Glycine is one of the main inhibitory neurotransmitter in the central nervous system of vertebrates where it acts by activating a chloride conductance. The distribution of glycine receptor at the neuronal surface was analysed by immunocytochemistry with monoclonal antibodies raised against the purified receptor. In the rat spinal cord as well as in other areas of the central nervous system, these receptors are localized at the postsynaptic membrane and are concentrated in front of the presynaptic release sites. Thus, they define functional microdomains at the plasma membrane. A similar organisation was observed in a motor command neuron: the Mauthner cell of Teleosts. Further, in this model, a quantitative analysis using confocal microscopy has established that the postsynaptic microdomains are arranged according to a somatodendritic gradient with the larger clusters at the tip of the dendrites. The use of primary cultures of rat or mouse spinal cord neurons has allowed to study the ontogenesis of the glycine receptor. We have shown that these receptors are, here also, organized in clusters present at the neuronal surface and that the formation of these aggregates occurs simultaneously to the establishment of synaptic contacts.
Abstract The proper maturation of emotional and sensory circuits requires a fine tuning of serotonin (5-HT) level during early postnatal development. Consistently, dysfunctions of the serotonergic system have been associated with neurodevelopmental psychiatric diseases, including autism spectrum disorders (ASD). However, the mechanisms underlying the developmental effects of 5-HT remain partially unknown, one obstacle being the action of 5-HT on different cell types. Here, we focused on microglia, which play a role in brain wiring refinement, and we investigated whether the control of these cells by 5-HT is relevant for neurodevelopment and spontaneous behaviors. Since the main 5-HT sensor in microglia is the 5-HT 2B receptor subtype, we prevented 5-HT signaling specifically in microglia by conditionally invalidating Htr2b gene in these cells. We observed that abrogating the serotonergic control of microglia during postnatal development impacts the phagolysosomal compartment of these cells and their proximity to dendritic spines, and perturbs neuronal circuits maturation. Furthermore, this early ablation of microglial 5-HT 2B receptors leads to adult hyperactivity in a novel environment and behavioral defects in sociability and flexibility. Importantly, we show that these behavioral alterations result from a developmental effect, since they are not observed when microglial Htr2b invalidation is induced later, at P30 onward. Thus, a primary alteration of 5-HT sensing in microglia, during a critical time window between birth and P30, is sufficient to impair social and flexibility skills. This link between 5-HT and microglia may explain the association between serotonergic dysfunctions and behavioral traits like impaired sociability and inadaptability to novelty, which are prominent in psychiatric disorders such as ASD.
Le retrovirus aviaire mh2 induit la multiplication et la transformation des cellules de neuroretine (nr) d'embryons de poulet qui normalement ne se divisent pas. Le genome du virus mh2 contient deux oncogenes: v-mil et v-myc. L'isolement de mutants de mh2, deletes dans v-mil ou v-myc, nous a permis de preciser les proprietes biologiques de chacun des oncogenes et d'analyser les relations entre l'induction de la division cellulaire et la transformation. Le gene v-mil est responsable de la division des cellules de nr. Par contre, il induit un phenotype de transformation reduit dans les cellules infectees. La transformation des cellules de nr par mh2 necessite, donc, l'expression des deux oncogenes v-mil et v-myc. Le gene v-myc n'a pas d'effet mitogene ni transformant dans les cellules de nr quiescentes. Par contre, ce gene peut transformer des cellules de nr dont la division a ete induite soit par des oncogenes viraux, tels que v-src ou v-mil, soit par l'utilisation de milieux enrichis. L'expression des proprietes transformantes de v-myc dans les cellules de nr depend donc de leur etat de division. Les cellules de nr peuvent egalement etre induites a se diviser apres infection par un retrovirus depourvu d'oncogenes: le rav-1. Cette proliferation resulte, dans certains cas, de l'activation et de la transduction du gene cellulaire c-mil
