Estrogen‐induced dendritic spine elimination on female rat ventromedial hypothalamic neurons that project to the periaqueductal gray

Abstract

Neurons of the ventromedial hypothalamic nucleus (VMH) that project to the periaqueductal gray (PAG) form a crucial segment of the motor pathway that produces the lordosis posture, the hallmark of female rat sexual behavior. One suggested mechanism through which estrogen facilitates lordosis is by remodeling synaptic connectivity within the VMH. For instance, estrogen alters VMH dendritic spine density. Little is known, however, about the local VMH microcircuitry governing lordosis nor how estrogen alters synaptic connectivity within this local circuit to facilitate sexual behavior. The goal of this study was to define better the neuron types within the VMH microcircuitry and to examine whether estrogen alters synaptic connectivity, as measured by dendritic spine density, on VMH projection neurons. A retrograde tracer was injected into the PAG of ovariectomized rats treated with vehicle or estradiol. Retrogradely labeled VMH neurons were filled with Lucifer yellow, then immunostained for estrogen receptor-alpha (ER alpha). VMH neurons that project to the PAG had more dendrites than functionally unidentified neurons. Additionally, VMH projection neurons could be subdivided into those located within the cluster of ER alpha-containing neurons and those medial to the cluster. Estrogen decreased spine density by 57% on the long primary dendrites of VMH projection neurons located within the ER alpha cluster but not on projection neurons medial to the cluster. Only 4% of the VMH projection neurons expressed ER alpha. These results suggest that estrogen may facilitate sexual behavior by decreasing spines selectively, via an indirect mechanism, on a subset of VMH neurons that project to the PAG.

The organizational and activational effects of sex hormones on tactile and thermal hypersensitivity following lumbar nerve root injury in male and female rats

“…There is evidence for gonadal hormone stimulation of neurogenesis (Breedlove et al, 1983;Nordeen et al, 1985) and apoptosis (Nilsen et al, 2000), synapse formation (McEwen et al, 2001) and synapse elimination (Calizo and Flanagan-Cato, 2002), neuropeptide expression (De Vries, 1990), and glial modulation (Drew and Chavis, 2000;McCarthy et al,2002). The seemingly ubiquitous and contradictory nature of all of these actions has confounded the development of a singular mechanistic hypothesis that accounts for the effects of gonadal hormones in the modulation of nociceptive sensitivity.…”

Gonadal hormone modulation of dendrites in the mammalian CNS

“…As such, it is possible that by differentially increasing or decreasing spine density on different portions of the dendritic tree, estrogen may finetune synaptic inputs to VNMvl neurons in a way that facilitates lordosis or other female sexual behaviors. In support of this suggestion, subsequent research has shown that the estrogen-responsive VMNvl neurons with long ventrolateral dendrites are projection neurons that send axons to the midbrain periaquaductal gray (PAG; Calizo and Flanagan-Cato, 2002), a connection essential in mediating the lordosis posture (Sakuma and Pfaff, 1979;Hennessey et al, 1990).…”

Sex differences in projections from preoptic area aromatase cells to the periaqueductal gray in Japanese quail

“…The two studies are even more consistent if you consider the possibility that the cells accumulating [ 3 H] testosterone may be labeling cells expressing estrogen receptors as well as androgen receptors, since testosterone could have easily been aromatized into 17 beta-estradiol before binding to the preoptic cells. Interestingly, in the ventromedial nucleus of female rats, cell types defined based on the expression of estrogen receptor-alpha and a high density of spines have also been found to preferentially project to the PAG and these specific defined projections have been related to the hormonal activation of female-typical sexual behaviors (Calizo and Flanagan-Cato, 2002). However, comparable studies in males were not conducted in this case.…”