Дисертації з теми "Plasticità neuronale"
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Alessandri, Marco <1976>. "Messa a punto di metodi per lo studio della plasticità neuronale del sistema nervoso enterico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2008. http://amsdottorato.unibo.it/822/1/Tesi_Alessandri_Marco.pdf.
Повний текст джерелаAlessandri, Marco <1976>. "Messa a punto di metodi per lo studio della plasticità neuronale del sistema nervoso enterico." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2008. http://amsdottorato.unibo.it/822/.
Повний текст джерелаLEONE, LUCIA. "Ruolo del complesso distrofina-distroglicano e delle metalloproteasi nella plasticità neuronale e sinaptica del ganglio cervicale superiore di roditori." Doctoral thesis, La Sapienza, 2005. http://hdl.handle.net/11573/916857.
Повний текст джерелаOLLA, PIERLUIGI. "Effetti dell'isolamento sociale sull'assunzione di etanolo e sulla plasticità neuronale del recettore GABA_a nell'ippocampo di topi C57BL/6J." Doctoral thesis, Università degli Studi di Cagliari, 2011. http://hdl.handle.net/11584/266278.
Повний текст джерелаCAROSI, CHIARA. "Regolazione dell'espressione genica dell'mRNA di FMR1, responsabile della sindrome dell'X fragile: implicazioni nel ritardo mentale e nella plasticità sinaptica." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2008. http://hdl.handle.net/2108/427.
Повний текст джерелаThe 5’ and 3’ untranslated regions (UTRs) play important roles in regulating gene activity. Within the promoter of the human FMR1 gene, responsible for the Fragile X syndrome, there are multiple transcription start sites in both lymphoblastoid and neuronal cell lines, a common feature of other promoters that lack the TATA box initiator element. In this study I have identified a fourth transcription initiation site in human brain tissue, including hippocampus and cerebellum. All four sites co-localize with an initiator (Inr)-like sequence, commonly found at transcriptional start sites within TATA-less promoters. No detectable activity of the fourth site was observed in lymphoblastoid lines, suggesting a tissue-specific determinants of start site selection. Preliminary data indicate that the longer transcripts (upstream Inrs) are expressed at higher levels with increasing CGG repeat number, providing further support for an initiation model in which the CGG repeat element in the FMR1 gene directly modulates upstream initiation, and in a tissue-specific manner. I have also analyzed the presence of alternative transcription start sites in the promoter of mouse FMR1 gene. I compared the wild type mouse with the transgenic mouse CGG ki, that including in the 5’UTR of FMR1 100 CGG repeats of human gene. In mouse analysis I find several multiple initation sites but I did not find any differences in their usage between wild-type and the CGG ki mice. I have also studied alternative polyadenylation usage in the 3’UTR of the human FMR1 gene, since, the presence of alternative polyadenylation sites has been associated with tissue specific localization of other mRNA species. Using 3’RACE methodology, I have identified five polyadenylation sites, one canonical and four non canonical. These preliminary analysis indicates that transcripts containing the different polyadenylation sites are expressed in both human cell lines and human brain tissues. In this study I also investigated the role of UTRs in antidepressants treatment. Antidepressants are the third most commonly sold group of therapeutic agents worldwide. Most of them are based on molecules, such as fluoxetine, that target a single protein in the brain, the serotonin (5-HT) transporter. Effects of depression are probably localized at both pre- and postsynaptic compartments suggesting that changes in synaptic structure are related to the impaired modification in synaptic strength observed in patients with depression. Based on these hypothesis/observations, key target molecules of the antidepressant treatment are receptors, kinases, neurotrophic factors and protein involved in neurogenesis as well as synaptic function such as αCaMKII. I used the 3’RACE to determine if acute treatment of neurons with fluoxetine would change the αCaMKII mRNA expression in mouse neuronal cortical culture. I obtained that fluoxetine treatment induces a shift in the alternative polyadenylation site usage of αCaMKII mRNA as well as an increase in the total αCaMKII protein in cortical primary culture. These results show that the dendritically localized αCaMKII mRNA changes its pattern of expression after antidepressant treatment. They also show that this treatment affects the use of alternative polydenylation allowing neurons to achieve different levels of protein, possibly translating αCaMKII with a higher efficiency. Key Words: 5’ UTR, 3’ UTR, transcription start site, polyadenylation, dendritic mRNAs, neuronal gene expression, synaptic plasticity, fluoxetine.
Ménardy, Fabien. "Reconnaissance des signaux de communication chez le diamant mandarin : étude des réponses des neurones d’une aire auditive secondaire." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T049/document.
Повний текст джерелаHow sensory signals are encoded in the brain and whether their behavioural relevance affects their encoding are central questions in sensory neuroscience. Studies have consistently shown that behavioural relevance can change the neural representation of sounds in the auditory system, but what occurs in the context of natural acoustic communication where significance could be acquired through social interaction remains to be explored. The zebra finch, a highly social songbird species that forms lifelong pair bonds and uses a vocalization, the distance call, to identify its mate offers an opportunity to address this issue. One auditory area in the songbird telencephalon, the caudo-medial nidopallium (NCM) that is considered as being analogous to the secondary mammalian auditory cortex, has recently emerged as part of the neural substrate for sensory representation of species-specific vocalizations: the activation of NCM neurons is greatest when birds are exposed to conspecific song, as compared to heterospecific song or artificial stimuli. This led us to investigate whether, in the zebra finch, NCM neurons could contribute to the discrimination among vocalizations that differ in their degree of familiarity: calls produced by the mate, by familiar individuals (males or females), or by unfamiliar individuals (males or females). In females, behaviourally relevant calls, i.e. the mate’s call and familiar calls, evoked responses of greater magnitude than unfamiliar calls. This distinction between responses was seen both in multiunit recordings from awake freely moving mated females (using a telemetric system) and in single unit recordings from anesthetized mated females. In contrast, control females that had not heard them previously displayed response of similar magnitude to call stimuli. In addition, more cells showed highly selective responses in mated than in control females suggesting that experience-dependent plasticity in call-evoked responses resulted in enhanced discrimination of auditory stimuli. In males, as in females, call playback evoked robust auditory responses. However, neurons in males did not appear capable of categorizing the calls of individuals (males or females) as ‘‘familiar’’ or ‘‘unfamiliar’’. Then, we investigated how calls are represented in the NCM of zebra finches by assessing whether certain call-specific acoustic cues drove NCM neurons to a greater degree than others. Behavioural studies had previously identified call-specific acoustic cues that are necessary to elicit a vocal response from male and female zebra finches. Single-unit recordings indicated that NCM neurons in females were particularly sensitive to call modifications in the spectral domain: suppressing the fundamental frequency of call stimuli or modifying the relative energy levels of harmonics in call caused a marked decrease in response magnitude of NCM neurons. In males, NCM neurons also appear to be sensitive to call modifications in the spectral domain, however changes in magnitude of responses (increase or decrease) depended on the acoustic cue that had been modified.Our results provide evidence that the NCM is a telencephalic auditory region that contributes to the processing of the distance call, in females as well in males. However, how the distance call is processed and represented in the NCM appears to differ between males and females. In females, the NCM could be involved in dicrimination between call stimuli whereas, in males, its functional role in call-processing remains to be determined. Our results also suggest that, in females, social experience with the call of individuals, by affecting the degree to which neurons discriminated between these calls, may shape the functional properties of neurons in a telencephalic auditory area. The functional properties of auditory neurons may therefore change continuously to adapt to the social environment
Hilal, Muna. "Role of Scribble1 in hippocampal synaptic maturation, bidirectional plasticity and spatial memory formation in mice." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22037/document.
Повний текст джерелаSpatial memory formation is a complex process that transforms newly-acquired information into long-lasting and solid memories. Molecularly, these phenomena rely on the expression of two opposite forms of synaptic plasticity; long-term potentiation (LTP) and long-term depression (LTD). LTP/LTD induction relies on a fine balance between Ca2+-sensitive kinases and phosphatases that activate specific pathways of either LTP or LTD, respectively. This regulation also involves downstream interactions between receptors and highly specialized scaffold proteins, at the PSD. Scribble1 (Scrib1) is a scaffold protein that belongs to the LAP (leucine-rich repeats and PDZ domains) protein family, with 16 leucine rich repeats and 4 PDZ (PSD-95/Dlg/ZO-1) domains. Here, we developed conditional knock-out mice with a complete loss of Scrib1 expression in the major neurons of the postnatal forebrain, including hippocampal excitatory neurons, using the Cre-Lox system (Scrib1f/f,CaMKII-cre). Scrib1f/f,CaMKII-cre presented altered morphology of apical dendrites but intact spine density and spine morphology in the CA1 region. Functionally, we found increased number of silent (non-functional) synapses that decreases the number of active synapses in Scrib1f/f,CaMKII-cre CA1 neurons leading to a global decrease in basal glutamatergic synaptic transmission at CA3-CA1 synapses compared to Scrib1f/f synapses. Scrib1f/f,CaMKII-cre synapses displayed enhanced LTP but were unable to express LTD or long-term depotentiation. More strikingly, LTD-inducing protocols generated LTP in Scrib1f/f,CaMKII-cre synapses. Molecularly, we revealed a direct interaction between Scrib1 and the phosphatase PP2A that signals LTD at the synapse. Moreover, we found that the absence of Scrib1 results in a reduction of synaptic PP2A levels in Scrib1f/f,CaMKII-cre mice. This probably leads to a decrease in PP2A signaling pathway activation which favors the competing pathway downstream CaMKII resulting in LTP induction instead of LTD in Scrib1f/f,CaMKII-cre mice. On the cognitive level, we found that spatial learning was slower and inflexible in Scrib1f/f,CaMKII-cre compared to Scrib1f/f mice. Short-term spatial memory was intact while long-term memory was impaired. These results argue for an important role of Scrib1 in spatial memory consolidation. We here report that Scrib1 is important for appropriate neuronal shaping and wiring of CA1 neurons as well as functional conversion of silent synapses into active ones. Importantly, it allows bidirectional synaptic plasticity through interaction with PP2A and modulates long-term spatial memory formation
Higgins, David Conal. "A theoretical and numerical study of certain dynamical of synaptic plasticity." Paris, Ecole normale supérieure, 2014. http://www.theses.fr/2014ENSURI01.
