title: gamma-Aminobutyric acid-mediated regulation of the activity-dependent olfactory bulb dopaminergic phenotype.
abstract: gamma-Aminobutyric acid (GABA) regulates the proliferation and migration of olfactory bulb (OB) interneuron progenitors derived from the subventricular zone (SVZ), but the role of GABA in the differentiation of these progenitors has been largely unexplored. This study examines the role of GABA in the differentiation of OB dopaminergic interneurons using neonatal forebrain organotypic slice cultures prepared from transgenic mice expressing green fluorescent protein (GFP) under the control of the tyrosine hydroxylase (Th) gene promoter (ThGFP). KCl-mediated depolarization of the slices induced ThGFP expression. The addition of GABA to the depolarized slices further increased GFP fluorescence by inducing ThGFP expression in an additional set of periglomerular cells. These findings show that GABA promoted differentiation of SVZ-derived OB dopaminergic interneurons and suggest that GABA indirectly regulated Th expression and OB dopaminergic neuron differentiation through an acceleration of the maturation rate for the dopaminergic progenitors. Additional studies revealed that the effect of GABA on ThGFP expression required activation of L- and P/Q-type Ca2+ channels as well as GABA(A) and GABA(B) receptors. These voltage-gated Ca2+ channels and GABA receptors have previously been shown to be required for the coexpressed GABAergic phenotype in the OB interneurons. Together, these findings suggest that Th expression and the differentiation of OB dopaminergic interneurons are coupled to the coexpressed GABAergic phenotype and demonstrate a novel role for GABA in neurogenesis.
authors.affiliation: Burke Medical Research Institute, White Plains, NY 10605. USA.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Akiba
authors.forename: Hayato
authors.initials: H
authors.lastname: Sasaki
authors.forename: Patricio T
authors.initials: PT
authors.lastname: Huerta
authors.forename: Alvaro G
authors.initials: AG
authors.lastname: Estevez
authors.forename: Harriet
authors.initials: H
authors.lastname: Baker
authors.forename: John W
authors.initials: JW
authors.lastname: Cave
mesh_terms: D060848:Agatoxins; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D009830:Olfactory Bulb / Q000166:cytology*; D010721:Phosphinic Acids / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D014966:Xanthenes / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D060848:Agatoxins; D000596:Amino Acids; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; C114624:LY 341495; D010721:Phosphinic Acids; D013111:Spider Venoms; D014966:Xanthenes; C060465:omega-agatoxin I; C086109:3-aminopropyl-cyclohexylmethylphosphinic acid; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D001640:Bicuculline