrl) mobilizados durante a busca por droga e suas conexões com o córtex pré-frontal medial (mPFC) e neurônios orexinérgicos da área hipotalâmica lateral (LHA)". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-09112016-093236/.
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Estudos apontam a substância cinzenta periaquedutal (PAG) como um sítio crítico para a expressão de vários comportamentos motivados. A porção rostrolateral da PAG (PAGrl), tem um papel chave na regulação da motivação na caça predatória, e modularia mecanismos de recompensa associados ao comportamento alimentar e busca por droga, a partir de projeções para área tegmental ventral e núcleo acumbens; o que dependeria da ligação com neurônios orexinérgicos da área hipotalâmica lateral (LHA). A PAGrl, está mobilizada nos comportamentos de busca por droga assim como na caça predatória. As principais regiões que aferentam a PAGrl são áreas do córtex pré-frontal medial (mPFC) onde a PAGrl integraria tais aferencias e modularia a LHA. Os resultados corroboram com a hipótese, pois lesões no mPFC diminuíram a busca por droga e vimos que neurônios da PAGrl mobilizados no comportamento, que recebem aferências do mPFC, seriam os mesmos que se projetam para LHA e que a PAGrl teria papel crítico na promoção do comportamento de busca por droga no CPP para sulfato de morfina.Studies show a periaqueductal gray (PAG) as a critical place for an expression of motivated behaviors. The rostrolateral portion of PAG (PAGrl), is a key role in the regulation of motivation in predatory hunting, and modulates, reward mechanisms associated with drug and food seeking, through projections to ventral tegmental area and the nucleus accumbens; what would depend on the connection with orexin neurons of the lateral hypothalamic area (LHA). The PAGrl, is mobilized in predatory hunting as drug seeking. The main region that sends projections to PAGrl is the medial prefrontal cortex (mPFC), where PAGrl integrate such afferent and modulates the LHA. Our results corroborate the hypothesis, because mPFC injuries, decreased drug seeking and we observed that PAGrl neurons mobilized in behavior, and also receive afferents from mPFC, would be the same as projecting to LHA, thus PAGrl had critical role in promotion of drug seeking behavior during the CPP for morphine sulfate.
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Kienzle, Frederike Bianca [Verfasser], H. [Gutachter] Jarry, med R. [Gutachter] Morgenstern y N. C. [Gutachter] Juhr. "Die Wirkung des 5-HT 1A-Agonisten 8-OH-DPAT auf die Serotoninfreisetzung im lateralen Hypothalamus und des Fressverhalten der Ratte / Frederike Bianca Kienzle ; Gutachter: H. Jarry, med.R. Morgenstern, N.-C. Juhr". Berlin : Humboldt-Universität zu Berlin, 2002. http://d-nb.info/1207668567/34.
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Chometton, Sandrine. "Organisation morphofonctionnelle de l'hypothalamus latéral postérieur chez le rongeur". Thesis, Besançon, 2015. http://www.theses.fr/2015BESA2016/document.
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L'hypothalamus latéral (LHA) est impliqué dans un grand nombre de fonctions dont les principales sont la régulation du métabolisme énergétique et des états de vigilance. L'objectif de ce travail est de caractériser les grandes divisions du LHA et d'analyser leur implication dans le cycle veille / sommeil et la prise alimentaire. Une comparaison de la distribution de différents marqueurs hypothalamiques révélés par immunohistochimie ou hybridation in situ a permis de mettre en évidence cinq domaines dans le LHA. L'implication de chacun des domaines dans des conditions expérimentales liées aux états d'éveil ou à la prise alimentaire a été définie à partir de l'expression d'un marqueur d'activation neuronale, la protéine c-Fos. LeLHA antérieur et le LHA tubéral, chacun divisé en deux domaines rostral et caudal, sont composés de neurones localisés de manière diffuse et sont impliqués dans les phénomènes d'activation générale du système nerveux central. Le LHA mamillaire est renommé LHA prémamillaire à partir de l'étude de la distribution des ARNm GAD et préprotachykinine, et est composé de différents noyaux caractérisés par l'expression de marqueurs spécifiques.Parmi eux, les noyaux parasousthalamique (PSTN) et calbindine (CbN) sont activés lors d'exposition à des goûts de valeur hédonique positive. Les analyses hodologiques ont montré que ce complexe nucléaire reçoit des projections CGRP du noyau parabrachial et projette dansle noyau central de l'amygdale. Il est également connecté avec le cortex insulaire. Ces différentes structures sont impliquées dans les circuits de la gustation et de la récompense. Le PSTN et le CbN sont donc intégrés dans différentes voies de régulation du comportement de prise alimentaire. Enfin, les données morpho fonctionnelles obtenues pour le LHA sont mises en relation avec des réseaux impliquant diverses structures cérébrales telles que le télencéphale basal, le thalamus ou le mésencéphaleThe lateral hypothalamic area (LHA) is involved in many functions, but mainly in food intakeor sleep / wake cycle regulation. The aim of this study is to characterize the main regions inthe LHA and to analyze their involvement in the sleep / wake cycle and food intake. Acomparison of the distribution of different hypothalamic markers labeled byimmunohistochemistry or in situ hybridization highlights five domains in the LHA. Theimplication of each domain in different experimental conditions linked to arousal or foodintake is analyzed by studying the expression of the c-Fos protein as a neuronal activationmarker. Neurons in the anterior and tuberal LHA, both divided into rostral and caudaldomains, are distributed in a diffuse way and are activated under arousal conditions. Themammillary LHA, renamed the premammillary LHA on the basis of GAD andpreprotachykinin mRNA expression, is composed of several nuclei characterized by specificmarker expression. Among them, the parasubthalamic nucleus (PSTN) and the calbindinnucleus (CbN) are activated by ingestion of compounds with a positive taste. Theconnectional analysis showed that these two structures receive CGRP projections from theparabrachial nucleus and projects into the central nucleus of the amygdala. The PSTN / CbNcomplex is also connected with the insular cortex. These different structures are known to beinvolved in gustatory and reward circuitries; the PSTN and the CbN are thus integrated innetworks controlling the food intake behavior. Finally, the morphofunctional data obtainedfor the LHA demonstrate that this region is connected to other networks involving variouscerebral structures such as the basal telencephalon, the thalamus or the mesencephalon
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TESORIERO, Chiara. "Sleep and infections". Doctoral thesis, 2016. http://hdl.handle.net/11562/939133.
