Dissertations / Theses on the topic 'Mechanoreception'

The American alligator (Alligator mississippiensis) is an aquatic diving reptile with a periodic breathing pattern. Previous work has identified pulmonary stretch receptors (PSR), both rapidly- and slowly-adapting, and intrapulmonary chemoreceptors (IPCs) that modulate breathing patterns in alligators. The purpose of the present study was to identify the effects of prolonged lung inflation and deflation (simulated dives) on PSR and/or IPC firing characteristics in the alligator. The effects of airway pressure, hypercapnia, and hypoxia on dynamic and static responses of pulmonary stretch receptors (PSR) were studied in juvenile alligators (mean mass = 246 g) at 24°C. Receptor activity appeared to be a mixture of slowly-adapting PSRs (SARs) and rapidly-adapting PSRs (RARs) with varying thresholds and degrees of adaptation, but no CO2 sensitivity. Dives were simulated in order to character receptor activity before, during, and after prolonged periods of lung inflation and deflation. Some stretch receptors showed a change in dynamic response, exhibiting inhibition for several breaths after 1 min of lung inflation, but were unaffected by prolonged deflation. For SAR, the post-dive inhibition was inhibited by CO2 and hypoxia alone. These airway stretch receptors may be involved in recovery of breathing patterns and lung volume during pre- and post-diving behavior and apneic periods in diving reptiles. These results suggest that inhibition of PSR firing following prolonged inflation may promote post-dive ventilation in alligators.

Using three-dimensional Schlieren-based videography, males of the freshwater alpine species Hesperodiaptomus shoshone (Wyoming) were found to follow both conspecific females and conspecific males, remaining 0.45 ± 0.13 cm (male) and 0.56 ± 0.13 cm (female) from the lead copepod for 0.91 ± 0.35 seconds (male) and 0.84 ± 0.46 seconds (female). Trail following is initiated when the male makes a rapid reorientation. Chemical pheromones either were not produced by the female or were not detected by the male because males would follow trail mimics composed of female-conditioned water. Using unconditioned water, males were found capable not only of following trail mimics but they showed a preference, quantified as a higher follow frequency, of trails running at speeds matching that of their female mate. Remarkably, the male copepods always followed upstream, micro-casting between the edges of the trail to remain on track. Trails flowing at speeds matching their mate’s swimming speed were followed for a longer period of time and at greater gross distance. As the flow speed of the trail mimic increased, the distance the copepod would advance would decrease until the threshold speed of 2.30 cm/sec at which it would not follow a trail and only station hold. Station holding has never been observed before for copepods and may represent an adaptive behavior to avoid being washed out of their resident alpine pond. At speeds greater than that evoking station holding, the stream seemed to push the copepod out of the flow even though the copepod would make repeated efforts to swim up the stream. This research revealed a behavior not documented before: instead of relying on discrete pulses of flow left by hopping copepods, this high alpine lake copepod followed smoothly swimming mates or continuously flowing thin streams, relying only on sensing hydrodynamic cues.

