Seasonal Plasticity within the Gonadotropin-Releasing Hormone (GnRH) System of the Ewe: Changes in Identified GnRH Inputs and Glial Association

Abstract

The annual reproductive cycle in sheep may reflect a functional remodeling within the GnRH system. Specifically, changes in total synaptic input and association with the polysialylated form of neural cell adhesion molecule have been observed. Whether seasonal changes in a specific subset(s) of GnRH inputs occur or whether glial cells specifically play a role in this remodeling is not clear. We therefore examined GnRH neurons of breeding season (BS) and nonbreeding season (anestrus) ewes and tested the hypotheses that specific (i.e. gamma-aminobutyric acid, catecholamine, neuropeptide Y, or beta-endorphin) inputs to GnRH neurons change seasonally, and concomitant with any changes in neural inputs is a change in glial apposition. Using triple-label immunofluorescent visualization of GnRH, glial acidic fibrillary protein and neuromodulator/neural terminal markers combined with confocal microscopy and optical sectioning techniques, we confirmed that total numbers of neural inputs to GnRH neurons vary with season and demonstrated that specific inputs contribute to these overall changes. Specifically, neuropeptide Y and gamma-aminobutyric acid inputs to GnRH neurons increased during BS and beta-endorphin inputs were greater during either anestrus (GnRH somas) or BS (GnRH dendrites). Associated with the changes in GnRH inputs were seasonal changes in glial apposition, glial acidic fibrillary protein density, and the thickness of glial fibrils. These findings are interpreted to suggest an increase in net stimulatory inputs to GnRH neurons during the BS contributes to the seasonal changes in GnRH neurosecretion and that this increased innervation is perhaps stabilized by glial processes.

Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: Implications for a common fertility disorder

“…Possible alterations in GABAergic drive were investigated because anatomical (23,24) and functional (25-28) evidence indicates GABAergic neurons play a role in the synaptic regulation of GnRH neurons. Both frequency and size of GABAergic PSCs were increased in PNA females, suggesting that one mechanism for reproductive dysfunction in these animals may be altered GABAergic drive to GnRH neurons.…”

“…A large body of work suggests that ␥-aminobutyric acid (GABA)ergic afferents play a role in mediating steroid feedback (18)(19)(20)(21)(22). Although those studies could not examine the role of GABA directly on GnRH neurons, anatomical (23,24) and functional (25)(26)(27)(28) work indicates that direct regulation of GnRH neurons by means of the GABA A receptor (GABA A R) occurs. GABA inhibits most mature neurons, but this is controversial for GnRH neurons.…”

Endogenous Activation of Metabotropic Glutamate Receptors Modulates GABAergic Transmission to Gonadotropin-Releasing Hormone Neurons and Alters Their Firing Rate: A Possible Local Feedback Circuit

“…The present results suggest a novel role for mGluRs: to inhibit GABAergic transmission directly to GnRH neurons. Because of the dominance of GABAergic contacts and synaptic transmission to these neurons (Sim et al, 2000;Jansen et al, 2003;, mGluRs may substantially impact GnRH neuron activity.…”

“…GnRH neurons receive a substantial portion of their synaptic input from GABA afferents (Leranth et al, 1985;Jansen et al, 2003;Pompolo et al, 2003). Functional GABAergic synaptic transmission to GnRH neurons via ionotropic GABA A receptors varies as a function of reproductive state, and these changes may help drive reproductive cycles and transitions between fertile and infertile conditions (Sim et al, 2000;Moenter, 2004a,b, 2005).…”

Neuronal-glial plasticity in gonadotropin-releasing hormone release in adult female rats: role of the polysialylated form of the neural cell adhesion molecule

“…The present results suggested a mechanism whereby large quantities of PSA on extracellular surfaces would attenuate adhesion via physical impedance or charge repulsion, thus allowing dynamic structural modifications in GnRH neurons. In several recent reports, PSA-NCAM has been considered a necessary permissive substrate which facilitates morphological neuronal and glial plasticity (Viguie et al 2001, Jansen et al 2003, Theodosis et al 2004, allowing hypothalamic neurons and their synapses to undergo structural changes whenever the proper stimulus intervenes. Besides acting as a permissive molecular factor, PSA-NCAM, by permitting or inhibiting neuronal glial remodeling, may also be affecting the presence of astrocytic processes in the external zone of the ME.…”