Journal
NEUROSCIENCE
Volume 151, Issue 4, Pages 1119-1131Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2007.11.048
Keywords
hypothalamic development; migration; GABA(B); receptors; estrogen receptors; arcuate nucleus
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Funding
- NICHD NIH HHS [HD07031-29, T32 HD007031] Funding Source: Medline
- NIMH NIH HHS [R01 MH057748, MH57748, R01 MH061376, R01 MH061376-06, MH61376] Funding Source: Medline
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The ventromedial (VMN) and arcuate (ARC) nuclei of the hypothalamus are bilateral nuclear groups at the base of the hypothalamus that are organized through the aggregation of neurons born along the third ventricle that migrate laterally. During development, GABAergic neurons and fibers surround the forming (or primordial) VMN while neurons containing GABA receptors are found within the boundaries of the emerging nucleus. To investigate the role that GABA(B) receptors play in establishing the VMN, Thy-1 yellow fluorescent protein (YFP) mice were utilized for live video microscopy studies. The Thy-1 promoter drives YFP expression in regions of the hypothalamus during development. Administration of the GABAB receptor antagonist saclofen and the GABA(A) receptor antagonist bicuculline selectively increased the rate of VMN cell movement in slices placed in vitro at embryonic day 14, when cells that form both the ARC and VMN are migrating away from the proliferative zone surrounding the third ventricle. To further test the role of GABAB receptors in VMN development, GABAB receptor knockout mice were used to examine changes in the positions of phenotypically identified cells within the VMN. Cells containing immunoreactive estrogen receptors (ER) a were located in the ventrolateral quadrant of the wild type VMN. In GABA(B)R1 knockout mice, these ER alpha positive neurons were located in more dorsal positions at postnatal day (P) 0 and P4. We conclude that GABA alters cell migration and its effect on final cell positioning may lead to changes in the circuitry and connections within specific nuclei of the developing hypothalamus. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
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