Projections of the sexually dimorphic calcitonin gene-related peptide neurons of the preoptic area determined by retrograde tracing in the female rat.

Abstract

The medial preoptic area of the rat exhibits morphologic sex differences and is implicated in the control of sexually dimorphic behavior and function. Neurons expressing calcitonin gene-related peptide (CGRP) within the anteroventral periventricular (AVPV) and medial preoptic nucleus (MPN) of the medial preoptic area exhibit female-dominant sex differences in number through organizational and activational effects of gonadal steroids. The present study used retrograde tracing experiments to establish the projections of the AVPV and MPN CGRP neurons in the female rat. After the intraperitoneal administration of Fluoro-Gold to female rats (n = 5), we were unable to detect retrograde tracer in any CGRP-immunoreactive cells of the hypothalamus. Intracerebral injections of 50- to 100-nl volumes of Fluoro-Gold into the mediobasal hypothalamus resulted in up to 70% of CGRP neurons in the AVPV and MPN containing retrograde tracer. Similar large volume tracer depositions in the lateral septum, periaqueductal gray, two likely CGRP projection sites, resulted in no labeling of preoptic CGRP neurons. Experiments using small volume (30-nl) injections of Fluoro-Gold and green fluorescent microspheres at multiple sites in the mediobasal hypothalamus (n = 18) revealed that approximately 60% of AVPV and 30% of MPN neurons expressing CGRP were projecting to the region of the tuberal and ventral premammillary nuclei, with a minor projection to the dorsomedial nucleus. These findings demonstrate a major projection of the preoptic CGRP neurons to the posterior hypothalamus in the female rat and support further a functional role for these neurons in the sexually dimorphic regulation of reproductive functioning.