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L’organismo è costantemente esposto all’aggressione di patogeni che causano infezioni acute e/o croniche. La sonnolenza (ipersonnia) è un sintomo comune nel corso di infezioni, come componente del cosiddetto "sickness behavior" (“comportamento di malattia”), mirato a facilitare la guarigione. Alterazioni del sonno, della veglia e della loro alternanza possono, tuttavia, avere caratteristiche specifiche nel corso di determinate infezioni. E’ questo il caso delle infezioni causate dal parassita Trypanosoma brucei, l’agente eziologico della tripanosomiasi africana o malattia del sonno. Nel corso di tale patologia sono state infatti documentate, sia nell’uomo che in modelli sperimentali in roditori, alterazioni del ritmo sonno-veglia e della struttura del sonno, incluse alterazioni neurofisiologiche di tipo narcolettico. D’altro canto, è stato recentemente riportato, in vari paesi, un aumento di narcolessia, una rara patologia del sonno, in seguito a epidemie influenzali e tale aumento è stato ascritto a meccanismi autoimmunitari. In questa tesi di dottorato sono stati utilizzati modelli murini di infezione del virus influenzale H1N1 e del parassita Trypanosoma brucei allo scopo di indagare e verificare aspetti patogenetici, circuiti neuronali e mediatori infiammatori coinvolti nelle alterazioni del sonno e della veglia in queste malattie. L’infezione influenzale ha costituito l’oggetto del primo studio presentato nella tesi. In particolare, la sperimentazione è stata mirata a verificare se il virus influenzale H1N1 potesse causare di per sé alterazioni di tipo narcolettico in assenza di risposte autoimmuni. A tale scopo, è stata adottata un’instillazione nasale (che mima l’infezione naturale per via aerea) del ceppo virale murino di influenza A (A/WSN/33) in topi Rag1-/-, privi di risposta immunitaria adattativa. Va qui ricordato che, in condizioni fisiologiche, il sonno è caratterizzato da un'alternanza ciclica di fasi non-REM (NREM) e REM. Nel modello murino di infezione influenzale qui indagato sono stati osservati, nel corso della quarta settimana di infezione, una frammentazione delle fasi di sonno e di veglia, così come alterazioni della sequenza del sonno NREM-sonno REM rappresentate da episodi “sleep-onset REM” (SOREM). Negli episodi SOREM il sonno REM è preceduto da un periodo di veglia invece che da un periodo di sonno NREM. Con metodiche di biologia molecolare, è stata, inoltre, documentata nell’encefalo, in seguito all’infezione, una “up-regolazione” di trascritti codificanti per mediatori pro-infiammatori. A livello cellulare, analisi immunoistochimiche mirate a identificare la localizzazione dell’antigene virale hanno rivelato che dalla cavità nasale (e, in particolare, dalla mucosa olfattiva) il virus aveva infettato il bulbo olfattivo, e da lì, presumibilmente in seguito a trasporto assonale retrogrado, neuroni in varie regioni encefaliche collegate al bulbo olfattivo. Fra questi, sono stati identificati neuroni infetti nell'ipotalamo e nel tronco encefalico, in gruppi neuronali coinvolti nella regolazione del sonno e della veglia. In particolare, nell’ipotalamo, è stato osservato, con metodiche di doppia immunofluorescenza, che il virus aveva infettato neuroni dell’ipotalamo laterale contenenti il peptide orexina/ipocretina. Questa osservazione è di particolare interesse poiché è ben documentato che i neuroni orexinergici giocano, in condizioni normali, un ruolo chiave nel mantenimento di un periodo stabile di veglia e nelle transizioni fra il sonno e la veglia e fra il sonno REM e il sonno NREM. Va, inoltre, ricordato, che i neuroni orexinergici vanno incontro a degenerazione, nell’uomo, nella narcolessia con cataplessia. Nel loro complesso, i dati sperimentali qui presentati hanno dimostrato alterazioni di tipo narcolettico nel corso di infezione influenzale e in assenza di risposte autoimmuni, richiamando l’attenzione su possibili effetti diretti dell’infezione in soggetti geneticamente predisposti. L’esistenza di proiezioni monosinaptiche di neuroni ipotalamici orexinergici al bulbo olfattivo è stata, quindi, verificata nel secondo studio sperimentale della tesi. A tal fine, è stato utilizzato un tracciante fluorescente che viene trasportato lungo gli assoni in via retrograda, il Fluoro-Gold. Il fenotipo orexinergico di una parte dei neuroni marcati in via retrograda dal tracciante nell’ipotalamo è stato verificato con metodiche di doppia marcatura. Con questo approccio metodologico è stata così dimostrata, per la prima volta, l’esistenza di una proiezione diretta dei neuroni orexinergici al bulbo olfattivo. Tale via neurale può, quindi, venire utilizzata da