Повний текст джерелаSynaptic efficacy measures the ability of a presynaptic neuron to influence the membrane potential of a postsynaptic neuron. The process of changing synaptic efficacy, via plasticity, is thought to underlie learning and memory in the brain. Focusing on chemical synapses, we examine tho abstract rules of synaptic plasticity which determine how changes in synaptic efficacy occur. Beginning with an atypical, non-Hobbian synapse, the parallel fibre to Purkinje cell synapse, we develop a model which explains the burst frequency and length dependence of this particular synaptic plasticity rule. We present a model based on underlying calcium and NO pathways which accurately unifies much of the experimental literature. This model will be useful in future studios of synaptic plasticity for this synapse and its simplicity will allow for numerical studios involving large numbers of synapses in a network architecture. We also examine a more typical plasticity rule for neocortical synaptic plasticity, developing analytical tools which accurately predict the behaviour of this synapse model under pre- and postsynaptic Poisson spiking. Building on this analysis we extend the theory to leaky integrate-and-fire (LIF) neurons in a network. We develop theoretical tools which can accurately describe the network response to both constant and transiently elevated noisy external inputs. Utilising those tools we examine the duration of synaptic memories under ongoing background (1/sec) spiking activity both in independent neurons and in a recurrent network. We find that lowering tho extracellular calcium concentration extends memory time scales and that the further introduction of a bistability to tho synaptic plasticity rule extends this memory time scale by several orders of magnitude. In al! cases we providc theoretical predictions of memory time scales which match subsequent simulation comparisons. Both sets of investigations reveal insights into the processes of learning and subsequent forgetting in the brain. Both models reveal the joint importance of burst frequency and relative spike timing in the induction of memory changes at the synaptic level. Adjustment of model parameters to more closely mimic in vivo conditions extends the retention time of memories, under ongoing activity, to biologically relevant time scales. Our work represents a coherent development right through from the biophysical processes of synaptic plasticity to the analytical mean-field level
Daouzli, Adel Mohamed Renaud Sylvie Saïghi Sylvain. "Systèmes neuromorphiques étude et implantation de fonctions d'apprentissage et de plasticité /." S. l. : Bordeaux 1, 2009. http://ori-oai.u-bordeaux1.fr/pdf/2009/DAOUZLI_ADEL_MOHAMED_2009.pdf.
Повний текст джерелаSoula, Anaïs. "Rôle des microARNs cellulaires et vésiculaires dans la régulation transcriptomique du système nerveux." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0794/document.
Повний текст джерелаThis work consists in stuying the expression, the role and the transport of microRNAs (miRNAs) in the central nervous system (CNS). microRNAs (miRNAs) are small endogenous non coding RNAs, exerting a negative regulation on gene expression.They inhibit protein translation by hybridization on the 3’ untranslated region of mRNA.First, we have revealed the specific role of miR-92a in the control of the expressionof GluA1, in an homeostatic plasticity paradigm in which the synaptic plasticity is inhibited.Second, by using RNA-Seq technology, we showed that miRNAs are differentially expressed in the different structures of the CNS. Moreover, we have discovered new species of miRNAs. Finally, our results suggest that the miRNA expression (of known and new miRNAs) participate in the singular transcriptomique signature of each structure.Third, we have shown that miRNAs are transported into EVs, and can be exchanged between the cells of the CNS. The miRNA content of EVs varies depending on neuronal activity. Target prediction of these miRNAs includes genes involved in the regulation of neuronal plasticity. Together, our results suggest that the exchange of miRNAs through EVs is a new mechanism involved in the modulation of neuronal plasticity. Finally, we propose a new tool for purifiying EVs depending on their cellular origin.To conclude, this study allows a better understanding of the role of miRNAs in the regulation of the physiology of the CNS
Tonelli, Paul. "Relations entre plasticité synaptique et régularité des codages en neuro-évolution." Paris 6, 2012. http://www.theses.fr/2012PA066295.
Повний текст джерелаThe evolution of artificial neural networks or neuro-evolution is able to generate networks capable of solving non-trivial tasks such as makin polyarticulated robots walk or enabling mobile robots to navigate autonomously. However, in most cases, the evolved controller may only solve the problemswhich have already been encountered during the evolutionary process, and the controller cannot adapt online to cope with new situations. Our work establishes the link between two domains of neuro-evolution previously studied independently. On the one hand, synaptic plasticity mechanisms, used as building block in these algorithms to create networks that adapt online and on the other hand, the generative encodings promoting regularity in the createdneural networks. The first contribution of our work is to show that the combination of these two tools provides the ability to generate networks that can adapt online to unknown situations, while the majority of other methods can not: the networks are often only able to "switch" between cases presented during evolution (a phenomenon that can be compared to overlearning) or can only be robust to changes in the environment without any qualitative change in their behavior. Generative encodings promoting regularity, on the contrary, where the same structures are applied to a set of neurons, make it more difficult for the algorithm to overspecialize the evolved networks. Our second contribution solves another problem encountered when evolving neuralnetworks using generative encodings promoting regularity: these encodings generate networks where the behavior of "bundled" neurons is similar, which does not allow them to single out the behavior of any neuron. The addition of synaptic plasticity mechanisms relaxes this constraint by allowing the network to learnin a set of behaviors from a common rule, even if these behaviors are different from one another
Coget, Arthur. "Etude et modélisation de la plasticité cérébrale chez des patients porteurs de lésions gliales de bas grade opérés en chirurgie éveillée." Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTS053.
Повний текст джерелаIntroductionDiffuse low-grade gliomas (DLGG) are slow-growing brain tumors occurring in young adults. This slow progression induces extensive neuroplasticity and explains why patients most of the time do not show any obvious neurological deficit at the time of diagnosis although tumors are located in ‘eloquent’ areas. Therefore DLGG provide an interesting model in understanding mechanisms of neuroplasticity.Awake surgery with direct cortical and subcortical electrostimulation mapping is recommended as first-line treatment of DLGG, allowing to maximize tumoral resection and limiting postoperative neurological deficit, maintaining patients quality of life.Resting-state fMRI, based on BOLD signal analysis, is used to study functional connectivity and neural plasticity. This technique allows robust evaluation of neural networks without performing a task. Consequently, it bypasses the impact of confusion, sedation or neurological deficits on task execution. In this thesis, we aimed to investigate perioperative functional connectivity modifications in order to evaluate neural plasticity after awake surgery.Subsequently we explained the functional results using multimodal MRI imaging to analyze anatomic connectivity and hemodynamic parameters.Methods82 patients with DLGG who underwent awake surgical resection were included in the principal study. MRI acquisitions were performed successively before, within 36 h after and three months post-surgery. All scans were executed on the same MRI magnet for each patient, i.e. either a 3.0 T magnet (Skyra, Siemens) or a 1.5 T magnet (Avanto, Siemens). First, data were preprossed using a standardized classical pipeline and analyzed with the CONN toolbox v16.a.Second, anatomic connectivity was evaluated using diffusion tensor imaging of the corpus callosum.Finally hemodynamic changes induced by surgery were assessed with traditional perfusion imaging as well as using an innovative analysis of the BOLD signal’ s temporal shift.ResultsSurprisingly, it was found that specifically a diffuse transient postoperative interhemispheric disconnectivity occurred between homologous regions, known as homotopic connectivity.In parallel, immediate and long-term postoperative alterations in the anatomic connectivity of the corpus callosum were observed. Immediate and long-term postoperative modifications were also found regarding both regional and global hemodynamics characteristics. Yet, no significant link between the homotopic connectivity findings and the anatomical and hemodynamic changes could have been established at this point.Nevertheless, the hemodynamic analysis allowed the identification of a a specific brain region : the striatum. It was hypothesized that it acts as a central region for the maintenance of homotopic connectivity, explaining simultaneously the decreased post-surgical homotopic connectivity observed.ConclusionThe highlighted transient postoperative functional homotopy is probably due to multifactorial causes To start entangling these causes, the use of anatomic and hemodynamic imaging data analyses seems crucial to interpret functional connectivity data both immediate and long-term postoperative.Cerebral vasoreactivity and modelling studies provide thereby a very promising tool to better understand the interrelated processes underlying postoperative functional connectivity modifications
Cheval, Hélène. "Rôle de la famille de facteurs de transcription Egr dans la mémoire et la plasticité synaptique." Paris 11, 2009. http://www.theses.fr/2009PA11T003.
