Site of origin of and sex differences in the vasopressin innervation of the mouse (Mus musculus) brain

Abstract

Defining how arginine vasopressin (AVP) acts centrally to regulate homeostasis and behavior is problematic, as AVP is made in multiple nuclei in the hypothalamus (i.e., paraventricular [PVN], supraoptic [SON], and suprachiasmatic [SCN]) and extended amygdala (i.e., bed nucleus of the stria terminalis [BNST] and medial amygdala [MeA]), and these groups of neurons have extensive projections throughout the brain. To understand the function of AVP, it is essential to know the site of origin of various projections. In mice, we used gonadectomy to eliminate gonadal steroid hormone-dependent expression of AVP in the BNST and MeA and electrolytic lesions to eliminate the SCN, effectively eliminating those AVP-immunoreactive projections; we also quantified AVP-immunoreactive fiber density in gonadectomized and sham-operated male and female mice to examine sex differences in AVP innervation. Our results suggest that the BNST/MeA AVP system innervates regions containing major modulatory neurotransmitters (e.g., serotonin and dopamine) and thus may be involved in regulating behavioral state. Furthermore, this system may be biased toward the regulation of male behavior, given the numerous regions in which males have a denser AVP-immunoreactive innervation than females. AVP from the SCN is found in regions important for the regulation of hormone output and behavior. Innervation from the PVN and SON is found in brain regions that likely work in concert with the well-known peripheral AVP actions of controlling homeostasis and stress response; female-biased sex differences in this system may be related to the heightened stress response observed in females.

Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

“…Specificity of the rabbit anti-Fos antibody was verified previously in rat brain tissue by lack of staining following preabsorption with either the Fos antigen (15) or the synthetic peptide immunogen (51). Guinea pig anti-AVP specificity was confirmed previously in mouse brain by preabsorption experiments using (Arg8)-AVP (47). The specificity of CTB antibody was confirmed by distribution of staining in regions of the PVN with known projections to the spinal cord and an absence of staining in other forebrain regions.…”

Developmental Perspectives on Oxytocin and Vasopressin

“…Oxytocin and vasopressin are both produced in the PVN and the supraoptic nucleus (SON) of the hypothalamus, while only vasopressin is produced in the suprachiasmatic nucleus, which emerges slightly later with a day-night rhythm of vasopressin content by E21 in rats (Reppert and Uhl, 1987). The rat extrahypothalamic vasopressin system (vasopressinproducing cells in the bed nucleus of the stria terminalis and the medial amygdala) is established early postnatally and is sexually dimorphic with much greater vasopressin production in males (De Vries et al, 1981;Szot and Dorsa, 1993;Rood et al, 2013). Sex differences in extrahypothalamic vasopressin production, which emerge by postnatal day 12 in rats, are testosterone dependent, leading to more immunoreactive fibers in the lateral septum and habenula (De Vries et al, 1981).…”

“…Compared with fibers in adult rats, fibers in the adult mouse appear to be even more widespread (Rood and De Vries, 2011), although a complete developmental profile in mice has not yet been performed for vasopressin immunoreactivity. Sex differences are apparent in adult mice too (Rood et al, 2013). Vasopressin development has been studied in golden hamsters (Delville et al, 1994b), and while male hamsters produce more vasopressin than female hamsters, the sex differences in hamsters are evident in the hypothalamus, and not the extrahypothalamic areas (Delville et al, 1994a).…”

Hypothalamic oxytocin and vasopressin neurons exert sex-specific effects on pair bonding, gregariousness, and aggression in finches

“…To date, experiments in voles have focused most extensively on nonapeptide receptors in the nucleus accumbens, ventral pallidum, and lateral septum (LS) (27). These brain regions receive direct input from several cell groups, including the SON, PVN, and medial extended amygdala (including the BSTm) (29,30), yet it is unclear which of these cell groups are relevant to pair bonding, and whether paracrine modulation from other cell groups plays a role.…”

“…In rodents, the LS receives direct innervation from VP neurons in the BSTm and OT neurons in the PVN (although light) (32), in addition to apparent paracrine modulation from VP-OT neurons in the SON and PVN (4)(5)(6). VP neurons in the suprachiasmatic nucleus also project heavily to areas that border the ventral LS and may therefore exert paracrine effects (29).…”