patogeni e agenti tossici ambientali per raggiungere centri ipotalamici che svolgono un ruolo chiave nella regolazione del sonno e della veglia. Il terzo studio della tesi si è focalizzato sulla tripanosomiasi africana. Sia nell’uomo che nell’animale da esperimento l’infezione evolve in due stadi: un primo stadio emolinfatico, seguito da uno stadio meningo-encefalitico quando il parassita invade il sistema nervoso centrale attraversando la barriera emato-encefalica. La determinazione dello stadio della malattia, che è fatale se non curata, ha importanti implicazioni terapeutiche. Tuttavia, i criteri attualmente in uso per la diagnosi di stadio non sono sufficientemente sensibili e sono oggetto di molte critiche. Lo studio sperimentale qui presentato era mirato alla verifica di due potenziali biomarcatori dell’inizio del secondo stadio della malattia: i livelli liquorali della chemochina CXCL10 e le alterazioni del sonno e della veglia. In ratti infettati con il parassita Trypanosoma brucei brucei, il primo parametro è stato indagato mediante ELISA su campioni di siero e liquor e il secondo parametro mediante registrazione neurofisiologica continua con telemetria. I risultati dello studio, focalizzati sull’intervallo temporale durante il quale il parassita inizia ad invadere il parenchima encefalico, hanno dimostrato un picco dei livelli di CXCL10 nel siero durante la “neuroinvasione” iniziale ed un picco liquorale nella fase immediatamente successiva della malattia. I dati neurofisiologici hanno dimostrato una frammentazione progressiva delle fasi di veglia e di sonno, con un’iniziale “inversione di fase” (invasione del periodo di sonno da parte della veglia) in corrispondenza temporale con l’attraversamento della barriera emato-encefalica da parte del parassita. I dati hanno, quindi, indicato alterazioni significative del sonno e della veglia all’inizio della fase encefalitica della tripanosomiasi africana, con un rialzo dei livelli liquorali di CXCL10 durante l’evoluzione del secondo stadio della malattia.The human body is constantly exposed to the attacks of pathogens which can trigger acute or chronic infections. When this occurs, the general common feeling is a need to sleep. Such somnolence is a component of the so-called sickness syndrome or sickness behavior, which facilitates recovery. However, changes in the sleep-wake pattern may show distinct features during different infections. Marked changes in the sleep-wake pattern, including narcolepsy-like neurophysiological alterations, have been observed following infection with the parasites African trypanosomes. Interestingly, infection with influenza virus has been recently associated with narcolepsy as well. In this doctoral thesis, rodent models of H1N1 influenza A virus infection and African trypanosomiasis were used to investigate the sleep-wake pattern, related neural circuitry and inflammatory mediators. The first investigation (which has been published) was focused on influenza infection. In particular, Rag1-/- mice, which lack adaptive immunity, were used to verify whether a mouse-neuroadapted influenza A virus (A/WSN/33) could cause per se narcoleptic-like changes following intranasal instillation. In the normal sleep structure, rapid eye movement (REM) sleep is preceded by NREM sleep in cyclic sequences. During the fourth we postinfection, a fragmented sleep-wake pattern and alterations of the NREM-REM sleep sequence, with the occurrence of so-called sleep-onset REM (SOREM) episodes, were observed in the murine model of influenza infection. In SOREM episodes, REM sleep is preceded by wake and therefore the NREM-REM sleep sequence is disrupted. Interestingly, immunohistochemistry for A/WSN/33 virus antigens showed in the infected mice hypothalamic and upper brainstem localization, which included subsets of sleep-wake-regulatory neurons. Moreover, upregulation of transcripts encoding pro-inflammatory mediators was seen in the brain of the infected Rag1-/- mice. Our findings thus showed that infection with influenza virus can lead to narcoleptic-like sleep-wake alterations in genetically susceptible subjects. Since the distribution in the brain of influenza virus after intranasal instillation seemed to reflect retrograde axonal transport from the olfactory bulb, the second experiment was focused on the verification of this monosynaptic connection. Unilateral injection of the fluorescent tracer Fluoro-Gold into the olfactory bulb in mice showed that neuronal cell bodies containing orexin/hypocretin, which are located in the lateral hypothalamus, were retrogradely labelled. The findings thus showed that these peptidergic neurons, which play a key role in wakefulness