Повний текст джерелаMorisset, Valérie. "Plasticité fonctionnelle dans la moelle épinière : caractéristiques et neuromodulation des propriétés membranaires intrinsèques des neurones de la corne dorsale." Bordeaux 2, 1999. http://www.theses.fr/1999BOR28644.
Повний текст джерелаCaptain-Sass, Sylvie. "La plasticité neuronale comme nouveau territoire de l'imaginaire." Thesis, Paris 1, 2015. http://www.theses.fr/2015PA010571/document.
Повний текст джерелаSince the 16th century, the collaboration between artists and scientists has gone along with an evolution of representations of a more and more fragmented body. The neuroplasticity theory, as revolutionary for some people as the one of Copernicus or of Darwin, has made a start on the lines of new scientific, but also philosophical and social paradigms, on which contemporary artists rely in a poetic, sometimes ironic and denunciatory way. From the high value given to science to the recent protocols and concepts manipulation, some artistic techniques also rely on the spectacular and stimulating breakthrough of biotechnologies. The questions linked to distortion, impermanence and interaction come with those of plasticity, being neuronal, physical or in connection with materials. From these context elements, this thesis analyzes the issues linked to the approaches from artists grappling with these plasticities at work. Taking into consideration the mutual influence relationship existing between brain and body plasticity, I also analyze the impact of Shintaido, a Japanese martial art, on my poïesis. The use of wax, a both modest and sacred plastic material, is confronted to the use of raw canvas, dragging out maps with a mysterious syntax from brain and body matter, like telluric nomadic wanderings that have become more ethereal today
Carney, Karen. "Caractérisation Protéomique Des Prolongements Astrocytaires au Cours de la Plasticité Synaptique." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0270/document.
Повний текст джерелаAstrocytes are the most abundant cell type in the brain and mediate a myriad offunctions, including neurogenesis, ion homeostasis, metabolic support, clearance oftoxic substances and responses to brain injuries. Alterations in astrocyte functionhave been linked with neurological disorders such as epilepsy, depression, dementiaand schizophrenia, and thus the continued study of astrocytic contributions tosynaptic function are of clinical and societal relevance. In this thesis I have evaluatedthe potential utility of several preparations for the assessment of astrocyte proteinsinvolved in the regulation of synaptic plasticity, and employed the most suitable ofthese preparations to measure regulation in astrocyte protein levels in models ofsynaptic plasticity. I have characterized several preparations that can be used toevaluate astrocyte contributions to synaptic plasticity and identified numerousastrocyte-enriched proteins regulated by synaptic plasticity that can be targeted infuture studies to elaborate upon the mechanisms of action of astrocytes in bothphysiological and pathological contexts
Ahdab, Rechdi. "Plasticité des représentations corticales motrices après accident vasculaire cérébral." Thesis, Paris Est, 2010. http://www.theses.fr/2010PEST0031.
Повний текст джерелаFollowing stroke, reorganization of the motor cortical maps takes places and involves both the primary motor cortex (M1) and the premotor cortex (PMC) on the affected hemisphere. The relative contribution of each of these two cortical areas in the process of post-stroke plasticity and motor recovery remains uncertain. The present project was designed to study the cortical changes that follow a motor stroke, namely those involving M1 and the PMC, and their implications for motor recovery. For this purpose we used MRI-guided (neuronavigated) transcranial magnetic stimulation (TMS). First, we defined the anatomical limits of the cortical areas and the reliable cortical landmarks within each region of interest. We then defined a normal motor map in a group of healthy subjects. Our “probabilistic” map was based on the probability of obtaining motor responses in a given area and therefore accounted for inter-subject variability of motor representations. Thereafter we studied the modifications of the motor cortical representations in a group of patients having recovered from a motor stroke. Finally, we prospectively followed a group of patients presenting with a motor stroke. By comparing the neurophysiological and clinical data at admission and three months later, we were able to characterize the anatomo-functional cortical changes that accompany motor recovery following stroke. Our results are consistent with a major role of M1 in motor recovery. To conclude, we propose a model of how the motor cortex works in healthy subjects and during post-stroke recovery process
Dufor, Tom. "Low intensity rTMS to the cerebellum : age dependent effects and mechanisms underlying neural circuit plasticity." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066270/document.
Повний текст джерелаNeuroplasticity is essential for the establishment and strengthening of neural circuits during the critical period of development, and are required for the brain to adapt to its environment. The mechanisms of plasticity vary throughout life, are generally more difficult to induce in the adult brain, and decrease with advancing age. Repetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical excitability and shows promise in the treatment of some neurological disorders. Low intensity magnetic stimulation (LI-rTMS), which does not directly elicit action potentials in the stimulated neurons, have also shown some therapeutic effects, and it is important to determine the biological mechanisms underlying the effects of these low intensity magnetic fields, such as would occur in the regions surrounding the central high-intensity focus of rTMS. We have used a focal low-intensity magnetic stimulation (10mT) to address some of these issues in the mouse cerebellum and olivocerebellar path. The cerebellum model is particularly useful as its development, structure, ageing and function are well described which allows us to easily detect eventual modifications. We assessed effects of in vivo or in vitro LI-rTMS on neuronal morphology, behavior, and post-lesion plasticity. We first showed that LI-rTMS treatment in vivo alters dendritic spines and dendritic morphology, in association with improved spatial memory. These effects were age dependent. To optimize stimulation parameters in order to induce post-lesion reinnervation we used our in vitro model of post-lesion repair to systematically investigate the effects of different LI-rTMS stimulation patterns and frequencies. We showed that the pattern of stimulation is critical for allowing repair, rather than the total number of stimulation pulses. Finally, we looked for potential underlying mechanisms participating in the effects of the LI-rTMS, using mouse mutants in vivo or in vitro. We found that the cryptochromes, which have magnetoreceptor properties, must be present for the response to magnetic stimulation to be transduced into biological effects. The ensemble of our results indicate that the effects of LI-rTMS depend upon the presence of magnetoreceptors, the stimulation protocol, and the age of the animal suggesting that future therapeutic strategies must be adapted to the neuronal context in each individual person
Gagnon, Dave. "Plasticité adaptative de la microcircuiterie neuronale des ganglions de la base dans la maladie de Parkinson." Doctoral thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/29907.
Повний текст джерелаThe basal ganglia are a set of subcortical structures involved in psychomotor behaviour. Parkinson’s disease is the most common neurodegenerative disorder affecting the basal ganglia. The slow and progressive degeneration of dopamine (DA) neurons located in the substantia nigra pars compacta leads to disabling motor symptoms such as bradykinesia, resting tremor and rigidity. This work aims at describing the compensatory mechanisms affecting other neuronal systems and designed to compensate for the massive loss of the DA innervation of the basal ganglia. The thesis begins with a post-mortem human study of the main serotonin (5-HT) pathways arising from the raphe nuclei and innervating the different basal ganglia components in normal condition. The next chapter contains a morphological study providing the first detailed description of single axons arising from the dorsal raphe nucleus (DRN) in rats. In order to achieve our goal, under electrophysiological guidance, microiontophoretic tracer injections of an anterograde tracer were placed in the DRN to provide three-dimensional axonal reconstructions of single 5-HT neurons. Other studies presented were performed in animal models of Parkinson’s disease and brought to light new compensatory mechanisms involving the 5-HT and DA innervation of the basal ganglia. Two articles contain data on major neuroadaptative changes of DA and 5-HT innervation of the striatum and the globus pallidus (GP), following a DA lesion in cynomolgus monkeys (Macaca fascicularis). Immunohistochemistry combined to unbiased quantitative approaches indicate an important sprouting of 5-HT axons in the monkey striatum and GP. Interestingly, in contrast to the massive striatal DA denervation, we report a ten-time increase of the number of DA axons in the GP internal segment of parkinsonian monkeys. Electron microscopy study suggests that the newly-formed 5-HT axon varicosities observed in the striatum establish more synapses after DA lesion, in line with the sprouting of 5-HT axons. The last chapter contains a meticulous morphological study of a peculiar population of medium spiny neurons endowed with a dendritic arborization that is less affected by DA lesion in mice. In summary, studies presented in this doctoral thesis shed a new light on some of the compensatory mechanisms observed in different basal ganglia components and designed to cope for the massive loss of DA neurons that characterize Parkinson’s disease. The compensatory mechanisms outlined in this work should be taken into account to better understand the expression of motor and non-motor symptoms as well as the expression of dyskinesia induced by long-term pharmacological treatment with L-Dopa.
Linnarsson, Sten. "Neurotrophic factors and neuronal plasticity /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4618-3/.
Повний текст джерелаMysore, Shreesh Pranesh Schuman Erin Margaret Quartz Steven. "Structural plasticity in neuronal networks /." Diss., Pasadena, Calif. : California Institute of Technology, 2007. http://resolver.caltech.edu/CaltechETD:etd-11102006-021149.
Повний текст джерелаSallagundala, Nagaraja. "Neuronal hypothalamic plasticity in chicken." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15600.
