GABA promotes survival but not proliferation of parvalbumin-immunoreactiveinterneurons in rodent neostriatum: An in vivo study with stereology

Amino-acid neurotransmitters regulate a wide variety of developmental proce sses in the mammalian CNS including neurogenesis. cell migration, and apopt osis. In order to investigate the role of GABA in early development of Fore brain interneurons, we determined the survival of parvalbumin-immunoreactiv e GABAergic interneurons in the adult rat striatum following prenatal expos ure to either GABA(A) receptor agonist or antagonist. Unbiased stereology w as used to quantify parvalbumin-immunoreactive neuron number in the neostri atum of adult rats exposed to the drugs in utero. and the results were comp ared to pair-fed or vehicle controls. Embryos were exposed to the GABA(A) a ntagonist (bicuculline) or agonist (muscimol) during previously defined pro liferative or post-proliferative: periods for parvalbumin-immunoreactive in terneurons. Unbiased stereology using the optical fractionator was used to estimate the total number of parvalbumin-immunoreactive neurons in neostria tum of experimental and control rats. No significant alteration in parvalbu min-immunoreactive neuron number was observed in rats treated with either b icuculline (1 or 2 mg/kg/day) or muscimol (1 mg/kg/day) during the prolifer ative phase. Administration of bicuculline during the post-proliferative ph ase significantly reduced parvalbumin-immunoreactive neuron number in the n eostriatum. 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 distrib ution gradients for parvalbumin-immunoreactive neurons in neostriatum of ra ts exposed to bicuculline in the embryonic post-proliferative phase. This data collectively suggests that GABA promotes survival but not prolife ration of parvalbumin-immunoreactive progenitors. GABA may also promote mig ration of subpopulations of interneurons that ultimately populate the ventr al telencephalon. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rig hts reserved.