Electrophysiological and pharmacological profile of Gonadotropin Inhibitory Hormone-expressing neurons in the rat. — ASN Events
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  3. Electrophysiological and pharmacological profile of Gonadotropin Inhibitory Hormone-expressing neurons in the rat.

Electrophysiological and pharmacological profile of Gonadotropin Inhibitory Hormone-expressing neurons in the rat. (#115)

Jack T Pryor 1 , Ishwar S Parhar 2 , David C Spanswick 1 3 , Iain J Clarke 3
  1. Warwick Medical School, University of Warwick, Coventry, UK
  2. Brain Research Institute, School of Medicine and Health Sciences, Monash University Sunway Campus, Selangor, Malaysia
  3. Department of Physiology, Monash Obesity and Diabetes Institute, Monash University, Melbourne, Australia

Gonadotropin Inhibitory Hormone (GnIH) expressing neurons, through projections and interactions with gonadotropin releasing hormone (GnRH)-expressing and POMC-expressing neurons in the arcuate nucleus of the hypothalamus are suggested to serve as a fulcrum for neuroendocrine regulation of reproduction and appetite.  Relatively little is known of the intrinsic membrane and extrinsic synaptic mechanisms regulating activity of GnIH neurons. Here, using the whole-cell patch clamp technique, the electrophysiological and pharmacological profile of GFP-labelled GnIH neurons has been investigated in rats in vitro.

Whole-cell recordings were obtained from 35 GnIH-GFP expressing neurons of the rat dorsomedial hypothalamus (DMH). Passive membrane properties included a mean resting membrane potential, firing rate and input resistance of 39.3 ± 0.7 mV, 0.94 ± 0.18 Hz and 1489 ± 98 mΩ, respectively. DMH GnIH neurons expressed: a 4-AP-sensitive transient outward rectification in 91% neurons; a Cs+-sensitive hyperpolarisation activated conductance in 57% of neurons; a Ni2+ sensitive T-type calcium conductance found in 74% of GnIH neurons. The AMPA receptor antagonist NBQX (10µM; n=5) and the GABA receptor antagonist bicuculine (20µM; n=5) revealed both GABAergic and glutamatergic synaptic connections to GnIH neurons.

Thyrotropin-releasing hormone (TRH; 400nM) induced depolarisation in all neurons tested (n=7) associated with a decrease in input resistance and reversal potential around 0mV, indicating activation of a non-selective cation conductance. Conversely, 5-HT (50µM) induced membrane hyperpolarisation 9 of 14 neurons, associated with a decrease in input resistance and reversal potential around -90mV consistent with activation of one or more K+ conductances. 5-HT-induced depolarisation in 5 neurons was associated with an increase in input resistance and reversal potential around –90 mV, suggesting block of one or more K+ conductances.

These data provide the first description of the intrinsic membrane properties and extrinsic synaptic/neuromodulatory mechanisms regulating excitability of GnIH neurons.