Orientadora: Maria Célia Portella
Banca: Irene Bastos Franceschini Vicentini
Banca: Marcos Antonio Cestarolli
Resumo: O pacu Piaractus mesopotamicus é uma das espécies de maior relevância na piscicultura de águas quentes no Brasil, destacando-se pela qualidade de sua carne e desempenho em sistemas de cultivo. Apesar do avanço no estudo da biologia, anatomia e morfologia da espécie, os aspectos relacionados com o desenvolvimento inicial do sistema sensorial são praticamente desconhecidos. Este estudo teve por objetivo descrever o desenvolvimento inicial de pacu Piaractus mesopotamicus, com ênfase na ontogenia das estruturas sensoriais. Para isto, amostras seriadas de embriões e larvas em desenvolvimento foram coletadas desde as 9 horas pós fertilização (hpf) até os 25 dias pós eclosão (dpe), e destinadas para análises morfológicas, histológicas e de microscopia eletrônica de varredura. O desenvolvimento embrionário da espécie é rápido, e cerca das 19 hpf(a 26,S ± O,SOC), as larvas eclodem num estado altricial (3,19 ± 0,04 mm comprimento notocordal- CN; 0,477 ± 0,061 mm3 volume do saco+ vitelino¬VSV). Na eclosão, o desenvolvimento do sistema sensorial é limitado: no epitélio olfatório observam-se neurônios sensoriais ciliados e neurônios sensoriais com microvilosidades; a presença de mecanorreceptores é restrita ao neuromasto ótico imaturo; o desenvolvimento do ouvido interno é incipiente, observa-se a presença de dois otólitos em cada cápsula ótica, mas a larva ainda não apresenta estabilidade na coluna de água nem coordenação nos seus movimentos; e os olhos apresentam-se com pouco ou nenhum pigmento, lente diferenciada e separada da córnea, e retina não estratificada No entanto, o desenvolvimento pós-embrionário do sistema sensorial é acelerado: a partir de 1 dpe o epitélio olfativo se encontra coberto por uma densa camada de cilios não sensoriais que se distribuem. tanto na vesícula...(Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Pacu, Piaractus mesopotamicus, is one of the species of major importance for warmwater fish farming in Brazil due to its meat quality and performance in culture systems. Despite the advances in the study of biology, anatomy and morphology of the species, the aspects related to the early development of the sensorial system are unknown. The aim of this study was to describe the initial development of pacu Piaractus mesopotamicus, with emphasis on the ontogeny of the sensorial structures. Embryos and larvae were serially sampled during development, from the 9 hours after fertilization (haf) to the 25 days after hatching (dah), and subjected to the morphology, histology and scanning electron microscopy analysis. The embryonic development of the species is fast: about 19 haf (at 26,5 ± 0,5°C), larvae hatch in an altricial state (3.19 ± 0.04 mm notochordal length - NL; 0.477 ± 0.061 mm3 yolk-sac volume - YSV). At hatching, the sensorial system development is limited: in the olfactory epithelium, there are ciliated sensorial neurons and microvillous sensorial neurons; the mechanoreceptors are restricted to the immature otic neuromast; the development of the inner ear is incipient, with two otoliths in each otic capsule, but larvae do not show neither stability in the water column or coordination of their movements; the eyes have no or few pigment, with lens differentiated and separated from the cornea, and non-stratified retina. However, the post-embryonic development of the sensorial system is accelerated: from the 1 st dah the olfactory epithelium is covered by a dense layer of non sensorial cilia, which are distributed in the olfactory vesicle and in the epithelium region around it; at 2,5-3 dah, the eyes are totally pigmented; from the 4th dah it is possible to identify solitary chemosensorial cells in the post-otical region;...(Complete abstract click electronic access below)
Mestre

