Special relationship of gamma-aminobutyric acid to the ventromedial nucleus of the hypothalamus during embryonic development

The ventromedial nucleus of the hypothalamus (VMH) is a key nucleus for reg ulating homeostatic, neuroendocrine, and behavioral functions. We conducted immunocytochemical analyses by using antisera directed against gamma-amino butyric acid (GABA), its synthetic enzyme glutamic acid decarboxylase (GAD6 7), GABA-A receptor subunits (alpha 2, beta 3, epsilon), estrogen receptor- alpha, and Neuropeptide Y (NPY) in the region of the VMH. in embryonic mice to identify potential patterning elements for VMH formation. Cells and fib ers containing GABA and GAD67 encircled the primordial VMH as early as embr yonic day 13 (E13) when the cytoarchitecture of the VMH was not recognizabl e by Nissl stain. At E16-17 the cytoarchitecture of the VMH became recogniz able by Nissl stain as GABAergic fibers invaded the nucleus, continued post natally, and by adulthood the density of GABAergic fibers was greater insid e than outside the VMH. GABA-A receptor subunit expression (beta 3 by E13 a nd alpha 2 by E15) within the primordial VMH suggested potential sensitivit y to the surrounding GABA signal. Brain slices were used to test whether fi bers from distal or proximal sites influenced VMH development. Coronal Vibr atome slices were prepared and maintained in vitro for 0-3 days. Nissl stai n analyses showed a uniform distribution of cells in the region of the VMH on the day of plating (E15). After 3 days in vitro, cellular aggregation su ggesting VMH formation was seen. Nuclear formation in vitro suggests that k ey factors resided locally within the coronal plane of the slices. It is su ggested that either GABA intrinsic to the region nearby the VMH directly in fluences the development and organization of the VMH, or along with other m arkers provides an early indicator of pattern determination that precedes t he cellular organization of the VMH. (C) 1999 Wiley-Liss, Inc.