Embryonic depletion of serotonin affects cortical development

Compelling evidence suggests that serotonin (5-HT) is necessary for the refined organization of the cerebral cortex. Here we sought to analyse the short- and long-term consequences of embryonic 5-HT depletion on the development of the cerebral neocortex of the rat. We focused on the migration and differentiation of the pyramidal (projection) and nonpyramidal (interneuron) neuronal populations. Our paradigm used daily injection of DL-P-chlorophenylalanine (PCPA), a reversible inhibitor of 5-HT synthesis, during the E12-17 stage of embryonic development, when major events in corticogenesis take place. We monitored the 5-HT depletion induced by this treatment and showed that it led to subtle alterations in both the pyramidal and nonpyramidal neuronal populations. We found that E12-17 PCPA treatment altered the maturation of pyramidal neurons of layers III and V of the somatosensory cortex, with these cells displaying reduced dendritic arborization and complexity. These long-lasting alterations were not associated with modification of cortical BDNF levels at postnatal stages. We also showed that PCPA treatment transiently altered the incorporation in the cortical plate of interneurons derived from the caudal ganglionic eminence, and persistently affected the differentiation of a subpopulation expressing calretinin and/or cholecystokinin.