stability and sleep-wake transitions, project directly the olfactory bulb. The third experimental data set was focused on African trypanosomiasis. Staging of this disease is currently based on criteria that lack sensitivity. Since disease staging is needed for effective treatment of the patients, the study was aimed at the investigation of two potential biomarkers of the disease (sleep-wake alterations and levels of the chemokine CXCL10 in the cerebrospinal fluid) at the time of parasite invasion of the brain parenchyma. Sleep-wake changes characterize African trypanosomiasis in humans and in rodent models. The chemokine CXCL10 was previously found to play a key pathogenetic role in parasite neuroinvasion. Trypanosoma brucei brucei-infected rats were used as animal model. Interestingly, CXCL10 levels showed a steep increase in the serum at the time of parasite neuroinvasion and in the cerebrospinal fluid later during the disease. Neurophysiological long-term recordings indicated a progressive sleep-wake fragmentation and invasion of sleep by wakefulness at the time of parasite neuroinvasion.
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IMPERATORE, Roberta. "Endocannabinoid-controlled modulation of orexinergic neurons in obesity: switch from excitatory to inhibitory wiring". Doctoral thesis, 2012. http://hdl.handle.net/11562/407339.
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Alterazioni acute o croniche dello stato energetico provocano cambiamenti negli equilibri tra trasmissione sinaptica eccitatoria ed inibitoria e nella plasticità sinaptica ad essi associata, favorendo l'adattamento del metabolismo energetico alle nuove esigenze omeostatiche. L'impatto di tali cambiamenti, in particolare durante l'obesità, sul segnale degli endocannabinoidi sui recettori CB1, uno dei principali modulatori della trasmissione sinaptica, e uno dei target per i farmaci anti-obesità, non è ben compreso. Gli endocannabinoidi stimolano l'assunzione di cibo e la loro sintesi e rilascio aumentano dopo deprivazione di cibo, inducendo così l'attivazione dei recettori CB1. In particolare i livelli di endocannabinoidi aumentano nell'ipotalamo e nel sangue durante brevi periodi di digiuno (1, 2) e diminuiscono in seguito a somministrazione di leptina e dopo assunzione di cibo (3, 4). Topi con riduzione dei segnali della leptina (topi db/db che esprimono un recettore difettoso della leptina), con carenza di leptina (ob/ob), e con resistenza alla leptina (resistenza acquisita a causa dell’ obesità indotta da dieta, topi HFD) presentano elevati livelli di endocannabinoidi nell'ipotalamo e nel tessuto adiposo (5). Lavori recenti mostrano che la leptina modula anche la crescita degli assoni e la plasticità sinaptica nell'ipotalamo (6,7). In particolare, la leptina incrementa l’estensione degli assoni nel Nucleo Arcuato durante lo sviluppo perinatale del topo, svolgendo così un ruolo trofico all'interno di quei circuiti che saranno oggetto delle azioni fisiologiche della leptina nella vita adulta (6). La leptina può anche agire sui neuroni sintetizzanti Orexina (OX) dell'ipotalamo laterale, i quali inviano proiezioni diffuse al cervello (8) svolgendo un ruolo integrativo strategico nell'alimentazione. La leptina sopprime l'attività dei neuroni OX, la loro biosintesi o entrambi. Inoltre, un antagonista selettivo del recettore OX1R riduce l’assunzione di cibo e diminuisce l’obesità in topi ob/ob (9), suggerendo che la carenza di leptina, almeno in parte, attiva il patway dell’orexina per aumentare l'assunzione di cibo. D'altra parte, il pretrattamento con dosi sub-efficaci di rimonabant, un antagonista selettivo del CB1, attenua l’azione oressigenica dell’OX (10), mentre dati elettrofisiologici sostengono un ruolo inibitorio dei cannabinoidi sui neuroni orexinergici in condizioni fisiologiche (11). Partendo da queste basi, abbiamo studiato se un rimodellamento del wiring neuronale orexinergico si verifica nell’LH nel corso di una prolungata perturbazione nutrizionale causata da, o risultante in, carenza di segnalazione della leptina, come in topi ob/ob e topi HFD, rispettivamente, ed il suo impatto sulla funzione neuromodulatoria del sistema endocannabinoide, dato che un’ alta plasticità neuronale si verifica in questo circuito per un’ adeguata regolazione del bilancio energetico (12).Acute or chronic alterations in energy status lead to changes in the balance between excitatory and inhibitory synaptic transmission and associated synaptic plasticity, facilitating adaptation of energy metabolism to new homeostatic requirements. The impact of such changes, especially during obesity, on endocannabinoid signalling at CB1 receptors, a master modulator