Повний текст джерелаIn the present electrophysiological studies, characterization of neuronal hypothalamic plasticity in the chicken aims to investigate the influence of age during development by extracellular recordings. High neuronal cold sensitivity has been found in juvenile chicken in contrast to adult mammals and birds. High hypothalamic cold sensitivity seems to be a specific characteristic feature in juvenile birds. Between species a species specificity of the early development of neuronal hypothalamic thermosensitivity could be clearly demonstrated. Existence of inherent nature to a certain degree suggests a possible thermoregulatory role of cold-sensitive neurons in chicken. The effects of the GABAergic substances on neuronal tonic activity (firing rate) and temperature sensitivity (temperature coefficient) in hypothalamic neurons have been examined. Muscimol and baclofen in equimolar concentrations significantly inhibited tonic activity, regardless of their type of thermosensitivity. In contrast bicuculline and CGP 35348 increased firing rate. Temperature coefficient was significantly changed by ligands of GABAB receptors, restricted to cold-sensitive neurons. The TC was significantly increased by baclofen and significantly decreased by CGP 35348. Effects of muscimol and baclofen on firing rate and TC were prevented by co-perfusion of appropriate antagonists bicuculline and CGP 35348, respectively in tenfold higher concentration. Thus the main effects of GABA in chicken are similar with that described in mammals. The only difference is in respect of the GABAB receptors mediated change restricted to cold-sensitive neurons in chicken but in mammals only seen in warm-sensitive neurons. However, the results indicate that the fundamental mechanism of GABAergic influence in chicken are conserved during evolution. The response of hypothalamic neurons to temperature changes suggest a possible functional role of GABAergic substances in the control of body temperature in birds.
Forest, Jérémy. "Impact of adult neurogenesis versus preexisting neurons on olfactory perception in complex or changing olfactory environment." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1326/document.
Повний текст джерелаOlfaction is a key player in behavioral adaptation. To perform tasks accurately, the olfactory system has to perform fine discrimination between very close stimuli. The discrimination performances can be enhanced through perceptual learning and a key cerebral structure in this is the olfactory bulb. This structure is the target of a specific form of plasticity that is adult neurogenesis. In this structure, adult-born neurons differentiate mostly in granule cells that regulate the activity of the relay cells. It has previously been shown that these neurons are required to perform perceptual learning. The central question of this thesis work is to elucidate both the role and the specificity of adult born neurons during complex or changing olfactory learning.We first studied the effect of complex perceptual learning on adult neurogenesis. This study demonstrated the necessity and sufficiency of adult-born neurons for simple olfactory learning. It also showed that when learning becomes complex, a larger neural network is involved requiring preexisting neurons.The olfactory environment is also changing. In a second study we investigated how the memory of an olfactory information is altered by the acquisition of a new one and what is the role of adult neurogenesis in this process. This second study highlighted the role of adult-born neurons in underlying olfactory memory and the importance of delay between learning for memory stabilization.Lastly, an approach relying on computational neurosciences aimed at outlining a computational framework explaining the role of adult-born granule cells in early olfactory transformations and how sharpened sensory representations emerge from decorrelation.To conclude, olfactory perception is changing according to environmental modifications and this plasticity is underlain by an important plasticity of the olfactory bulb circuitry due in large part to adult neurogenesis
Bellier, Ludovic. "Encodage neuronal des sons de parole : développements méthodologiques, générateurs neuronaux et application au malentendant appareillé." Thesis, Lyon 1, 2015. http://www.theses.fr/2015LYO10135/document.
Повний текст джерелаTo date, six million French are hearing impaired. To address this public health issue, efficient tools for exploration of the hearing function are essentials. Speech ABR (Speech Auditory Brainstem Response) is a promising tool, being a fine electrophysiological marker of the neuronal encoding of speech. Though, its methodology remains underdeveloped, its neural origin is still uncertain, and it has never been recorded in hearing aid users. The first axis of this thesis focuses on the neural generators of Speech ABR. The development of a methodology for recording topographies of this response, up to now described as strictly subcortical, first suggested the possibility of a cortical generator. A stereo-electroencephalography study then confirmed the existence of Speech ABR activity in bilateral primary auditory cortices. This result sheds a new light on the representation of speech sounds within the auditory nervous system. The second axis concerns the study of Speech ABR in hearing aid users. After having developed a methodology of acoustic stimulation directly through hearing aids, we investigated neural plasticity induced by hearing aid use. Results show an improvement in the identification of amplified phonemes, linked to an altered cortical representation and a rebalanced frequency encoding. This very first evidence of neural plasticity as soon as the first four months of hearing aid use opens up new therapeutic hopes
Foncelle, Alexandre. "Data-driven computational modelling for some of the implications of dopamine in the brain : From subcellular signalling to area networks." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEI028/document.
Повний текст джерелаIn the brain, the high connectivity level makes it difficult to set up experiments with an appropriate level of control. To address that issue, mathematical models are used to represent the brain in a more comprehensive way. Easier than experiments to test hypotheses, mathematical models can extend them closer to reality and aim to extract the studied principle essence, by simplifying it. Computational modelling is a specific branch of mathematical modelling allowing to solve large numerical calculations. In this thesis, I used computational modelling to study brain parts through different approaches, all in collaboration with neurobiologists and applied to experimental data. A common framework is given by the goal of contributing to a picture of the action of the neuromodulator dopamine. I studied the diversity of dopamine's action at three different scales: the brain region, the cellular level and the molecular level. Dopamine has a large impact on the brain and it is mainly known for its rewarding dimension, it is, indeed, the molecule associated with reward prediction and punishment. Few regions in the brain produce dopamine and these regions are impaired in Parkinson's disease or disrupted in major depressive disorders. Concerning Parkinson's disease, I designed a firing-rate model to fit experimental basal ganglia neural activity, which disclosed significant changes of the neural response between control and Parkinsonian condition. Furthermore, with a Hodgkin-Huxley model accounting for the dynamics of the potassium ion, I could support the hypothesis that the brain region called lateral habenula hyper-activates and induces major depressive disorders because of unbalanced potassium concentration due to astrocyte dysfunction (Kir4.1 channels overexpression). Dopamine is also involved in synaptic plasticity, a phenomenon at the basis of memory that I explored with a third model accounting for several experimental results pertaining to spike-timing-dependent plasticity and its modulation
Elramah, Sara. "Towards a Better Understanding of miRNA Function in Neuronal Plasticity : implications in Synaptic Homeostasis and Maladaptive Plasticity in Bone Cancer Pain Condition." Thesis, Bordeaux 2, 2013. http://www.theses.fr/2013BOR22073/document.
Повний текст джерелаMicroRNAs (miRNAs) are a type of small RNA molecules (21-25nt), with a central role in RNA silencing and interference. MiRNAs function as negative regulators of gene expression at the post-transcriptional level, by binding to specific sites on their targeted mRNAs. A process results in mRNA degradation or repression of productive translation. Because partial binding to target mRNA is enough to induce silencing, each miRNA has up to hundreds of targets. miRNAs have been shown to be involved in most, if not all, fundamental biological processes. Some of the most interesting examples of miRNA activity regulation are coming from neurons. Almost 50% of all identified miRNAs are expressed in the mammalian brain. Furthermore, miRNAs appear to be differentially distributed in distinct brain regions and neuron types. Importantly, miRNAs are reported to be differentially distributed at the sub-cellular level. Recently, miRNAs have been suggested to be involved in the local translation of neuronal compartments. This has been derived from the observations reporting the presence of miRNAs and the protein complexes involved in miRNA biogenesis and function in neuronal soma, dendrites, and axons. Deregulation of miRNAs has been shown to be implicated in pathological conditions. The present thesis aimed at deciphering the role of miRNA regulation in neuronal plasticity. Here we investigated the involvement of miRNA in synaptic plasticity, specifically in homeostatic synaptic plasticity mode. In addition, we investigated the involvement of miRNAs in the maladaptive nervous system state, specifically, in bone cancer pain condition.We hypothesized that local regulation of AMPA receptor translation in dendrites upon homeostatic synaptic scaling may involve miRNAs. Using bioinformatics, qRT-PCR and luciferase reporter assays, we identified several brain-specific miRNAs including miR-92a, targeting the 3’UTR of GluA1 mRNA. Immunostaining of AMPA receptors and recordings of miniature AMPA currents in primary neurons showed that miR-92a selectively regulates the synaptic incorporation of new GluA1-containing AMPA receptors during activity blockade.Pain is a very common symptom associated with cancer and is still a challenge for clinicians due to the lack of specific and effective treatments. This reflects the crucial lack of knowledge regarding the molecular mechanisms responsible for cancer-related pain. Combining miRNA and mRNA screenings we were able to identify a regulatory pathway involving the nervous system-enriched miRNA, miR-124. Thus, miR-124 downregulation was associated with an upregulation of its predicted targets, Calpain 1, Synaptopodin and Tropomyosin 4 in a cancer-pain model in mice. All these targets have been previously identified as key proteins for the synapse function and plasticity. Clinical pertinence of this finding was assessed by the screening of cerebrospinal fluid from cancer patient suffering from pain who presented also a downregulation of miR-124, strongly suggesting miR-124 as a therapeutic target. In vitro experiments confirmed that miR-124 exerts a multi-target inhibition on Calpain 1, Synaptopodin and Tropomyosin 4. In addition, intrathecal injection of miR-124 was able to normalize the Synaptopodin expression and to alleviate the initial phase of cancer pain in mice
Chudotvorova, Ilona. "Rôle de KCC2 dans la plasticité neuronale." Aix-Marseille 2, 2006. http://theses.univ-amu.fr.lama.univ-amu.fr/2006AIX22044.pdf.
