γ-Aminobutyric acid-mediated regulation of the activity-dependent olfactory bulb dopaminergic phenotype

✍ Scribed by Yosuke Akiba; Hayato Sasaki; Patricio T. Huerta; Alvaro G. Estevez; Harriet Baker; John W. Cave

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 478 KB
• Volume: 87
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.22055

✦ Synopsis

Abstract

γ‐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 (__Th__GFP). KCl‐mediated depolarization of the slices induced __Th__GFP expression. The addition of GABA to the depolarized slices further increased GFP fluorescence by inducing __Th__GFP 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 __Th__GFP expression required activation of L‐ and P/Q‐type Ca^2+^ channels as well as GABA~A~ and GABA~B~ receptors. These voltage‐gated Ca^2+^ 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. © 2009 Wiley‐Liss, Inc.