of synaptic transmission and strength, and a target for anti-obesity drugs, is not well understood. Endocannabinoids stimulate food intake and their synthesis and release increase after food-deprivation thus inducing activation of CB1 receptors. In particular, endocannabinoid levels increase in the hypothalamus and blood during short-term fasting (1, 2) and decrease after leptin administration and feeding (3, 4). Impairment of leptin signaling (db/db mice expressing a defective leptin receptor), leptin deficiency (ob/ob), and leptin resistance (acquired resistance due to diet-induced obesity, HFD mice) in mice showed elevated levels of Endocannabinoids in the hypothalamus and in adipose tissue (5). Recent papers show that leptin modulates also the axonal growth and synaptic plasticity within the hypothalamus (6,7). In particular, leptin increases neurite extension in the Arcuate Nucleus during mouse perinatal development, thus playing an early trophic role within those circuits that will be the target of leptin physiological actions in adult life (6). Leptin also may act on the Orexinergic-synthesizing (OX) neurons of the lateral hypothalamus, which send widespread projections to the brain (8) playing a strategic integrative role in the feeding. Leptin suppress the activity of OX neurons, the biosynthesis of OX or both. Moreover, an OX1R-selective antagonist reduced food intake and ameliorated obesity of leptin-deficient ob/ob mice (9), suggesting that leptin deficiency at least partly activates the orexin pathway to increase food intake. On the other hand, pretreatment with subeffective doses of rimonabant, a selective CB1 antagonist, attenuates the orexigenic actions of OX (10), whereas electrophysiological data support the inhibitory role of cannabinoids on orexinergic neurons in physiological conditions (11). Staring from these bases, we investigated if a remodeling of orexinergic neuronal wiring occurs in the LH during a prolonged nutritional perturbation caused by, or resulting in, leptin signalling deficiency, as in ob/ob and HFD mice, respectively, and its impact on neuromodulatory function of the endocannabinoid system, since high neural plasticity occurs in this circuitry for adequate regulation of energy balance (12).
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Becker, Thorsten. "On the synaptic rearrangement in the hypothalamus and the periaqueductal gray in an animal model of obesity". Doctoral thesis, 2015. http://hdl.handle.net/11562/915001.
Texto completoResumen
L'obesità è un problema mondiale, che colpisce la salute delle persone e gravare sistemi sanitari. Dal punto di vista del biologo è una complessa interazione di endocrine e neurali meccanismi sottostanti assunzione di cibo, in particolare, una delle sue forme patologiche porta all'obesità. È interessante notare che i pazienti così come modelli animali affetti da anomalie di visualizzazione comportamento alimentare nocicezione alterato.
Un modello di topo fama per l'obesità è la leptina-carente ob/ob topo, il nostro laboratorio ha dimostrato che l'innervazione prevalentemente eccitatoria dei neuroni esprimono orexin (OX-N) nell'ipotalamo laterale (LH) di topi WT è riorganizzato in favore di gli ingressi inibitori di LH di topi ob/ob. Inoltre, il rilascio delle vescicole dagli ingressi inibitori è soppressa via recettore dei cannabinoidi di tipo 1 (CB1) attivazione. Su depolarizzazione un neurone oressinergico sintetizza e "rilascia" endocannabinoidi (eCBs), molto probabilmente 2-AG, che viaggia retrograda al terminale presinaptico e attiva i recettori CB1 presinaptici, sopprimendo così il rilascio delle vescicole da questi terminali (un meccanismo chiamato: depolarizzazione-indotta soppressione di inibizione o DSI). Qui, ho dimostrato che l'innervazione eccitatoria funzionale di OX-N non differiva tra ob/ob e topi WT. Inoltre, l'attivazione dei recettori CB1 presinaptici soppresso il rilascio delle vescicole da ingressi eccitatori, sia wt e topi ob/ob, nella stessa misura. Lo squilibrio di eccitatori funzionale e ingressi inibitori in ob/ob recettori CB1 presinaptici topi, putativamente, lascia OX-N con una membrana iperpolarizzato potenziale e un'attività di cottura ridotta, su depolarizzazione, tuttavia, eCBs sarebbe sintetizzato e rilasciato, viaggi in e attivare , che si trova principalmente su fattori inibitori, sopprimendo il rilascio delle vescicole e disinibendo quindi OX-N. Neuroni oressinergico possiedono vaste proiezioni in tutto il cervello, i.a. per il sistema della dopamina mesoaccumbal e (HPA) ipotalamo-ipofisi-surrene. L'attivazione di queste due circuiti, putativamente, provoca l'aumentata assunzione di cibo visto in ob/ob mouse.