Повний текст джерелаChereau, Ronan. "Investigating morpho-functional plasticity of CA3 axons in living brain slices by a combination of STED microscopy and electrophysiology." Thesis, Bordeaux, 2014. http://www.theses.fr/2014BORD0050/document.
Повний текст джерелаMillisecond timing precision in the transfer of information between neurons is essential for the synchrony and plasticity of neural circuits in the brain. Axons are neuronal extensions that ensure the communication via brief electrical impulses called action potentials (AP). Because they are unmyelinated and are extremely thin, hippocampal axons propagate APsslowly and thus generate long delays of conduction (up to 100 ms) that are traditionally considered invariant. However, recent studies have shown that activity changes the morphology of axons and modulate the latency of transmission, thus raising the question whether axons undergo activity-dependent structural changes that could influence the propagation of APs. The diameter of hippocampal axons (ranging between 100-350 nm) are usually too thin to be properly resolved by conventional light microscopy. However, the development of super resolution STED imaging now enables the observation of their detailed morphological dynamics in living tissue. Using a novel combination of STED microscopy, field recordings, patch-clamp electrophysiology in mouse brain slices and computer simulations we discovered that CA3 axons undergo long-lasting enlargement in their diameter after the induction of long term potentiation (LTP). We provide strong evidence that this diameter enlargement increases AP conduction velocity. Taken together, our findings indicate that axons can dynamically tune AP propagation delays by changing their diameters, thereby altering the timing of information transfer in neural circuits. This study suggests a novel and powerful structural mechanism for neural plasticity
Fourrier, Celia. "Bases neurobiologiques des troubles de l'humeur et de la cognition associés à l'obésité : rôle de l’inflammation." Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0359/document.
Повний текст джерелаObesity is a metabolic and inflammatory disorder that represents a major risk factor for the development of comorbidities such as type 2 diabetes. Obese patients also often experience mood and cognitive dysfunctions that represent important risk factors for aggravation of obesity and related outcomes. Reducing the development of such alterations may therefore allow improving health and quality of life of obese subjects. In this context, this thesis aimed to decipher the neurobiological mechanisms underlying such neuropsychiatric alterations, in order to identify new targets for the development of potential preventive and/or therapeutic strategies aiming to reduce these alterations. To do so, rodent models of obesity such as the db/db mice, which display severe obesity associated with classical features of metabolic syndrome, can be particularly useful.[ ] Second, we have investigated whether a nutritional intervention with n-3 polyunsaturated fatty acids (n-3 PUFAs) and antioxidants, which are well-known to display anti-inflammatory and neuroprotective properties, improved obesity-associated neuropsychiatric alterations. In addition, we have measured the consequences of chronic administration of the prebiotic oligofructose on the behavioral alterations displayed by db/db mice since previous studies pointed to the gut microbiota as an important player in the regulation of behavior. Finally, we have investigated the potential underlying mechanisms by measuring the impact of this treatment on the metabolism and systemic inflammation, but also on neurobiological systems known to be involved in the control of food intake and behavior. We first showed that an anti-inflammatory treatment or caloric restriction reduced anxiety-like behaviors, and this was associated with a selective decrease of hippocampal TNF-α mRNA expression, suggesting that this pro-inflammatory cytokine likely contributes to induce anxiety-like behavior associated with obesity. We then nicely confirmed this assumption by showing that selectively blocking brain TNF-α by chronically administrating etanercept i.c.v. (TNF-α decoy receptor) indeed decreased anxiety-like behaviors in obese db/db mice.[ ] Secondly, we tried identifying new preventive and/or therapeutic strategies aiming to improve mood and cognitive alterations associated with obesity. Hence, we measured if an n-3 polyunsaturated fatty acids/antioxidants enriched diet, well-known to modulate different neurobiological mechanisms potentially involved in behavioral alterations displayed by db/db mice, improved their behavioral alterations. We showed that chronic consumption of this diet reversed hippocampus-dependent spatial memory deficits displayed by db/db mice in a water-maze task and that this effect likely involved modulation of neuronal plasticity. Thirdly, we tested whether manipulating the gut microbiota composition may constitute a preventive and/or therapeutic strategy to improve the neuropsychiatric alterations associated with obesity. Hence, we assessed for the first time the effect of microbiota manipulation with a prebiotic on the metabolic and behavioral alterations displayed by db/db mice, but also on their systemic and neurobiological correlates. We showed that improvement of metabolic alterations following prebiotic administration in db/db mice was associated with selective reduction of peripheral and central inflammation, which is however not accompanied by detectable improvement of anxiety-like behavior or spatial memory deficits. To conclude, these experiments contribute to show that inflammation, and especially TNF-α, could be an important target to develop therapeutic treatments for mood alterations associated with obesity, whereas nutritional interventions with selective nutrients of interest may rather help preventing associated metabolic and/or cognitive alterations
Denizet, Marie. "Rôle de la microglie dans la neurogenèse adulte, dans le bulbe olfactif de la souris." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066391/document.
Повний текст джерелаMicroglia are resident immune cells in the central nervous system. They participate in the pruning of developing neurons. Complement factors are key markers of the dendritic spines to eliminate
Bosch, Karen. "Studies of plasticity after neuronal injury." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/studies-of-plasticity-after-neuronal-injury(862757df-95eb-4c1f-8c58-ce4f2657c63c).html.
Повний текст джерелаYger, Pierre. "Chaos control and plasticity in large scale neuronal networks with ongoing activity." Paris 11, 2010. http://www.theses.fr/2010PA112362.
Повний текст джерелаUnderstanding how the primary sensory areas of the neocortex are structured in order to process sensory inputs is a crucial step in analysing the mechanisms underlying the functional role, from an algorithmic point of view, of cerebral activity. This undrestanding of the sensory dynamics, at a large scale level, implies using simplified models of neurons, such as the integrate-and-fire models, and a particular framework, the balanced network, which allows the recreation of dynamical regimes of conductances close to those observed in vivo, in which neurons spike at low rates and with an irregular discharge. This thesis shows, using large scale simulations and particular patterns of stimulation whose statistics are close to those of the spontaneous activity, that such neuronal networks in asynchronous and irregular firing states, such as the primary visual cortex in vivo can operate at the border of a particular dynamical regime, deterministic chaos. While the ongoing activity of those networks with random or structured connectivity is often considered as noise, its structure, emmerging from the recurrent connectivity, could have a functional role in information processing. To modulate the statistics of such an activity, and to see if a trace of this learning is kept in the ongoing activity in the framework of unsupervised learning, the connectivity within the neuronal network must evolve as a function of the activity. A new rule of plasticity was therefore explored, incorporating some homeostatic constraints in the framework of metaplasticity. This hypothesis can link different theorical schemes of plasticity by the definition of a biophysically realistic mechanism
El, Hasnaoui Raja. "Adaptations cérébrales chez un modèle de souris déficientes en érythropoiétine acclimatées à l'hypoxie." Paris 13, 2008. http://www.theses.fr/2008PA132015.
Повний текст джерелаPolycythemia and the increase in ventilation are considered as the major factors of acclimatization to hypoxia. However, erythropoietin deficient mice (Epo-TAgh) survive to 14 days at 4200 m despite severe anemia probably through the increase in their ventilation in normoxia as well as in hypoxia. The mechanisms underlying the oxygen delivery, particularly in the brain of thèse mince were questionned in our works. We hypothesized that the factors implied in the central control of the ventilation, in the cerebral blood flow and the cerebral angiogenesis could be increased in normoxia and that they would be overexpressed after chronic hypoxia. We should that ventilatory aclimatization in hypoxia, in control mice is mediated through medullary NMDA receptors and neuronal NOS leading to NO production which could regulate ventilation. In anemic mice, noroxic hyperventilation could be partially mediated through NMDA receptors and probably through Epo receptors, while the mechanisms of their ventilatory acclimatization in hypoxia remained to be determined. In addition, anemic mice in normoxia compensate Epo deficiency by an increase in the cerebral cortical angiogenesis mediated by HIF-1/VEGF signalisation, while Epo receptors and Jak2/STAT-5 pathway could mediate neuroprotection as well as angiogenesis. In chronic hypoxia, wild type mice acclilmatize through polycythemia and cerebral ngiogenesis, while in Epo-TAgh mice, only NO metabolites were greatly increased, suggesting either a higher cerebral blood flow, or NO cytotoxicity which could lead to cerebral lesions. In conclusion, cerebral plasticity occurs following chronic anemia as well as chronic hypoxia to maintain or increase the oxygen delivery. I addition, molecular, biochemical and morphological studies in the anemic and hypoxic brain could be of interest to understand the physiopathology of the lack of oxygen delivery to the brain. Furthermore, the comparison of results obtained in the brain with the mechanims underlying oxygen delivery to the heart but also to the muscles could enhance the knowledge of the mechanisms of acclimatization to hypoxia in the lack of Epo
Coquillat, Delphine. "Les groupements polysialiques : cibles d'un vaccin contre le méningocoque B et déterminants de la plasticité neurale." Aix-Marseille 2, 2001. http://www.theses.fr/2001AIX22013.