Made available in DSpace on 2014-06-11T19:22:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-07-25Bitstream added on 2014-06-13T18:08:10Z : No. of bitstreams: 1 clavijoayala_ja_me_jabo_prot.pdf: 2110673 bytes, checksum: 81a603896afe42aa218b5fa3b86d612c (MD5)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O pacu Piaractus mesopotamicus é uma das espécies de maior relevância na piscicultura de águas quentes no Brasil, destacando-se pela qualidade de sua carne e desempenho em sistemas de cultivo. Apesar do avanço no estudo da biologia, anatomia e morfologia da espécie, os aspectos relacionados com o desenvolvimento inicial do sistema sensorial são praticamente desconhecidos. Este estudo teve por objetivo descrever o desenvolvimento inicial de pacu Piaractus mesopotamicus, com ênfase na ontogenia das estruturas sensoriais. Para isto, amostras seriadas de embriões e larvas em desenvolvimento foram coletadas desde as 9 horas pós fertilização (hpf) até os 25 dias pós eclosão (dpe), e destinadas para análises morfológicas, histológicas e de microscopia eletrônica de varredura. O desenvolvimento embrionário da espécie é rápido, e cerca das 19 hpf(a 26,S ± O,SOC), as larvas eclodem num estado altricial (3,19 ± 0,04 mm comprimento notocordal- CN; 0,477 ± 0,061 mm3 volume do saco+ vitelino¬VSV). Na eclosão, o desenvolvimento do sistema sensorial é limitado: no epitélio olfatório observam-se neurônios sensoriais ciliados e neurônios sensoriais com microvilosidades; a presença de mecanorreceptores é restrita ao neuromasto ótico imaturo; o desenvolvimento do ouvido interno é incipiente, observa-se a presença de dois otólitos em cada cápsula ótica, mas a larva ainda não apresenta estabilidade na coluna de água nem coordenação nos seus movimentos; e os olhos apresentam-se com pouco ou nenhum pigmento, lente diferenciada e separada da córnea, e retina não estratificada No entanto, o desenvolvimento pós-embrionário do sistema sensorial é acelerado: a partir de 1 dpe o epitélio olfativo se encontra coberto por uma densa camada de cilios não sensoriais que se distribuem. tanto na vesícula...
Pacu, Piaractus mesopotamicus, is one of the species of major importance for warmwater fish farming in Brazil due to its meat quality and performance in culture systems. Despite the advances in the study of biology, anatomy and morphology of the species, the aspects related to the early development of the sensorial system are unknown. The aim of this study was to describe the initial development of pacu Piaractus mesopotamicus, with emphasis on the ontogeny of the sensorial structures. Embryos and larvae were serially sampled during development, from the 9 hours after fertilization (haf) to the 25 days after hatching (dah), and subjected to the morphology, histology and scanning electron microscopy analysis. The embryonic development of the species is fast: about 19 haf (at 26,5 ± 0,5°C), larvae hatch in an altricial state (3.19 ± 0.04 mm notochordal length - NL; 0.477 ± 0.061 mm3 yolk-sac volume - YSV). At hatching, the sensorial system development is limited: in the olfactory epithelium, there are ciliated sensorial neurons and microvillous sensorial neurons; the mechanoreceptors are restricted to the immature otic neuromast; the development of the inner ear is incipient, with two otoliths in each otic capsule, but larvae do not show neither stability in the water column or coordination of their movements; the eyes have no or few pigment, with lens differentiated and separated from the cornea, and non-stratified retina. However, the post-embryonic development of the sensorial system is accelerated: from the 1 st dah the olfactory epithelium is covered by a dense layer of non sensorial cilia, which are distributed in the olfactory vesicle and in the epithelium region around it; at 2,5-3 dah, the eyes are totally pigmented; from the 4th dah it is possible to identify solitary chemosensorial cells in the post-otical region;...(Complete abstract click electronic access below)

Thesis (Ph.D.)--University of Florida, 2005.
Typescript. Title from title page of source document. Document formatted into pages; contains 124 pages. Includes Vita. Includes bibliographical references.

Endothelial cell (EC) function is affected by forces generated by flowing blood on the arterial wall (wall shear stress, WSS). Unidirectional WSS and laminar flow occurs in unbranched areas of the arteries, which are protected from atherosclerosis, whereas oscillatory WSS and “disturbed flow” occurs at branch points, where the majority of atherosclerotic plaques are initiated. EC can sense forces via multiple mechanoreceptors including β1- integrin, which induces downstream signalling in response to WSS. Although EC can distinguish between unidirectional and oscillatory WSS, the mechanisms that control this are unknown. We hypothesized that mechanoreceptors are activated by specific mechanical conditions which trigger downstream signalling, i.e. some mechanoreceptors are activated by unidirectional WSS whereas others are activated by bidirectional force. We examined the effect of flow direction and frequency of oscillation on calcium signalling and how the mechanical activation of β1- integrin contributes to these responses. We found significant differences in calcium dynamics in ECs exposed to different flow conditions. Using magnetic beads, unidirectional force but not bidirectional force applied directly to apical β1- integrin induced its conversion from a bent inactive to an extended active form. Furthermore, application of unidirectional force to β1- integrin induced calcium release from the inner stores of the endoplasmic reticulum. Finally, studies using pharmacological inhibitors revealed that phospholipase C and ROCK regulate the calcium responses triggered by mechanostimulation of β1- integrin. These results are consistent with the hypothesis that distinct endothelial mechanoreceptors respond to different flow patterns. My work suggests that β1- integrin functions as a mechanoreceptor that can distinguish between different force directions.

