GABA influences the development of the ventromedial nucleus of the hypothalamus

The region that becomes the ventromedial nucleus of the hypothalamus (VMH) is surrounded by cells and fibers containing immunoreactive gamma-aminobuty ric acid (GABA) by embryonic day 13 (E13), several days before the nucleus emerges in Nissl stains. As GABA plays many roles during neural development , we hypothesized that it influences VMH development, perhaps by providing boundary information for migrating neurons. To test this hypothesis we exam ined the VMH in embryonic mice in which the beta3 subunit of the GABA(A)-re ceptor, a receptor subunit that is normally highly expressed in this nucleu s, was disrupted by gene targeting. In beta3 -/- embryos the VMH was signif icantly larger, and the distribution of cells containing immunoreactive est rogen receptor-a was expanded compared to controls. Using in vitro brain sl ices from wild-type C57BL/6J mice killed at E15 we found that treatment wit h the GABA(A) antagonist bicuculline increased the number of cells migratin g per video field analyzed in the VMH. In addition, treatment with either b icuculline or the GABA(A) agonist muscimol altered the orientation of cell migration in particular regions of this nucleus. These data suggest that GA BA is important for the organization of cells during VMH formation. (C) 200 1 John Wiley & Sons, Inc.