Повний текст джерелаVallortigara, Julie. "Etude des effets de l'hypothyroïdie sur les voies d'action cellulaire de l'acide rétinoïque et de la triiodothyronineApproches expérimentale et biomédicale." Bordeaux 1, 2007. http://www.theses.fr/2007BOR13395.
Повний текст джерелаSeveral works permit to establish a relationship between activity of retinoic acid (RA) pathway and memory performance. Recent data obtained in vitamin A deficient (VAD) animals, comparable to those obtained in aged animals, have revealed that RA promnesic effect in brain tissues could depend on thyroid hormone status. Indeed, in these models, triiodothyronine (T3) becomes a limiting factor alone able to correct the age or VAD-related concomitant hypo-activation of retinoid and thyroid signalling and alterations of synaptic plasticity. The aim of the present study was to investigate the effects of hypothyroidism on RA and T3 cellular action in adult mice brain. Our results show that hypothyroidism led to a reduced expression of T3 nuclear receptors (TRβ) and their target genes (RC3, Rhes, CaMKII) preferentially in the striatum. RA administration has no incidence in our model, confirming an impaired function of RA with hypoactivity of T3 signalling. In addition, T3 administration permitted a restoration of molecular parameters studied, and modified phospho-Thr34 DARPP-32 protein level, a reliable indicator of synaptic plasticity involved in motor functions. A study using transgenic animals has revealed that normalization of synaptic target genes by the T3 necessitates the presence of the receptor TRα. These results provide new data regarding the molecular basis of thyroid hormone action in the synaptic plasticity process. A biomedical approach performed on peripheral blood mononuclear cells of hypothyroid patients allowed us to confirm in humans the relevance of the relationship between retinoid and thyroid signalling pathways during common thyroid disorders
Djerbal, Lynda. "Caractérisation de l'interaction semaphorine 3A-chondroïtine sulfate dans le système nerveux central." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV041/document.
Повний текст джерелаPerineuronal nets (PNNs) are the key regulators of neuronal plasticity and regeneration in the mature central nervous system (CNS). They are a unique and highly organised extracellular matrix (ECM) structure, found around sub-population of neurons, composed mainly of chondroitin sulfate proteoglycan (CSPG). Chondroitin sulfate (CS) is a linear polysaccharide belonging to glycosaminoglycans (GAGs) family. The sulphation pattern defines different types of CS, which interact with different signalling proteins including those regulating axonal outgrowth and guidance such as semaphorin 3A (Sema3A). Sema3A is a secreted chemorepulsive protein found accumulated in the PNNs through its interaction with CS. This process is believed to potentiate Sema3A signalling through plexin A1 (PlxnA1) and Neuropilin 1 (Nrp1) and regulate plasticity and regeneration. The aim of the thesis project is to characterise the interface of Sema3A- CS interaction.For this purpose, Sema3A is expressed in eukaryote cells and purified. Interestingly, two major forms were obtained: a full length Sema3A (90 kDa) which remains attached to the cell surface GAGs and a truncated form without the C-ter part (65 kDa) which is released to the culture medium. With the use of surface plasmon resonance (SPR), we observed that full length Sema3A binds selectively to CS-E (4,6-disulfated chondroitin) and heparan sulfate with a high affinity (KD in the sub pM range), while the truncated Sema3A does not bind to any GAG. Four putative GAG binding sequences were identified in the C-ter of Sema3A and mutated using site directed mutagenesis. SPR analysis then revealed that two out of these four sites are required for the binding to CS-E. The importance of these GAG-binding sequences in inhibition of neurites outgrowth of dorsal root ganglion neurons in culture was also reported, indicating thus the importance of GAG-binding in Sema3A signalling. In parallel, the minimal required sequence of Sema3A-binding of CS-E was determined as being a tetrasaccharide. The Sema3A-CS interface was thus characterized. Furthermore, quartz crystal microbalance with dissipation monitoring analysis suggested that Sema3A could crosslink GAG chains. This suggests Sema3A could be involved in stabilising the PNN network and induces mechanical changes on neuronal surface.The detail characterization of Sema3A-CS interaction may enable the design of new strategies aiming at enhancing plasticity and regeneration for neurodegenerative diseases or spinal cord injury
Nguyen, Hien luong. "Plasticité, métaplasticité synaptique et neuronale dans le cortex somatosensoriel primaire chez le rat dans un modèle de douleur inflammatoire prolongée." Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAS027.
Повний текст джерелаChronic neuropathic or inflammatory pain is believed to result from long-lasting synaptic andneuronal changes in pain pathways, including the primary somatosensory cortex (S1) which codes for pain intensity and location. Using ex vivo electrophysiological recordings from S1 layer 2/3 pyramidal neurons, we investigated pain-induced plasticity in a rat model (CFA injection) of chronic facial inflammatory pain. We first establish the relation in basal conditions between synaptic activity and (i) bidirectionalsynaptic plasticity (long-term depression/potentiation; LTD/LTP), (ii) changes in the ability to express synaptic plasticity (metaplasticity), (iii) bidirectional changes in intrinsic neuronal excitability (LTP/LTD-IE); i.e. the rules for synaptic and intrinsic plasticity in S1 layer 2/3pyramidal neurons. We then investigated such plasticity processes in CFA-treated rats exhibiting facial mechanical allodynia, at 1 hour and 3 days post-injection. At 1-hour, mechanical allodynia is associated with (i) LTP of excitatory synaptic transmission, together with (ii) an inhibition to generate further LTP but a facilitation to generate LTD (metaplasticity), consistent with LTP of synaptictransmission, (iii) LTP-IE and (iv) reduced dendritic arbor complexity of S1 layer 2/3 pyramidal neurons. At 3 days, LTP and LTP-IE were still present but metaplasticity and dendritic arbor complexity had returned to control levels
Bjartmar, Lisa. "Pharmacological and Developmental Aspects on Neuronal Plasticity." Doctoral thesis, Linköpings universitet, Geriatrik, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-51450.
Повний текст джерелаAubert, Isabelle. "Cholinergic markers in models of neuronal plasticity." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28417.
Повний текст джерелаThese markers of the cholinergic synapse are differentially affected depending upon the model studied. In addition, pre- and postsynaptic cholinergic markers are not necessarily altered similarly. For example, muscarinic M$ sb2$ and nicotinic sites decreased in parallel with ChAT activity in the neocortex and hippocampal formation of human brain patients suffering from neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. However, in the aged memory-impaired rats, ChAT activity and nicotinic sites are unaltered while muscarinic M$ sb2$ sites are significantly increased in cortical areas. Moreover, although AChE staining is increased in the hippocampal formation following lesions of the entorhinal cortex, nicotinic binding sites are decreased and other cholinergic markers are unaffected. Finally, during rat brain development, presynaptic markers such as the acetylcholine vesicular transport and nicotinic sites are expressed prenatally, while others like ($ sp3$H) HC3 and muscarinic M$ sb2$ sites appear only postnatally. Muscarinic M$ sb1$ sites are in low amounts prenatally, increasing gradually during postnatal maturation. The distinct ontogenic profile of each cholinergic marker suggests specific roles for the various components of the cholinergic synapse throughout brain development.
Taken together, these results provide information on the differential adaptation, response and possible roles of the various components of the cholinergic synapse in models of neuronal plasticity. For example, nicotinic receptors may play an important role in the development, sprouting and maintenance of a normal cholinergic innervation, while muscarinic M$ sb2$ receptors might contribute to the fine regulation of ACh release, which, if impaired, could produce detrimental effects on cognitive functions such as those seen in the aged memory-impaired rats.
Romand-Monnier, Margaux. "Functional and structural brain adaptations to changing and uncertain environments in humans." Thesis, Université de Paris (2019-....), 2019. http://www.theses.fr/2019UNIP7117.
Повний текст джерелаIn a world characterized by stochasticity, volatility and ambiguity, efficiently adapting to the environment uncertainty is absolutely crucial. Such adaptation takes place over a continuum of timescales; from the tens of milliseconds necessary for neurons to modulate firing rates, to the weeks allowing structural brain changes, to the millennia needed for the complex reorganization of the brain anatomy and function like the one observed in primate evolution. In this thesis, we tackle brain adaptations to uncertain and changing environments at two different timescales. First, we investigate the fast and short-term brain functional modulations allowing adaptive decision-making behaviour in response to sudden changes in the environment. In a two-armed bandit task comprising various levels of volatility, we show that a simple inference model assuming stable external contingencies but with computation imprecisions following the psychophysical Weber law, hereafter inference noise model, performs virtually as well as the optimal Bayesian adaptive process inferring the volatility of the environment. We also establish that this inference noise model better accounts for human behavioural performance in changing environments than the optimal Bayesian one. Using model-based fMRI analyses, we show that the anterior cingulate cortex (ACC) activations, previously associated with the volatility inferred from the optimal Bayesian model, rather reflect inference noise. Our results suggest that humans ability to adapt in a changing environment partly stem from Weber-structured inferential noise rather than from complex probabilistic inference of the environment volatility. In the second part of this work, we study how slow and long-lasting brain structural adaptations, also known as brain plasticity, go along with adaptive behaviour in new and uncertain environments at a scale of weeks. To investigate this issue, brain structural MRIs were obtained for a 44-year-old male subject, who left his regular life environment for four one-month expeditions in extremely challenging and harsh environmental conditions. Physical challenges stemmed from trekking in extreme temperatures and degrees of humidity. In addition, the subject faced great emotional and social challenges resulting from social deprivation, as he spent these expeditions in complete social isolation. Comparison of structural images before and after expeditions using voxel-based morphometry (VBM) analysis revealed significant changes of gray matter (GM) density in well-known regions involved in motor functions, perception, higher cognition and social cognition networks. This longitudinal case study findings show that brain structural adaptations go beyond the well-known and characterized plasticity associated with learning, by revealing brain changes in response to environmental demands, rather than task demands. This suggests that brain plasticity can happen when the environment over- or under-solicits specific functions, beyond the repetition of specific tasks. These findings are based on a single subject data, and future research should investigate whether this structural plasticity generalises to the population
Nadeau, Gabriel. "Imagerie optique de la plasticité synaptique." Master's thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/27375.