The therapeutic benefits attributed to activation of peripheral mechanoreceptors are poorly understood. There is growing evidence that mechanical stimulation modulates substrates in the supraspinal central nervous system (CNS) that are outside the canonical somatosensory circuits. This work demonstrates that activation of peripheral mechnoreceptors via mechanical stimulation (MStim) is sufficient to increase dopamine release in the nucleus accumbens (NAc), alter neuron firing rate in the ventral tegmental area (VTA) and increase membrane translocation of delta opioid receptors (DORs) in the NAc. Further, we demonstrate that these effects are dependent on DORs and acetylcholine receptors. Additionally, MStim can block neuronal markers of chronic ethanol dependence including ethanol-induced changes to VTA GABA neuron firing during withdrawal, and DA release profiles after reinstatement ethanol during withdrawal. These are presented in tandem with evidence that MStim also ameliorates behavioral indices of ethanol withdrawal. Finally, exercise, a modality that includes a mechanosensory component, is shown to alter expression of kappa opioid receptors (KORs) in the NAc. This change substantively depresses KORs influence over evoked DA release in direct contraversion to the effects of chronic ethanol. These changes translate into reduced drinking behavior.

Mechanotransduction is fundamental to many sensory processes, including balance, hearing and motor co-ordination. However, for such an essential feature, the mechanism(s) that underlie it are poorly understood. The mechanotransducing stretch receptors that relay information on the tonicity and length of skeletal muscles have been well-defined, particularly at the gross anatomical level, in a wide variety of species, encompassing both vertebrates and invertebrates. To date, there exists a wealth of data describing them, anatomically, as well as good electrophysiological data from stretch receptors of some larger organisms. However, comparatively few studies have succeeded in identifying putative mechanotransducing molecules in such systems. Nonetheless, this class of sensory mechanotransducers perhaps offer the best means of identifying molecules that permit the stretch-sensitivity of such endings, revealing new information about the underlying mechanisms of stretch receptors, and mechanoreceptors more generally. However, a different approach is clearly needed; a theoretical approach, utilising mathematical modelling, offers a powerful means of pooling the current wealth of knowledge on the reported electrophysiological behaviour of muscle stretch receptors. This study, therefore, develops an extended theoretical model of a stretch receptor system in order to reproduce, in silico, the reported behaviour of both vertebrate and invertebrate stretch receptors, within the same modelling environment, thus enabling the first quantitative framework for comparing these data, and moreover, making predictions of the likely roles of specific molecular entities within a stretch receptor system. Subsequently, this study utilises a model in vivo system to test these theoretical predictions. The genetic toolbox of D. melanogaster offers a wide range of tools that are extremely suitable for identifying mechanotransducing molecules in stretch receptors. However, very little is currently known about such endings in this organism. This study, therefore, firstly characterises a putative stretch receptor organ in larval Drosophila, the dbd neuron, via a novel experimental approach. It is shown that this neuron exhibits known properties of stretch receptors, as previously observed in other, similar organs. Furthermore, these observations bear out the predictions of the mathematical model. Having defined the dbd neuron as a muscle stretch receptor, pharmacological and genetic assays in this system, combined with predictions from the mathematical model, identify a key role for the recently-discovered DmPiezo protein as an amiloride-sensitive, mechanically-gated sodium channel (MNaC) in dbd neurons, with TRPA1 also acting in this system in a supporting role. These data confirm the essential role of an MNaC in mechanosensory systems, but also supply important evidence that, whilst the electrophysiological mechanisms in stretch receptors are remarkably similar across taxa, different species likely employ various molecular mechanisms to achieve this.

