title: Earliest spontaneous activity differentially regulates neocortical GABAergic interneuron subpopulations.
abstract: Although less than one quarter of all neurons in the cerebral cortex are GABAergic, these neurons are morphologically diverse and their physiological complexity decisively moulds the network physiology. An important question is how different subpopulations of GABAergic neurons are regulated numerically during development. In rat neocortical cultures, neuronal precursors continue to divide, generating both GABAergic and non-GABAergic neurons. In vitro generated GABAergic neurons form a population of uniquely small, mostly fusiform neurons that differ in size and morphology from older, in situ generated, large stellate GABAergic neurons. In a large series of experiments we investigated the impact of neuronal activity on the development of these two subpopulations of GABA interneurons present in cortical networks during the first 2 weeks in vitro. Here we show that a moderate increase in the generation of GABAergic neurons was achieved by blocking activity with tetrodotoxin, indicating that intrinsic spontaneous activity inhibits GABAergic neurogenesis in culture. Antagonists to ionotropic glutamate receptor and/or GABA(A) receptor did not significantly alter GABAergic generation but agonists to these receptors showed a time-sensitive regulation of the size of small and large GABAergic neuronal subpopulations. Further, our results indicate that alterations of cell generation by activity manipulations might be overwritten by later activity effects on the survival of GABAergic cell populations.
authors.affiliation: Otto-von-Guericke University, Department of Developmental Physiology, Institute of Physiology, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
authors.forename: Ana D
authors.initials: AD
authors.lastname: de Lima
authors.forename: Beatriz D
authors.initials: BD
authors.lastname: Lima
authors.forename: Thomas
authors.initials: T
authors.lastname: Voigt
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007395:Interneurons / Q000145:classification / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D014404:Tubulin; D009118:Muscimol; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D001973:Bromodeoxyuridine; D007608:Kainic Acid