GABA promotes survival but not proliferation of parvalbumin-immunoreactive interneurons in rodent neostriatum: an in vivo study with stereology.

Amino-acid neurotransmitters regulate a wide variety of developmental processes in the mammalian CNS including neurogenesis, cell migration, and apoptosis. In order to investigate the role of GABA in early development of forebrain interneurons, we determined the survival of parvalbumin-immunoreactive GABAergic interneurons in the adult rat striatum following prenatal exposure to either GABA(A) receptor agonist or antagonist. Unbiased stereology was used to quantify parvalbumin-immunoreactive neuron number in the neostriatum of adult rats exposed to the drugs in utero, and the results were compared to pair-fed or vehicle controls. Embryos were exposed to the GABA(A) antagonist (bicuculline) or agonist (muscimol) during previously defined proliferative or post-proliferative periods for parvalbumin-immunoreactive interneurons. Unbiased stereology using the optical fractionator was used to estimate the total number of parvalbumin-immunoreactive neurons in neostriatum of experimental and control rats. No significant alteration in parvalbumin-immunoreactive neuron number was observed in rats treated with either bicuculline (1 or 2mg/kg/day) or muscimol (1mg/kg/day) during the proliferative phase. Administration of bicuculline during the post-proliferative phase significantly reduced parvalbumin-immunoreactive neuron number in the neostriatum. A concomitant decrease in neostriatal volume was also observed, suggesting that the effect is not restricted to parvalbumin-immunoreactive interneurons. Positional analysis revealed loss of normal regional distribution gradients for parvalbumin-immunoreactive neurons in neostriatum of rats exposed to bicuculline in the embryonic post-proliferative phase. This data collectively suggests that GABA promotes survival but not proliferation of parvalbumin-immunoreactive progenitors. GABA may also promote migration of subpopulations of interneurons that ultimately populate the ventral telencephalon.