Somatosensory neurons are essential for detecting diverse environmental stimuli, thus critical for survival of mammals. In order to achieve sensory modality specificity, many somatosensory subtypes emerge with various receptor and ion channel expression, as well as terminal morphologies. How the somatosensory system achieves such a high variety of neuronal subtypes is unknown. In this thesis, I used a newly discovered subtype, VGLUT3-expressing unmyelinated low-threshold mechanoreceptors (C-LTMRs), as a model to try to answer this question. C-LTMRs have been proposed to play a role in pleasant touch in humans or pain in mice. Previously, our lab has identified the Runt domain transcriptional factor Runx1 to be pivotal for the development of a cohort of sensory neurons such as pain related nociceptors, thermal receptors, as well as itch related pruriceptors. Here I found that Runx1 is also required to establish all known features associated with C-LTMRs. In search of the mechanism of how Runx1 controls C-LTMR development, I found that the zinc finger protein Zfp521 is predominantly expressed in C-LTMRs and its expression is Runx1 dependent. By generating and analyzing Zfp521 conditional knock out animals, I found Zfp521 is required for part of C-LTMR molecular identities and nerve terminal morphologies. Our studies suggest that Runx1 acts through Zfp521-dependent and Zfp521-independent pathways to specify C-LTMR identities. To study C-LTMR functions, we performed a series of behavioral analysis and found the loss of VGLUT3 and mechanosensitivities in C-LTMRs does not markedly affect acute or chronic mechanical pain measured from the hind paws, which argues against the proposed role of VGLUT3 in C-LTMRs in mediating mechanical pain in mice. In the future, we will continue to use our mutant mice to study physiological functions of C-LTMRs.

Reflex effects evoked by graded electrical stimulation of the posterior articular nerves (PAN) of the ipsi- and contralateral knee joints were investigated using both micro-electrode recordings from 7 - motoneurones and recordings from single muscle muscle spindle afferents. Spindle afferent responses were also recorded using natural stimulation of different types of receptors, to elucidate if the articular reflexes onto the y -motoneurones were potent enough to significantly alter the muscle spindle afferent activity. Stretches of the ipsilateral posterior (PCL) and anterior (ACL) cruciate ligaments, pressure on the ipsi- and contralateral knee and ankle joint capsules, and passive flexion/extension movements of the joints in the contralateral hind limb were performed. The occurrance of different sensory endings in the ACL and PCL was examined using gold chloride staining for neuronal elements. All experiments were performed on chloralose anaesthetized cats. More than 90% of the static and dynamic y -motoneurones were responsive to electrical stimulation of the PAN. Most 7-cells responded to low intensity electrical stimulation. Excitatoiy reflex effects predominated on both static and dynamic posterior biceps-semitendinosus (PBSt) 7 -cells, while excitatory and inhibitory effects occurred with an about equal frequency on triceps-plantaris (GS) 7-cells. The fastest segmental route for excitatory PAN effects on hind limb 7-motoneurones seems to be di- or trisynaptic, while the path for inhibitory effects seems to be at least one synaps longer. Physiological stimulations of ipsi- and contralateral joint capsules and of ipsilateral cruciate ligaments were all found to evoke frequent and potent changes in spindle afferent responses from the GS and PBSt muscles. It was shown that these effects were due to reflexes onto dynamic and static fusimotor neurones caused by physiological activation of articular sensory endings. Both ipsi- and contralateral joint receptor stimulation evoked excitatory as well as inhibitory fusimotor effects. The highest responsiveness was found during stimula­tion of the cruciate ligaments, i.e. 58% for GS and 47% for PBSt primary spindle afferents to PCL stimula­tion, and 73% for GS and 55% for PBSt primary spindle afferents to ACL stimulation. Significant altera­tions in spindle afferent activity was encountered at very low traction forces applied to the cruciate ligaments (5-10 N). The low thresholds, the tonic character of the stimuli, and the fact that different types of sensory endings were demonstrated in the cruciate ligaments (i.e. Ruffini endings, Pacinian corpuscles, Golgi ten­don organ like endings and free nerve endings), indicate that the fusimotor effects observed were caused by activation of slowly adapting mechanoreceptors, most likely Ruffini endings and/or Golgi tendon organ like endings. The potent reflex effects on the muscle spindle afferents elicited by increased tension in the cruciate ligaments indicate that these ligaments may play a more important sensory role that hitherto believed, and it is suggested that they may be important in the regulation of the stiffness of muscles around the knee joint, and thereby for the joint stability. The possible clinical relevance and the mechanisms by which joint receptor afferents, via adjustment of the muscle stiffness, may control joint stability are discussed.