Повний текст джерелаClassical measurements of synaptic plasticity have involved electrophysiological methods which provide high sensitivity for detecting small changes in synaptic strength. However, this approach does not provide much information about the location of the synapses that undergo plastic changes. Because synaptic plasticity can be synapse-specific, having the ability to monitor changes in synaptic strength at individual synapses is important in order to enable simultaneously monitoring of local molecular mechanisms associated with the plasticity. New fluorescent tools developed in the last decades allow to directly visualize synaptic activity, signaling, and remodeling at individual synapses. During my Master studies, I used optical imaging of a genetically-encoded calcium (Ca2+) sensor, GCaMP6f, to record miniature synaptic Ca2+ transients (MSCTs) in cultured rat hippocampal neurons. For these experiments, I performed video-microscopy on neurons perfused with external solution lacking Mg2+ and containing Tetrodotoxin (0Mg2+/TTX). I have observed highly localized and transient increases of intracellular Ca2+ in dendritic compartments and spines. To test whether these MSCTs can be potentiated, I have measured them before and after a 5 min stimulation known to induce plasticity in cultured neurons (0Mg2+/Glycine/Bicuculline, cLTP). A lasting increase in the frequency and amplitude of MSCTs, for at least an hour, arose from this stimulation protocol. I have thus investigated the molecular mechanisms of this plasticity. The MSCTs are mostly mediated by NMDA receptors, since they are almost totally blocked by the selective antagonist to the receptor, AP5. Moreover, addition of AP5 only during the cLTP stimulation blocks the MSCT plasticity. It thus appears that both the MSCTs and their plasticity are NMDA receptor-dependent. Interestingly, the MSCTs and their plasticity are not blocked by the AMPA receptor antagonists NBQX, pointing to possible changes in NMDA receptor content, postsynaptic Ca2+ signaling, or presynaptic neurotransmitter release. Also, while we found that CaMKII signaling is non-essential for the induction of the plasticity, preliminary data are showing a plausible PKA-dependency of the plasticity. To test these hypotheses, I have also tried to combine Ca2+ imaging with imaging of other pre and postsynaptic components, to identify the molecular mechanisms responsible for the MSCT plasticity. Overall, this new approach presented in this thesis might provide new knowledge on the diversity of molecular processes that support synaptic potentiation.
Rech, Fabien. "Les bases neurales du contrôle moteur : étude des réseaux moteurs négatifs par cartographie cérébrale cortico-sous-corticale." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT050.
Повний текст джерелаThe classical and hierarchical view of the motor system has been challenged since the discovery of other structures able to modulate the motor output in the framework of a hodotopic model. The aim of this work was to study the motor control network thanks to direct electrostimulations performed during awake surgery for brain tumors. This method has shown its effectiveness to preserve motor functions while giving new highlights about the organization of the motor system. In our work, motor control has been studied through the negative motor phenomenon, which consists in a complete arrest of movement without loss of tonus or consciousness during electrostimulations. Initially described at a cortical level, our work demonstrated the possibility to elicit negative motor phenomenon in both hemispheres at a subcortical level. Moreover, we identified a bilateral modulatory motor pathway able to inhibit both upper limbs during unilateral subcortical stimulations. We also shown that fibers driving negative motor responses are organized in a somatotopic manner, like the pyramidal pathway. Resection of these fibers lead to a supplementary motor area syndrome with permanent deficit in fine motor skills and bimanual coordination. These results explain the neurological deficits which might occur after surgery in premotor areas when no active brain mapping is performed, that is, when only primary motor structures are sought. They emphasize the necessity to perform a motor mapping during awake surgery whatever the side and hemispheric dominance. These subcortical results led us to define the concept of negative motor networks and their involvement in motor control networks. Evidences of this network allowed us to explore the cortical level and to report a well-defined organization of the negative motor area, different from the random or somatotopic distributions previously described. This effector-dependent and redundant organization in several areas defined by direct electrostimulations has been helpful to confirm the rostro-caudal and dorso-ventral segregation of the precentral gyrus. Consequently, it was possible to propose several hypothesis about the role of these networks. We presume that they are constituted by several large-scale interconnected networks, based on internal inhibitor mechanisms, whose role goes from modulation of the motor output in a competitive model of decision-making integrated in the negative motor area to real inhibition of motor behaviors thanks to cortico-basal ganglia circuitry. The probabilistic map created with these works will be helpful to plan surgery but could also provide regions of interest for brain stimulations therapies as well as neuroscientific research
Valentinova, Kristina. "Synaptic plasticity in the lateral habenula controls neuronal output : implications in physiology and drug addiction." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066743/document.
Повний текст джерелаThe capacity of the brain to anticipate and seek future rewards or alternatively escape aversive events allows individuals to adapt to their environment. A considerable research effort has focused on unraveling the cellular and synaptic mechanisms within the meso-cortico-limbic system underlying motivational processing both in physiological conditions and in pathologies such as addiction and depression. However, only recently we begin to understand the circuit substrates capable to control midbrain monoaminergic nuclei and their contribution to motivated behaviors. The Lateral Habenula (LHb) has emerged in the last decade, as a major player encoding stimuli with motivational value and in controlling monoaminergic systems. The wiring of this epithalamic structure subserves discrete features of motivated behaviors, including preference and avoidance. Recent advances have also demonstrated that aberrant modifications in LHb function trigger negative emotional states in disorders including depression and addiction, highlighting the LHb as an important brain target for therapeutic intervention for these pathological states. In my thesis work I first sought to investigate how modulation of synaptic transmission in the LHb controls neuronal activity, especially focusing on the role of metabotropic glutamate receptors. In a second study, I expanded my work examining how drug experience changes synaptic transmission in a precise habenular circuit that we discovered to be crucial for depressive states during cocaine withdrawal. In an initial data set, we found that, in the LHb, metabotropic glutamate receptor 1 activation drives a PKC-dependent long term depression of excitatory (eLTD) and inhibitory (iLTD) synaptic transmission. Despite the common induction, eLTD and iLTD diverged in their expression mechanism. While eLTD required endocannabinoid-dependent reduction of glutamate release, iLTD expressed postsynaptically through a decrease of β2-containing GABAA receptors function. Further, eLTD and iLTD bidirectionally controlled LHb neuronal output. In a second study, we showed that chronic cocaine exposure leads to a persistent and projection-specific increase of excitatory synaptic transmission onto LHb neurons. This form of synaptic potentiation required membrane insertion of GluA1-containing AMPA receptors and a reduction in potassium channels function ultimately leading to increased LHb neuronal excitability both in vitro and in vivo. These cocaine-driven adaptations within the LHb were instrumental for depressive-like states emerging after drug withdrawal. Altogether this work demonstrates how synaptic plasticity in the LHb affects neuronal output and thereby contributes to behaviors associated with the pathology of motivation
Zeeni, Nadine. "Plasticité neuronale des voies périphériques et centrales contrôlant la prise alimentaire." Paris, AgroParisTech, 2009. http://www.theses.fr/2009AGPT0065.
Повний текст джерелаMensch, Maria. "Étude du rôle pathophysiologique des peptides Aη récemment découverts dans le cerveau". Electronic Thesis or Diss., Université Côte d'Azur, 2020. http://theses.univ-cotedazur.fr/2020COAZ6001.
