title: Depolarising and hyperpolarising actions of GABA(A) receptor activation on gonadotrophin-releasing hormone neurones: towards an emerging consensus.
abstract: The gonadotrophin-releasing hormone (GnRH) neurones represent the final output neurones of a complex neuronal network that controls fertility. It is now appreciated that GABAergic neurones within this network provide an important regulatory influence on GnRH neurones. However, the consequences of direct GABA(A) receptor activation on adult GnRH neurones have been controversial for nearly a decade now, with both hyperpolarising and depolarising effects being reported. This review provides: (i) an overview of GABA(A) receptor function and its investigation using electrophysiological approaches and (ii) re-examines the past and present results relating to GABAergic regulation of the GnRH neurone, with a focus on mouse brain slice data. Although it remains difficult to reconcile the results of the early studies, there is a growing consensus that GABA can act through the GABA(A) receptor to exert both depolarising and hyperpolarising effects on GnRH neurones. The most recent studies examining the effects of endogenous GABA release on GnRH neurones indicate that the predominant action is that of excitation. However, we are still far from a complete understanding of the effects of GABA(A) receptor activation upon GnRH neurones. We argue that this will require not only a better understanding of chloride ion homeostasis in individual GnRH neurones, and within subcellular compartments of the GnRH neurone, but also a more integrative view of how multiple neurotransmitters, neuromodulators and intrinsic conductances act together to regulate the activity of these important cells.
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin, New Zealand. allan.herbison@otago.ac.nz
authors.forename: A E
authors.initials: AE
authors.lastname: Herbison
authors.forename: S M
authors.initials: SM
authors.lastname: Moenter
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000328:Adult; D000818:Animals; D032921:Consensus; D058785:GABA-A Receptor Agonists / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D007987:Gonadotropin-Releasing Hormone