Diss. (sammanfattning) Umeå : Umeå universitet, 1989, härtill 7 uppsatser.

digitalisering@umu

Le système nerveux somatosensoriel permet l'interaction entre l'organisme et son environnement. Ce système collecte, via des récepteurs périphériques, les stimuli extérieurs et les transmet au système nerveux central par les neurones sensoriels primaires, dont les corps cellulaires sont situés dans les ganglions rachidiens dorsaux. Ces neurones primaires sont spécifiques des différentes sensations et ont, pour y répondre, des récepteurs, des modalités sensorielles, des caractéristiques moléculaires différentes. Ils sont généralement séparés en 3 grandes familles: les propriocepteurs, les mécanocepteurs et les nocicepteurs, chacune de ces familles se séparant à son tour en une multitude de sous familles. Ces neurones dérivent de la crête neurale, une structure spécifique des vertébrés. Au cours de leur migration vers les ganglions rachidiens dorsaux, les cellules vont être soumises à un grand nombre de facteurs et de voies de signalisation, qui vont entrainer leur survie, leur mort ou leur différenciation. Le facteur de transcription Meis2 a été isolé par l'équipe comme un candidat pouvant intervenir dans cette différentiation des cellules en neurones différenciés. Chez les souris, son expression est spécifique de sous populations mécanoceptives et proprioceptives, et s'étend des stades précoces de développement jusqu'à l'âge adulte. La lignée conditionnelle de souris Knock Out pour Meis2, croisée avec la lignée Wnt1cre, permet l'abolition de Meis2 dans toutes les cellules de la crête neurale et ses dérivés. Le mutant issu de ce croisement meurt à la naissance, avec de nombreux problèmes phénotypiques. Cette lignée cKOMeis2 a alors été croisée avec la lignée Islet1cre, ce qui permet d'invalider le gène Meis2 dans les neurones post-mitotiques des ganglions rachidiens dorsaux. Cette souris m'a servi de modèle afin de déterminer les conséquences éventuelles de la perte de Meis2 dans les neurones sensoriels du ganglion rachidien dorsal par analyse comportementale
The somatosensory nervous system allows the interaction between the organism and the environment. This system receives from peripheral receptors some exterior stimuli which are transmitted to the central nervous system by sensory primary neurons. Their cell bodies are located in the dorsal root ganglions (DRG). These primary neurons are specific to various sensations and are characterized by specific receptors, sensory modalities and molecular characteristics involved in their response. They are usually defined as belonging to one of three main families: proprioceptors, mecanoceptors and nociceptors, and each family is composed of a large number of subgroups. These neurons are derived from the neural crest cells to form the DRG. The cells are exposed to a number of key pathways and factors, which permit their survival, death or differentiation. The transcription factor Meis2 was isolated by our team as a good candidate to act in the differentiation or specification of these cells into sensory neurons. The expression pattern of Meis2 is shown to be specific to the mecanoceptor and proprioceptor subgroups and starts, in mice, from the early stages of development up to the adult age. To investigate the role of Meis2 the conditional strain mice Meis2 Knock Out (cKOMeis2) were crossed with the strain Wnt1cre which invalidates the gene Meis2 in all the neural crest and derived cells. The new born mice die at birth with most showing phenotypic dysfunctions. Finally, this cKOMeis2 strain was crossed with Islet1cre which specifically disrupts the Meis2 gene in post-mitotic DRG neurons. This thesis characterises the Islet1cre/+cKOMeis2LoxP/LoxP strain in order to determine the behavioural consequences of the loss of the Meis2 protein in DRG sensory neurons

