Elsevier

Neuroscience

Volume 123, Issue 3, 2004, Pages 793-803
Neuroscience

Neurons in the principal nucleus of the bed nuclei of the stria terminalis provide a sexually dimorphic gabaergic input to the anteroventral periventricular nucleus of the hypothalamus

https://doi.org/10.1016/j.neuroscience.2003.09.034Get rights and content

Abstract

Neurons of the principal nucleus of the bed nuclei of the stria terminalis (BSTp) process pheromonal and viscerosensory stimuli associated with reproduction and relay this information to preoptic and hypothalamic cell groups that regulate reproductive function. The anteroventral periventricular nucleus of the hypothalamus (AVPV), a nucleus involved in the regulation of gonadotropin secretory patterns, receives dense projections from BSTp neurons in males but not in females. By injecting the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHAL), into the BSTp of rats and immunohistochemically colocalizing the GABA synthetic enzyme, GAD65, to PHAL-immunoreactive fibers in the AVPV, we tested the hypothesis that these sex-specific projections arise from BSTp neurons that synthesize the inhibitory neurotransmitter GABA. Although dense GAD65-immunoreactive fiber terminals were observed in both the male and female AVPV, higher numbers of GAD65-labeled terminals were found in the male, and those localized to PHAL-immunoreactive fibers were seen almost exclusively in males. Treatment of newborn females with testosterone or neonatal orchidectomy of males reversed these sex differences, while GAD65-immunoreactivity in the AVPV was not altered in response to exogenous hormone treatments administered to peripubertal animals. Our results suggest that projections from BSTp neurons constitute a stable, sex-specific GABAergic input to the AVPV that is patterned permanently by perinatal hormone exposure.

Section snippets

PHAL injections

Experimental animals were adult (60–90 days of age) and peripubertal (21 days of age) male and female Sprague–Dawley rats (B & K Universal, Inc., Kent, WA, USA) housed on a 14/10 h light/dark cycle (lights on at 05:00 h), with food and water available ad libitum. All experimental procedures were approved by the Oregon Regional Primate Research Center Institutional Committee for the Care and Use of Animals in Research and Education, in accordance with the guidelines of the National Institutes of

Results

Three animals from each group of adult rats (MALE, FEMALE, FAS, GNX) and three to four peripubertal rats from each treatment group (MALE+T, MALE−T, FEMALE+E, FEMALE−E), all with comparably sized PHAL injections centered in the BSTp, were selected for analysis of fiber densities and numbers of GAD65-IR puncta (Fig. 1, top). The overall distributions of PHAL-labeled fibers in these cases were similar to those reported previously for peripubertal and adult rats (Gu et al., 2003, Hutton et al.,

Discussion

The present studies demonstrate the existence of a sexually dimorphic GABAergic projection from the BSTp to the AVPV. We have shown previously that projections from the BSTp to the AVPV are differentiated during development, resulting in a stable ‘male-typical’ or ‘female-typical’ phenotype (Gu et al., 2003, Hutton et al., 1998, Polston and Simerly, 2003). Here, we confirm the sex difference in the density of the projections from the BSTp to the AVPV and expand those findings, demonstrating

Acknowledgements

We thank Dr. Ake Lernmark and Dr. Paul Sawchenko for their generosity in providing us with the antisera against GAD65 (produced while under the support of NIH grant DK26190) and PHAL, respectively. We also wish to acknowledge the contributions of Dr. Anda Cornea for her expertise and advice pertaining to the confocal microscopy and image analysis procedures, and Jamie Colman for her assistance with perfusions and tissue processing. Supported by NIH NS37952 and RR00163 to R.B.S.

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