Un'altra area di destinazione di OX-N è il grigio periacqueduttale (PAG), che è noto a svolgere un ruolo chiave nella nocicezione attraverso le vie discendenti antinocicettivi. E 'stato riportato che i pazienti così come modelli animali affetti da comportamento alimentare anormale mostrano anche nocicezione alterata. Inoltre, la somministrazione di orexina A (OX-A) è stata dimostrata per sopprimere le correnti postsinaptiche inibitorie in recettori CB1 modo attivazione mediata, eventualmente, causando una depolarizzazione del potenziale di membrana dei neuroni PAG e, infine, un aumento di cottura attività. Curiosamente, queste osservazioni in vitro si traducono in un comportamento, OX-Un'amministrazione nel PAG elevato la soglia del dolore nei ratti durante il test della coda-flick. ob/ob topo mostravano un elevato livello di OX-A in PAG, simile alla situazione dopo OX-A amministrazione, quindi, abbiamo ipotizzato che i neuroni PAG proiettando al midollo rostroventral (prossimo passo gerarchica dopo PAG nelle vie discendenti antinocicettivi) erano più depolarizzato e hanno un'attività di cottura superiore in topi ob/ob rispetto al peso. Infatti, bloccando il recettore orexina 1 iperpolarizzato il potenziale di membrana e riduce l'attività dei neuroni ob/ob PAG, ma non i neuroni wt PAG. Inoltre, PAG neuroni di topi ob/ob visualizzati potenziale potenziale soglia azione iperpolarizzato rispetto ai topi WT, il che significa che i neuroni ob/ob PAG sono più propensi ad avviare un potenziale d'azione di neuroni WT PAG. Così, suggerendo che l'attivazione dei neuroni PAG dal attivati ingressi oressinergico risultati in una soglia del dolore elevata ulteriormente attivando le vie discendenti antinocicettivi.
In conclusione, l'interruttore di innervazione su OX-N a favore di ingressi inibitori, causato dall'assenza di leptina nel ob/ob topo, attiva OX-N inibendo loro ingressi principalmente inibitori dall'attivazione del recettore CB1 BCE-mediata, conseguente la soppressione del rilascio di vescicole (DSI). Questi disinibito OX-N attivare aree di destinazione in tutto il cervello, come il sistema della dopamina mesoaccumbal e asse HPA, modulando in tal modo il comportamento alimentare. Inoltre, le proiezioni oressinergico a PAG depolarizza il potenziale di membrana e aumenta l'attività dei neuroni PAG proiettano al midollo rostroventral, aumentando così la soglia del dolore.Obesity is a worldwide problem, affecting peoples‘ health and burdening healthcare systems. It is a complex interaction of endocrine and neural mechanisms underlying food intake, in particular, one of its pathological forms leading to obesity. Interestingly, patients as well as animal models suffering from abnormal feeding behavior display altered nociception. A renown mouse model for obesity is the leptin-deficient ob/ob mouse, our laboratory has demonstrated that the mainly excitatory innervation of orexin-expressing neurons (OX-N) in the lateral hypothalamus (LH) of wt mice is rearranged in favor of the inhibitory inputs in LH of ob/ob mice. Furthermore, the vesicle release from the inhibitory inputs is suppressed by endocannabinoids (eCBs) activating cannabinoid receptor type 1 (CB1) activation. The eCBs, most likely 2-AG, originate from the postsynaptic terminals, where they are being synthesized and “released“ as a reaction to depolarization (a mechanism called: depolarization-induced suppression of inhibition or DSI). Here, I demonstrated that the functional excitatory innervation of OX-N did not differ between ob/ob and wt mice. Furthermore, the activation of presynaptic CB1 receptors suppressed the vesicle release from excitatory inputs, in both wt and ob/ob mice, to the same extent. The imbalance of functional excitatory and inhibitory inputs in ob/ob mice, putatively, leaves OX-N with a hyperpolarized membrane potential and a reduced firing activity. Activation of CB1 receptors, mainly located on inhibitory inputs, eventually activate OX-N by disinhibiting them. Orexinergic neurons possess vast projections throughout the brain, i.a. to the mesoaccumbal dopamine system and the hypothalamus-pituitary-adrenal (HPA) axis. The activation of these two circuits, putatively, results in the increased food intake seen in the ob/ob mouse. Another target area of OX-N is the periaqueductal gray (PAG), playing a key role in nociception via the descending antinociceptive pathways. It has been reported that patients as well as animal models suffering from abnormal feeding behavior also display altered nociception. Furthermore, the administration of orexin A (OX-A) has been demonstrated to suppress inhibitory postsynaptic currents in CB1 receptor activation-mediated way, eventually, resulting in a depolarization of the membrane potential of PAG neurons and, finally, in an increase of firing activity. Intriguingly, these in vitro observations translate to behavior, OX-A administration into PAG elevated the pain threshold in rats during the tail-flick test. ob/ob mice displayed an elevated level of OX-A in PAG, similar to the situation after OX-A administration, hence, we hypothesized that the PAG neurons projecting to the rostroventral medulla were more depolarized and have a higher firing activity in ob/ob mice compared to wt. Indeed, blocking the orexin 1 receptor hyperpolarized the membrane potential and reduced the firing activity of ob/ob PAG neurons, but not wt PAG neurons. Furthermore, ob/ob PAG neurons were more likely to initiate an action potential than wt PAG neurons. Thus, suggesting that the activation of PAG neurons by activated orexinergic inputs results in an elevated pain threshold by further activating the descending antinociceptive pathways. In conclusion, the switch of innervation onto OX-N in favor of inhibitory inputs, caused by the absence of leptin in the ob/ob mouse, activates OX-N by inhibiting their mainly inhibitory inputs by eCB-mediated CB1 receptor activation, resulting in the suppression of vesicle release (DSI). These disinhibited OX-N activate target areas throughout the brain, such as the mesoaccumbal dopamine system and HPA axis, thereby modulating feeding behavior. Furthermore, orexinergic projections to PAG depolarizes the membrane potential and increases the firing activity of PAG neurons projecting to the rostroventral medulla, thereby raising the pain threshold.
