Résumé des résultats (Abstract)
(Anglais)
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The wide range of effects of the neurotransmitter serotonin are mediated by numerous receptor types and transporter expressed in discrete brain regions and periods of life. Combining observations made in the whole brain of knock-out animals and in tissue culture, we provide evidence for two mechanisms in cerebral cortex development modulated by serotonin. First of all, the migration rate of neuronal precursors from their site of generation to their final location in the cortex is promoted by increased levels of serotonin. Two lines of evidence support this statement: In vitro, the proportion of neurons reaching the destination in the superficial layers is significantly increased in slices maintained in a medium supplemented with serotonin, as compared to serotonin-free medium. In vivo: the rate of migration of neuroblasts reaching their target in the cortical plate is advanced in animals with transiently elevated extracellular content. Both observations are consistent with the concept that serotonin stimulate the process of radial migration of the neuroblasts. Secondly, the growth and branching of dendrites arising from a specific population of cortical interneurons is modulated by a specific serotonin receptor and second messenger pathways. Following previous observations on the modification of the dendritic phenotype of these neurons in response to serotonin or nitric oxyd (a second messenger pathway associated with 5-HT2 receptors), the putative involvement of cGMP as candidate downstream effector was supported by the observations that an inhibitor of this enzyme antagonized the 5-HT2A receptor and an activator of this enzyme mimicked the effect of 5-HT in serotonin-free medium. These two processes are critical for proper connectivity, and hence functioning, in the cerebral cortex. Finally, the transient expression of serotonin and monoamine transporters, shown in rodent models to affect the segregation of several sensory afferent pathways, has been demonstrated in the primate brain. It is present in several sensory afferent pathways including retinogeniculate and retinotectal projections, in olfactory nerves, cranial and spinal sensory ganglia, and several sensory brainstem nuclei. However, it was missing in the thalamocortical projection, at variance to the observation in rodent brains.This developmental process is likely to be operating in primates as in rodents, but may not be preserved in all the same projections. This might be a source of adverse effects of the use of transporter blockers as medication or drug of abuse during the pregnancy.
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