title: Gap junctions between neuronal inputs but not gonadotropin-releasing hormone neurons control estrous cycles in the mouse.
abstract: The role of gap junctions in the neural control of fertility remains poorly understood. Using acute brain slices from adult GnRH-green fluorescent protein transgenic mice, individual GnRH neurons were filled with a mixture of fluorescent dextran and neurobiotin. No dye transfer was found between any GnRH neurons, although approximately 30% of GnRH neurons exchanged neurobiotin with closely apposed cells. Dual electrophysiological recordings from pairs of GnRH neurons revealed an absence of electrical coupling. Using adult connexin 36 (Cx36)-cyan fluorescent protein transgenic mice, Cx36 was identified in cells within several hypothalamic brain regions, including 64% of preoptic area kisspeptin neurons but not in GnRH neurons. To assess the potential role of Cx36 in non-GnRH neurons within the GnRH neuronal network (i.e. neurons providing afferent inputs to GnRH neurons), a calmodulin kinase IIα-Cre (CKC)-LoxP strategy was used to generate mice with a neuron-specific deletion of Cx36 beginning in the first postnatal week. Mutant female mice exhibited normal puberty onset but disordered estrous cyclicity, although their fecundity was normal as was their estrogen-negative and -positive feedback mechanisms. The effects of adult deletion of Cx36 from neurons were assessed using a tamoxifen-dependent inducible CKC-Cx36 transgenic strategy. Mutant mice exhibited the same reproductive phenotype as the CKC-Cx36 animals. Together these observations demonstrate that there is no gap junctional coupling between GnRH neurons. However, it is apparent that other neurons within the GnRH neuronal network, potentially the preoptic kisspeptin neurons, are dependent on Cx36 gap junctions and that this is critical for normal estrous cyclicity.
authors: Centre for Neuroendocrinology, Department of Physiology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
authors: Rebecca E
authors: RE
authors: Campbell
authors: Eric
authors: E
authors: Ducret
authors: Robert
authors: R
authors: Porteous
authors: Xinhuai
authors: X
authors: Liu
authors: Michel K
authors: MK
authors: Herde
authors: Kerstin
authors: K
authors: Wellerhaus
authors: Stephan
authors: S
authors: Sonntag
authors: Klaus
authors: K
authors: Willecke
authors: Allan E
authors: AE
authors: Herbison
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D030762:Estrous Cycle; D005260:Female; D017629:Gap Junctions / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D051379:Mice / Q000235:genetics / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D000097004:Gap Junction delta-2 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D007987:Gonadotropin-Releasing Hormone; D000097004:Gap Junction delta-2 Protein