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Azeez, Idris Ayodeji. "The Oscillating Lateral Hypothalamus and the Orexinergic System". Doctoral thesis, 2018. http://hdl.handle.net/11562/978588.
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Neurons which release the orexins (OX)/hypocretins peptides and are located in the lateral hypothalamus (LH) are key regulators of energy metabolism, arousal and sleep-wake stability, motivated behaviors. This thesis presents three data sets focused on the synaptic wiring of OX-A cell bodies in relation to state-dependent behavior in mice. The first study (Chapter 2; Laperchia et al. 2017) tested the hypothesis of synaptic plasticity phenomena of OX soma innervation in basal conditions. Adult mice were sacrificed during day or night periods in which sleep or wake predominance, respectively, were assessed by electroencephalography in matched mice. Excitatory and inhibitory terminals on OX somata were evaluated with multiple immunofluorescence. The total number of these terminals did not vary between day and night, but glutamatergic terminals prevailed at night and GABAergic ones at daytime. The findings thus revealed a striking daily fluctuation in the axosomatic wiring of OX neurons, with a switch from prevalent excitatory innervation during wake to prevalent inhibitory innervation during sleep. An addendum to Chapter 2 presents methodological approaches to the analysis of astrocytes surrounding OX neurons, at day and night time points in antiphase as above, and preliminary observations. The second study (Chapter 3) tested the hypotheses that the above diurnal fluctuation could be altered during aging and in the pathology that characterizes Alzheimer's disease (AD). The same paradigm and approaches of the first study were applied to 3 month-old and 20 month-old TASTPM mice, which provide a model of AD and in which main pathological features were investigated, and to matched wild-type (WT) mice. The day/night fluctuation in the inhibitory/excitatory wiring of OX somata was replicated in young WT and TASTPM mice, but was lost in aged WT mice and TASTPM mice. In addition, an overall decrease of presynaptic terminals on OX cell bodies was found in aged WT and TASTPM mice vs young ones, and in TASTPM mice vs WT ones (all sampled during daytime). In 15 month-old TASTPM mice stereological OX cell counts revealed significant loss (34% decrease), and densitometric evaluation showed a significant enhancement OX immunosignal intensity, suggesting a potential compensatory increase of peptide synthesis. The third study (Chapter 4) tested the hypothesis that extracellular matrix (ECM) components, reported to be among the players regulating neural plasticity, could be involved in the daily reorganization of OX cell body wiring. The study was conducted in healthy mice and in a murine model of the parasitic encephalitis African trypanosomiasis or sleeping sickness. The ECM was labelled by Wisteria floribunda agglutinin (WFA) immunofluorescence. Marked day/night variations were observed in confocal microscopy, with a diffuse ECM distribution at daytime, and a more compact organization and condensation around OX cell bodies at night. Furthermore, WFA expression in the LH, evaluated with Western blotting, was significantly enhanced at night compared to day. This diurnal variation of ECM organization was not found in other brain areas (suprachiasmatic nucleus, neocortex, hippocampus), and was lost in the LH after African trypanosome infection. These findings indicate regional day/night fluctuation of the ECM in the LH, and its disruption in a chronic neuroinflammatory pathology which leads to sleep-wake dysregulation.
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Hirvonen, Matt David. "Regulatory adjustments in body protein following lesions of the lateral hypothalmus". 1994. http://catalog.hathitrust.org/api/volumes/oclc/32600656.html.
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Thesis (Ph. D.)--University of Wisconsin--Madison, 1994.Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 89-92).
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Mitchell, Caitlin. "Characterising how chronic stress and natural rewards impact lateral hypothalamic circuitry". Thesis, 2020. http://hdl.handle.net/1959.13/1417341.
