Dopamine affects parvalbumin expression during cortical development in vitro

This study was undertaken to determine how dopamine influences cortical dev elopment. It focused on morphogenesis of GABAergic neurons that contained t he calcium-binding protein parvalbumin (PV). Organotypic slices of frontopa rietal cortex were taken from neonatal rats, cultured with or without dopam ine, harvested daily (4-30 d), and immunostained for parvalbumin. Expressio n of parvalbumin occurred in the same regional and laminar sequence as in v ivo. Expression in cingulate and entorhinal preceded that in lateral fronto parietal cortices. Laminar expression progressed from layer V to VI and fin ally II-IV. Somal labeling preceded fiber labeling by 2 d. Dopamine accelerated PV expression. In treated slices, a dense band of PV-i mmunoreactive neurons appeared in layer V at 7 d in vitro (DIV), and in all layers of frontoparietal cortex at 14 DIV, whereas in control slices such labeling did not appear until 14 and 21 DIV, respectively. The laminar dist ribution and dendritic branching of PV-immunoreactive neurons were quantifi ed. More labeled neurons were in the superficial layers, and their dendriti c arborizations were significantly increased by dopamine. Treatment with a D1 receptor agonist had little effect, whereas a D2 agonist mimicked dopami ne's effects. Likewise, the D2 but not the D1 antagonist blocked dopamine-i nduced changes, indicating that they were mediated primarily by D2 receptor s. Parvalbumin expression was accelerated by dopaminergic reinnervation of cor tical slices that were cocultured with mesencephalic slices. Coapplication of the glutamate NMDA receptor antagonist MK801 or AP5 blocke d dopamine-induced increases in dendritic branching, suggesting that change s were mediated partly by interaction with glutamate to alter cortical exci tability.