Evidence for Changes in Numbers of Synaptic Inputs onto KNDy and GnRH Neurones during the Preovulatory LH Surge in the Ewe

Abstract

Kisspeptin neurones located in the arcuate nucleus (ARC) and preoptic area (POA) are critical mediators of gonadal steroid feedback onto GnRH neurones. ARC kisspeptin cells that co-localize neurokinin B (NKB) and dynorphin (Dyn), are collectively referred to as KNDy (Kisspeptin/NKB/Dyn) neurones, and have been shown to also co-express the glutamatergic marker, vGlut2, in mice. The ARC in rodents has long been known as a site of hormone-induced neuroplasticity, and changes in synaptic inputs to ARC neurones in rodents occur over the oestrous cycle. Based on this evidence, the goal of this study was to examine possible changes across the ovine oestrous cycle in synaptic inputs onto kisspeptin cells in the ARC (KNDy) and POA, and inputs onto GnRH neurones. Gonadal-intact breeding season ewes were perfused using 4% paraformaldehyde during either the luteal or follicular phase of the oestrous cycle, the latter group sacrificed at the time of the luteinising (LH) surge. Hypothalamic sections were processed for triple-label immunodetection of kisspeptin/vGlut2/synaptophysin or kisspeptin/vGlut2/GnRH. The total numbers of synaptophysin- and vGlut2-positive inputs to ARC KNDy neurones were significantly increased at the time of the LH surge compared to luteal phase; as these did not contain kisspeptin they do not arise from KNDy neurons. In contrast to the ARC, the total number of synaptophysin-positive inputs onto POA kisspeptin neurones did not differ between luteal phase and surge animals. The total number of kisspeptin and vGlut2 inputs onto GnRH neurones in both the POA and mediobasal hypothalamus was also increased during the LH surge. Taken together, these results provide novel evidence of synaptic plasticity at the level of inputs onto KNDy and GnRH neurones during the ovine oestrous cycle, changes which may contribute to the generation of the preovulatory GnRH/LH surge.

Mapping GABA and glutamate inputs to gonadotrophin‐releasing hormone neurones in male and female mice

“…Brain slice recordings support these findings, indicating that GnRH neurones from female mice in negative‐ and positive‐feedback states do not exhibit differences in glutamatergic post‐synaptic currents . However, species differences may exist because VGLUT2 positive inputs to GnRH neurones are reported to increase at the time of the LH surge in the ewe …”

Neuroanatomical Relationship of Neuronal Nitric Oxide Synthase to Gonadotropin-Releasing Hormone and Kisspeptin Neurons in Adult Female Sheep and Primates

“…Kisspeptin is a potent stimulator of GnRH and LH secretion [9][10][11][12], and kisspeptin neurons contain both ERα [13,14] and progesterone receptors [15]. Moreover, GnRH neurons express KISS1R [16,17] and kisspeptincontaining fibers have been observed in direct apposition to GnRH neurons [18][19][20]. Thus, kisspeptin has the ability to directly communicate the actions of ovarian steroids to GnRH neurons and influence GnRH and LH secretion.…”

An integrative view of mammalian seasonal neuroendocrinology

“…In mouse, approximately 90% of neurones expressing Kiss1 in the arcuate nucleus are glutamatergic, even though a substantial fraction may also use GABA . In sheep, Kiss1 ‐expressing neurones are also mostly glutamatergic . In mouse, there is good evidence that Npvf neurones are glutamatergic too, and also that distinct subpopulations of Npvf neurones may exist .…”

“…181 In sheep, Kiss1-expressing neurones are also mostly glutamatergic. 183 In mouse, there is good evidence that Npvf neurones are glutamatergic too, 108 and also that distinct subpopulations of Npvf neurones may exist. 184 No data are available in sheep or hamsters regarding the neurochemical identity of Npvfexpressing neurones or the existence of neuronal subpopulations.…”