Seules deux structures du système nerveux central adulte, la zone sous-granulaire et la zone sous-ventriculaire, produisent continuellement de nouveaux neurones et sont considérées comme neurogènes. En dehors de ces zones délimitées, le tissu nerveux ne possède pas de telles facultés. Leurs influences anti-neurogènes peuvent cependant être mises entre parenthèses dans certaines conditions. Cela se produit après neurectomie vestibulaire unilatérale (NVU) chez le chat adulte ; en effet, des études immunohistochimiques et comportementales nous ont permis de découvrir l'existence d'une neurogenèse réactionnelle de type GABAergique dans les noyaux vestibulaires désafférentés situés dans le tronc cérébral. Nos résultats témoignent de l'implication fonctionnelle de cette prolifération cellulaire dans la restauration des fonctions posturo-locomotrices suite à une NVU. Nous avons également mis en évidence que les caractéristiques et l'intensité de la désafférentation vestibulaire déterminent, non seulement, le décours temporel de la restauration des fonctions vestibulaires, mais aussi les différents mécanismes cellulaires post-lésionnels et le potentiel neurogène des noyaux vestibulaires. En outre, nous avons démontré que l'activation ou le blocage des récepteurs GABA de type A influence d'une part, les différentes étapes de la neurogenèse réactionnelle dans les noyaux vestibulaires, et détermine d'autre part le décours de la récupération comportementale des animaux. Ainsi, le système GABAergique joue-t-il un rôle important dans la régulation de la neurogenèse induite après NVU et de sa fonctionnalité. / Only two structures of the adult central nervous system: the subgranular zone and the subventricular zone, produce continuously new neurons and are considered as neurogenic. Outside these two delimited areas, nervous tissue does not have such faculties. The anti-neurogenic influences can however be removed under specific conditions. That is what happens after unilateral vestibular neurectomy (UVN) in the adult cat: behavioral and immunohistochemical studies have demonstrated the existence of a reactive GABAergic neurogenesis in the deafferented vestibular nuclei located in the brainstem. Our results demonstrate the functional role of the vestibular cell proliferation in the postural locomotor function recovery after UVN. We also demonstrated that characteristics and intensity of the vestibular lesion, not only determine the time course of recovery of vestibular function, but also the post-lesional cellular mechanisms and the neurogenic potential occurring in the vestibular nuclei. In addition, we showed that activation or blockade of GABA type A receptors influences the different steps of neurogenesis in the vestibular nuclei, and also determines the time course of behavioral recovery. Thus, the GABAergic system influences reactive neurogenesis that is benefic for vestibular compensation process. Finally, the results of a recent study demonstrated that vestibular-hippocampal relations exist, and that stress induced by vestibular deafferentation can modulate adult neurogenesis in both the vestibular nuclei and the dentate gyrus in the adult cat.

No / The ability of neurons to modulate synaptic strength underpins synaptic plasticity, learning and memory, and adaptation to sensory experience. Despite the importance of synaptic adaptation in directing, reinforcing, and revising the behavioral response to environmental influences, the cellular and molecular mechanisms underlying synaptic adaptation are far from clear. Brain-derived neurotrophic factor (BDNF) is a prime initiator of structural and functional synaptic adaptation. However, the signaling cascade activated by BDNF to initiate these adaptive changes has not been elucidated. We have previously shown that BDNF activates mitogen- and stress-activated kinase 1 (MSK1), which regulates gene transcription via the phosphorylation of both CREB and histone H3. Using mice with a kinase-dead knock-in mutation of MSK1, we now show that MSK1 is necessary for the upregulation of synaptic strength in response to environmental enrichment in vivo. Furthermore, neurons from MSK1 kinase-dead mice failed to show scaling of synaptic transmission in response to activity deprivation in vitro, a deficit that could be rescued by reintroduction of wild-type MSK1. We also show that MSK1 forms part of a BDNF- and MAPK-dependent signaling cascade required for homeostatic synaptic scaling, which likely resides in the ability of MSK1 to regulate cell surface GluA1 expression via the induction of Arc/Arg3.1. These results demonstrate that MSK1 is an integral part of a signaling pathway that underlies the adaptive response to synaptic and environmental experience. MSK1 may thus act as a key homeostat in the activity- and experience-dependent regulation of synaptic strength.