Neuroanatomical plasticity in the gonadotropin‐releasing hormone system of the ewe: Seasonal variation in glutamatergic and γ‐aminobutyric acidergic afferents

Abstract

Temperate zone animals time the onset of reproductive events to coincide with specific portions of the sidereal year. Although the neural mechanisms involved remain poorly understood, a marked annual variation in the brain's sensitivity to estradiol negative feedback is thought to mediate many of the changes in neuroendocrine hormone secretion, especially that of the gonadotropin-releasing hormone (GnRH) neurons, via neural afferents. The aim of the present study was to determine whether glutamatergic inputs to GnRH neurons in sheep vary seasonally and to expand our previous observations of seasonal changes in gamma-aminobutyric acid (GABA)-ergic inputs. Brains from adult sheep were collected during the breeding season (N = 8) or the nonbreeding season (anestrus; N = 7). Confocal microscopy and optical sectioning were used to quantify the density of labeled VGLUT2 and VGAT immunoreactivity onto GnRH neurons. The results reveal a significantly greater number of VGLUT2-ir inputs to GnRH dendrites during the breeding season vs. the nonbreeding season but no seasonal changes on GnRH cell somas. The number of VGAT-ir terminals onto GnRH dendrites was reduced in the breeding season compared with the nonbreeding season. GnRH neurons were also found to receive dual-phenotype (VGLUT + VGAT) inputs; these varied with season in a manner similar to VGAT inputs. Morphologically, the numbers of branches of proximal dendrites increased significantly in a subset of GnRH neurons located near the midline. Together these results reveal a dynamic seasonal reorganization of identified inputs onto GnRH neurons and lend additional support to the overall hypothesis that seasonal modulation of GnRH neurons involves glutamatergic and GABAergic neural plasticity.

Physiology of the Adult Gonadotropin-Releasing Hormone Neuronal Network

“…220 Although not in agreement with previous and subsequent studies that found no evidence for vGlut2 protein in GnRH neurons, 35,221 another investigation found that a vGlut2 promoter construct directed expression to a subpopulation of GnRH neurons located in the medial septum of the mouse. 220 Although not in agreement with previous and subsequent studies that found no evidence for vGlut2 protein in GnRH neurons, 35,221 another investigation found that a vGlut2 promoter construct directed expression to a subpopulation of GnRH neurons located in the medial septum of the mouse.…”

“…However, it should be noted that not all GnRH neurons exhibit this simple bipolar morphology. 35 Cell filling experiments in transgenic GnRH-green fluorescent protein (GFP) mice have revealed that GnRH neurons exhibit remarkably long dendrites that can extend for over 2000 μm 36 (Figure 11.2(D)). 32 There is also growing appreciation that the dendritic morphology of a GnRH neuron is modifiable; a notable rearrangement of dendritic structure occurs in the mouse around the time of puberty, 33,34 and seasonal differences have also been observed in the sheep.…”

“…91,[369][370][371][372] The sources of GABA inputs to GnRH neurons remain poorly defined. 35 More recent electrophysiological studies have shown that functional GABA A receptors exist at least up to 200 μm along the proximal dendrite 118 as well as on the dendron as it enters the ME. These inputs are likely to co-express a variety of other neuropeptides, and a recent investigation has demonstrated the frequency-dependent coding of GABA versus neuropeptide release from such afferents to GnRH neurons.…”

Perineuronal nets and GABAergic cells in the inferior colliculus of guinea pigs

“…Moreover, it was present in primary omission controls, indicating binding of the secondary antibody to these cells. Since we used the VGLUT2 antibody to stain terminals, but not somata, we disregarded this cellular staining (Sergeeva and Jansen, 2009). An antibody to neuronal nucleus specific antigen (NeuN) was used as a neuron specific counterstain (diluted 1:500, Millipore, ABN78).…”

Opposite-sex housing reactivates the declining GnRH system in aged transgenic male mice with FGF signaling deficiency

“…LR-5 was previously validated for specificity to GnRH1 (48). For the adult mice, GnRH neuronal counts and morphological assessments were performed on all 20 sections rostral (1.2 mm) and all 40 sections caudal (2.4 mm) to the organum vasculosum of the lamina terminalis (OVLT).…”