Le traitement et la gestion de la douleur sont depuis toujours une priorité pour le corps médical. Malgré leur importance pour la qualité de vie, les analgésiques couramment utilisés possèdent un ratio bénéfice/risque faible. La recherche de nouveaux concepts thérapeutiques pour lutter contre la douleur est donc une priorité. Afin de répondre à ce besoin, il faut d'abord comprendre les mécanismes de la perception de la douleur ainsi que, plus globalement, ceux permettant de percevoir son environnement. Dans ce contexte, de nombreuses études ont mis en évidence l'implication du canal calcique à bas seuil Cav3.2 dans les voies de la transmission de l'information douloureuse. Il représente donc une cible de choix pour le traitement de la douleur mais l'identité des neurones exprimant ces canaux ainsi que la fonction de Cav3.2 dans la physiologie des neurones sensoriels étaient jusqu'à présent inconnues. Au cours de cette thèse nous avons dans un premier temps décrit un nouvel inhibiteur des canaux calciques à bas seuil : le TTA-A2. Nous avons ainsi démontré que le TTA-A2 est un inhibiteur spécifique des canaux Cav3.1, Cav3.2, et Cav3.3. Il permet de diminuer l'excitabilité des neurones sensoriels exprimant Cav3.2, ce qui provoque une analgésie sur des animaux sains et pathologiques. Dans un deuxième temps nous nous sommes servis de ce nouvel outil en parallèle d'un nouveau modèle murin possédant une étiquette fluorescente (Knock in GFP) sur le canal Cav3.2 pour explorer la localisation et la fonction de Cav3.2 dans les neurones sensoriels. Nous avons ainsi découvert que Cav3.2 est exprimé dans des mécanorécepteurs à bas seuil impliqués dans la perception des stimuli mécaniques et thermiques nocifs ou non-nocifs. Le canal en lui-même se trouve aux endroits clés de la genèse et de la propagation du message nerveux périphérique, et module le seuil et la vitesse de conduction des potentiels d'action. Replacé dans le contexte de la bibliographie, l'ensemble de nos résultats montre que Cav3.2 permet de donner la modalité à bas seuil aux neurones l'exprimant
Pain management and treatment have always been a priority for life quality. Despite this fact, analgesics commonly used present a bad benefice/risk ratio. Discovery of new therapeutic concepts to fight pain is highly required. To complete this task, we first need to better understand pain perception mechanisms, and more globally, mechanisms involved in the perception of our environment. In this context, numerous studies have shown that low threshold calcium channels Cav3.2 are involved in pain information transmission. Thus, it represents a good target for the treatment of pain. However, neuronal identity of Cav3.2-expressing sensory neurons and Cav3.2 functions in neuronal physiology are unknown. During this PhD we first described a new low voltage activated channel antagonist named TTA-A2. We demonstrated that TTA-A2 is a powerful nanomolar specific agonist of Cav3.1, Cav3.2 and Cav3.3. This molecule is able to reduce excitability in sensory neurons expressing Cav3.2, and is able to generate a strong analgesic effect on naive and pathologic animals. In the other part of this PhD, we used this new tool combined to a new transgenic mouse that expressed Cav3.2 tagged with a fluorescent protein (Knock-in GFP). With these new tools we discovered that Cav3.2 is expressed in low threshold mechanoreceptors involved in detection of painful and non painful mechanical and thermal stimuli. Cav3.2 itself is expressed at key localisations that allow action potential generation and propagation, and modulate threshold and speed conduction of action potential. Taken together, these results show that Cav3.2 gives the “low threshold” modality to neurons

Striped bass larvae, native to the Shubenacadie River, catch invertebrates in darkness using mechanoreception via lateral line neuromasts. The neuromast total increased from 17 at first feeding (5 to 7 dph) to 135 by the juvenile stage (27 dph). A 5 mM neomycin dose ablated neuromasts, confirmed by fluorescent and confocal microscopy. In feeding trials, larvae with and without functional neuromasts were offered Artemia salina in darkness or light. To identify ontogenetic changes in feeding, experiments were repeated at 10, 13, 17, and 20 dph. In darkness, neomycin treated larvae caught fewer prey (~5 Artemia h-1 at all ages, p<0.05) than larvae with intact neuromasts (10 dph, 16 Artemia h-1; 20 dph, 72 Artemia h-1). In light, neomycin did not affect feeding, indicating no deleterious side-effects. Neomycin did not damage olfactory or taste cells judged by FM1-43FX and calretinin staining. The results support the contribution of mechanoreception to non-visual feeding.
Master's thesis