Poster Presentation The International Congress of Neuroendocrinology 2014

Modification of a robust neuronal circuit between arcuate GABA neurons and GnRH neurons in a mouse model of polycystic ovarian syndrome (#355)

Aleisha M Moore 1 , Mel Prescott 1 , Rebecca E Campbell 1
  1. University of Otago, Dunedin, New Zealand

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women of reproductive age worldwide. An increase in luteinising hormone (LH) pulse frequency associated with PCOS is suggestive of changes in gonadotropin-releasing hormone (GnRH) neuron regulation. Previously, we have shown in a mouse model of PCOS generated by prenatal androgen (PNA) exposure that GnRH neurons receive a greater number of GABAergic inputs. As GABAergic input to GnRH neurons is postulated to be excitatory, this may contribute to the suggested increase in GnRH neuron activity. However, the identity of the specific GABAergic neuronal populations regulating GnRH neuron activity remains largely unknown. In this study, we targeted GABAergic neurons within the arcuate nucleus (ARC) by injecting an adenoviral vector expressing farnesylated enhanced green fluorescent protein (EGFPf) into the ARC of vesicular GABA transporter (VGaT)-Cre mice. Immunofluorescent labelling of EGFPf and GnRH neurons was performed, and 20 GnRH neurons per animal were analysed for close appositions using confocal microscopy. Remarkably, ARC GABAergic projections were found to robustly contact GnRH neurons. In vehicle-treated control (n=6) and PNA-treated (n=5) mice, 61.6±8.1% and 60.8±10.5% of GnRH neurons closely apposed long-range projections from ARC GABAergic neurons, respectively. ARC GABAergic fibers were found to either contact GnRH neurons at single points, form multiple contacts along the soma and dendrites, or unexpectedly, bundle with GnRH neuron dendrites. Interestingly, we also discovered that the density of ARC GABAergic fibers apposing the primary dendrite of GnRH neurons within the rostral preoptic area was significantly increased in PNA-treated mice compared to controls (p<0.05). These anatomical findings suggest a key functional role for ARC GABAergic neurons in the regulation of fertility and suggest that an increase in this circuit may be responsible for the elevated LH pulse frequency characteristic of PCOS.