Повний текст джерелаThe amyloid precursor protein (APP) is well known by its association with Alzheimer's disease (AD), the most common neurodegenerative disease worldwide. Despite intense research focusing on AD over the last 30 years, the progress in understanding its etiology and finding a cure has been limited. Thus far, all data gathered regarding the genetic causes of familiar AD, the progression of the disease, and potential therapeutic targets for AD, highlight the importance of APP and its cleavage products. Deciphering the role of the different APP fragments in synaptic function and behavior is crucial to understand AD etiology fully. In 2015, Willem et al., described a new APP processing pathway producing amyloid-η (Aη) peptides. They could demonstrate that the Aη-α peptide, the longest form of Aη produced by η-secretase and α-secretase cleavage, harbors bioactive properties. Applied on the hippocampus ex vivo it lowers long-term potentiation (LTP) and in vivo it lowers calcium wave activity. Going beyond these initial observations, my thesis, "Unraveling the physiopathological role of the newly discovered Aη peptides in the brain" focused on further identifying Aƞ-α actions on different parameters of excitatory synaptic plasticity and associated behavioral outputs. We tested the effects of acute and chronic elevations of Aƞ-α, employing acute application of synthetic Aƞ-α (M108) on hippocampal slices ex vivo or via the analysis of new transgenic mouse lines MISEPA2 and MISEPA4 overexpressing Aƞ-α, respectively. Our results show that Aη-α impacts synaptic plasticity at low nanomolar concentrations and shifts plasticity towards long-term depression (LTD), while it does not perturb pre-synaptic short-term plasticity or basal synaptic transmission. Next, to unravel the effects of both acute and chronic elevated Aƞ-α levels on cognition, we performed a series of memory-dependent behavioral tests. Analysis of the transgenic mouse lines indicated no major memory impairments, although subtle alterations were noticeable upon individual testing and analysis paradigms. Also, an acute injection of M108 in the brain in vivo did not correlate with significant memory loss. We conclude that, while hippocampal excitatory synaptic plasticity is clearly impacted by elevated Aη-α levels, this cellular phenotype failed to robustly translate into alterations of behavioral output thus far. In parallel, we went on to investigate the effects on synaptic plasticity and behavior caused by the absence of APP processed by ƞ-secretase in a novel knock-out APPΔEta mice line. In this mouse line LTD could not be induced, but acute M108 application rescued this phenotype. These data reveal a crucial role of Aη-α in this synaptic plasticity mechanism. Additionally, APPΔEta mice exhibited impaired spatial memory in MWM task and reduced anxiety in the Open field and Light-Dark box tests, indicating that this APP cleavage is necessary for cognitive functions. In conclusion, our results advanced the understanding of the physio-pathological role of Aƞ in the brain, highlighting an essential function in excitatory synaptic plasticity and cognition
Cui, Yihui. "The many faces of corticostriatal spike-timing dependent plasticity." Paris 6, 2013. http://www.theses.fr/2013PA066398.
Повний текст джерелаThe corticostriatal plasticity is thought to be the neuronal substrate of procedural learning. We first investigated non-hebbian plasticity and found that both depolarization-induced suppression of excitation (DSE) and low-frequency stimulation (LFS) protocols induced LTD and are both mediated by endocannabinoid (eCB)-signaling. We then focused on corticostriatal spike timing-dependent plasticity (STDP) characterization and robustness. We found that with 100 STDP pairings, corticostriatal LTP was NMDA-dependent while LTD involved eCB-signaling. We then tested the robustness of corticostriatal STDP. We uncovered that LTP was even inducible with 5 pairings. Thanks to a model-driven experiment strategy, we demonstrated that this LTP relies on eCB-signaling. This eCB-LTP is homosynaptic, depends on cannabinoid-type-1 receptor (CB1R) and transient receptor potential vanilloid-type-1 (TRPV1) activation and is supported by presynaptic PKA and calcineurin. Our results considerably enlarge the spectrum of action of eCBs since they show that eCBs promote not only depression but also potentiation. To investigate the limits of corticostriatal STDP, we varied the STDP rate. We observed a transition from timing- to rate-dependent plasticity. This rate-dependency exists with both 100 and 10 pairings, in which LTP is respectively NMDA-dependent and CB1 and NMDA receptors. We then applied a randomized jitter within STDP protocol. We showed that NMDA-LTP is highly sensitive to jitter while eCB-LTP is not. These results showed novel forms of corticostriatal plasticity and demonstrated that the multiple learning rules at play for governing the corticostriatal information processing
Akchiche, Nassila. "Conséquences d'une carence en donneurs de méthyles sur la différenciation cellulaire, la survie et la neuroplasticité : approches mécanistiques in vitro sur des lignées neuronales." Thesis, Nancy 1, 2009. http://www.theses.fr/2009NAN10122/document.
Повний текст джерелаFolate (vitamin B9) and vitamin B12 act as cofactors in the one-carbon metabolism that regulates transmethylation reactions involved in epigenetic mechanisms. A deficiency in folate and/or B12 decreases the generation of methionine from homocysteine, a toxic amino acid that has been associated with pathologies of the central nervous system at all ages (spina bifida, Alzheimer's disease…). In order to depict the cellular and molecular mechanisms implicated in the response to the deficiency in these micronutrients, two new cell models have been developed. Thus, we have analyzed the effects of folate deficiency on proliferation, differentiation and neuroplasticity of neuronal progenitors obtained from the hippocampus of rat embryos, i.e. the H19-7 cell line. Regarding the second model, we designed an original approach by stable transfection of NIE-115 murine neuroblastoma cells to impose the anchorage of a chimeric B12 binding protein, transcobalaminoleosin (TO) to intracellular membrane in order to produce intracellular sequestration of B12. Taken together, our results have shown that deficiency-associated alterations of the one-carbon metabolism lead to reduced neurogenesis and to dramatic impairment of neuron differentiation. This suggests the existence of specific mechanisms through which vitamin B9/B12 deficiency and/or homocysteine may affect brain functioning and plasticity
Luckman, Simon M. "Neuronal-glial interactions in the neurohpophysis." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334212.
Повний текст джерелаBensmail, Boughediri Soraya. "Modélisation neuromimétique du contrôle sensori-moteur des mouvements du membre supérieur : cas du pointage et de la saisie." Versailles-St Quentin en Yvelines, 2005. http://www.theses.fr/2005VERS0032.
Повний текст джерелаThe advanced ones in motor control research attract the scientists of disciplines other than the neurophysiology. Thus, the robotics researchers also adhere to these programs. Their aim is to elaborate new neuromimetic command rules inspired from the SNC executiong motor action. A model of sensorimotor control is developed for visuo-guided movements learning. This model is developed based on several prerequisites about "computational" principles of brain structures : the columnar organization of the cerebral cortex and the Marr-Albus-Ito theory of cerebellar learning. The adaptive rules incorporeted in the model simulate the synaptic plasticities localised in various sites of the CNS : cerebral cortex and cerebellum. This connexionist approach is applied to simulate learning of the "arm" visuo-guided movements and the "thumb-index" pinch. The neural network model consists of two hierarchical levels : the high level which generates motor orders to muscles activation and the spinal level producing musculo-skeletal structure displacements. Thus, muscular forces are generated according to the Equilibrium-Point-Hypothesis. The simulation of the non linear formalism shows that adaptive processes taking place in different sites of the total neural network model cooperate without interferer. For the movement of "thumb-index" grip , we propose that the neural network model is deployed by considering two fingers structure. So the cortical level is presented by two pathways controlling two working points and only one cerebellar network may be able to coordinate the global pinch movement
Amad, Ali. "Étude de la plasticité cérébrale en psychiatrie à partir de plusieurs modèles pathologiques : le trouble de personnalité borderline et les hallucinations." Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S034/document.
Повний текст джерелаThe study of the neuroplasticity (NP) has been emphasized to improve the comprehension of pathophysiology of psychiatric disorders, including biomarkers for predicting and monitoring treatment response. NP can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections and can be described from a translational perspective at many levels, from molecular to cellular to systems to behaviour. Psychiatric disorders are characterized by a high degree of heterogeneity (pathophysiological, etiologic and clinical levels) which can be conceived as an advantage when examined from the perspective of the NP. In fact, psychiatric disorders can be used as models to study the different aspects of the NP.Individual-dependent plasticity−The lack of susceptibility genes related to several psychiatric disorders may be due to tendency to look for genetic effects on disease rather than genetic effects on vulnerability to environmental causes of disease. In fact, \\\"vulnerability genes\\\" may function more like \\\"plasticity genes\\\", resulting in greater susceptibility of individuals to both positive (e.g., environmental support and enrichment) and negative (e.g., childhood maltreatment) facets of environmental experiences. This concept has been proposed in an integrative model of a frequent psychiatric disorder : the borderline personality disorder (BPD). Age-dependent plasticity−There are qualitatively and quantitatively different changes in the brain in re¬sponse to what appears to be the same experience at dif¬ferent ages. This aspect of NP has been studied by using the \\\"Borderline Personality or Complex Posttraumatic Stress Disorder controversy\\\" with a genetic association study, with independent replication, on genes associated with the physiological response to stress in the hypothalamic–pituitary–adrenal (HPA) axis. Symptom-dependent plasticity−Adaptative neuroplastic modifications in the structure and function of the human brain in response to environmental demands have been showed in numerous situations in healthy controls. Interestingly, NP have also been associated to adaptation to pathology in several psychiatric disorders. A recent example has been provided by the study of visual hallucinations in schizophrenia patients. Hallucinations can be defined as perceptions in the absence of external stimuli. In schizophrenia, hallucinations constitute the most typical and disabling symptoms of the disorder and may manifest in all sensory modalities. Several MRI findings support the hypothesis that distinct patterns of connectivity, particularly within networks involving the hippocampal complex (HC), could be associated with different hallucinatory modalities. The aim of our study was to investigate HC connectivity as a function of the hallucinatory modality, i.e., auditory or visual in two carefully selected subgroups of schizophrenia patients with only auditory hallucinations (AH) or with audio-visual hallucinations (A+VH). Hippocampal volume and shape analysis showed localized hippocampal hypertrophy in the A+VH group. These structural findings indicate that plastic changes are associated with hallucinations. Indeed, the hippocampus is capable of plastic deformation, and the present findings are consistent with experience-dependent shape modifications of the hippocampus that involve mechanical tension along the axon.This PhD thesis highlights several arguments that the NP perspective provide new insights to the pathophysiology, to improve and emphasize therapeutic innovation of psychiatric disorders