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Research Doctorate - Doctor of Philosophy (PhD)The lateral hypothalamus (LH) is anatomically positioned to receive and send an array of afferent and efferent signals within the brain. This is important as distinct behaviours relating to homeostasis are coordinated and executed by LH cells and signalling pathways. The LH can control appetitive behaviour as well as motivation and reward-seeking, as well as being sensitive to stress signals. Importantly, the LH has a heterogenous composition, comprising of many diverse cell types. The functional importance of these intra-LH populations is incompletely understood. Further, neuroscience research is only recently beginning to unravel the complex nature of afferent signals which can help control output from the LH. Afferent projections from brains areas such as the paraventricular nucleus of the hypothalamus (PVN) and nucleus accumbens shell (NAcSh) can control stress and reward-related behaviour, respectively. These regions are well positioned anatomically and physiologically to send important communications to the LH in order to help maintain homeostatic functioning. This thesis firstly demonstrated that early life stress-induced motivational deficits have the capacity to be overcome by chemogenetic manipulation of the LH. Next, we saw that repeated optogenetic stimulation of the PVN can reduce motivational drive for natural rewards. Importantly, these changes could be recapitulated by isolating the PVN→LH pathway. Lastly, using fibre photometry we found that orexin neurons almost exclusively respond to approach behaviour to food pellets and that the activity of orexin neurons depended on metabolic state and the palatability or caloric value of the food. Additionally, we provide electrophysiological evidence that this behaviour may be mediated by an inhibitory projection from the NAcSh. Overall, this work demonstrates that hypothalamic and extra-hypothalamic brain regions can provide vital input to the LH in mediating stress and motivated behaviours.
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Yeoh, Jiann Wei. "Drug-induced changes to lateral hypothalamic circuits and downstream projection targets". Thesis, 2015. http://hdl.handle.net/1959.13/1309854.
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Research Doctorate - Doctor of Philosophy (PhD)The lateral hypothalamus (LH) contains a large number of neuropeptide transmitter-expressing neurons that act to co-ordinate consummatory and reward-seeking behaviours. My thesis focuses on two classes of these neuropeptides; orexins, of which I generally classified as ‘pro’ reward-seeking and cocaine and amphetamine reward transcript (CART) peptides, commonly considered to be ‘anti’ reward-seeking. For example, in the context of drug addiction, activation of the orexin system generally promotes the reinstatement of cocaine-seeking behaviour, whereas the majority of the studies have demonstrated that increased CART signalling negatively regulates drug-motivated behaviours. Critically, it remains unclear how these systems interact and modulate the output of key nodes of the reward seeking circuitry. Therefore, in this thesis I address a number of outstanding questions regarding how changes in the activity of orexin or CART neurons might behavioural output controlled by the reward-seeking circuit. First, using ex vivo slice electrophysiology, I assessed how orexin circuitry in the LH is modified by cocaine exposure in rats that were passively exposed to cocaine or were trained to self-administer cocaine in operant boxes. Immunohistochemical detection of markers of glutamatergic versus GABAergic synapses was used to estimate and identify changes in presynaptic inputs onto orexin neurons after cocaine. I found evidence of increased presynaptic drive and excitatory terminals onto orexin neurons irrespective of whether animals self-administered or injected passively with cocaine. In Chapter 2, I determined if similar changes occur in orexin neurons from transgenic mice where the reporter gene (green fluorescent protein, GFP) was driven by the orexin promoter. These studies are important in order to take advantage of the expanding transgenic approaches in mice in the future. Further, I also tested the longevity of presynaptic drive to orexin neurons produced by cocaine and examined whether activation of group III metabotropic glutamate receptors could reverse any of the changes induced by cocaine. These studies showed that presynaptic drive to LH orexin neurons persists for at least two weeks after animals were withdrawn from cocaine. Further, activation of GP-III mGluRs curtailed the cocaine-induced increase in glutamate release onto orexin neurons. Previous work in our lab has identified that CART peptide injections but not orexin receptor antagonism in the PVT negatively regulates drug seeking behaviour. Therefore I assessed in Chapter 3 how cocaine influences the normal firing properties of PVT neurons and whether, as predicted by our previous behavioural studies, CART reduces PVT neuron activity. In the final chapter of my thesis, I summarise and integrate my results in the context of the wider literature and attempt to present a synthesis of LH based changes with relevance to addiction and other psychiatric conditions such as depression and anxiety.
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Georgescu, Dan. "The role of lateral hypothalamic neuropeptides in drug addiction and feeding behavior". 2004. http://edissertations.library.swmed.edu/pdf/GeorgescuD081904/GeorgescuDan.pdf.
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West, Thomas Edward George. "Effects of naltrexone on nucleus accumbens, lateral hypothalamic and venetral tegmental brain stimulation reward". Thesis, 1986. http://spectrum.library.concordia.ca/5790/1/ML35578.pdf.
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Flores, Cecilia. "Fos-like immunoreactivity in forebrain regions following self-stimulation of the lateral hypothalamus and ventral tegmental area". Thesis, 1995. http://spectrum.library.concordia.ca/3304/1/MM10848.pdf.
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This research aims to visualize neurons activated by both the lateral hypothalamus and ventral tegmental area in order to delimit the search for the first-stage substrate responsible for the rewarding effects of medial forebrain bundle stimulation.--Cf. leaf 78.