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      Estradiol Induces Diurnal Shifts in GABA Transmission to Gonadotropin-Releasing Hormone Neurons to Provide a Neural Signal for Ovulation

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          Abstract

          Ovulation is initiated by a surge of gonadotropin-releasing hormone (GnRH) secretion by the brain. GnRH is normally under negative feedback control by ovarian steroids. During sustained exposure to estradiol in the late follicular phase of the reproductive cycle, however, the feedback action of this steroid switches to positive, inducing the surge. Here, we used an established ovariectomized, estradiol-treated (OVX+E) mouse model exhibiting daily surges to investigate the neurobiological mechanisms underlying this switch. Specifically, we examined changes in GABA transmission to GnRH neurons, which can be excited by GABA A receptor activation. Spontaneous GABAergic postsynaptic currents (PSCs) were recorded in GnRH neurons from OVX+E and OVX mice in coronal and sagittal slices. There were no diurnal changes in PSC frequency in cells from OVX mice in either slice orientation. In OVX+E cells in both orientations, PSC frequency was low during negative feedback but increased at surge onset. During the surge peak, this increase subsided in coronal slices but persisted in sagittal slices. Comparison of PSCs before and during tetrodotoxin (TTX) treatment showed TTX decreased PSC frequency in OVX+E cells in sagittal slices, but not coronal slices. This indicates estradiol acts on multiple GABAergic afferent populations to increase transmission through both activity-dependent and -independent mechanisms. Estradiol also increased PSC amplitude during the surge. Estradiol and the diurnal cycle thus interact to induce shifts in both GABA transmission and postsynaptic response that would produce appropriate changes in GnRH neuron firing activity and hormone release.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          21 February 2007
          : 27
          : 8
          : 1913-1921
          Affiliations
          [1]Neuroscience Graduate Program, Departments of Medicine and Cell Biology, University of Virginia, Charlottesville, Virginia 22908
          Author notes
          Correspondence should be addressed to Suzanne M. Moenter, P.O. Box 800578, University of Virginia, Charlottesville, VA 22908. moenter@ 123456virginia.edu
          Article
          PMC6673555 PMC6673555 6673555 3193692
          10.1523/JNEUROSCI.4738-06.2007
          6673555
          17314287
          393a6c05-2dc9-4892-82a7-7512920fe9fe
          Copyright © 2007 Society for Neuroscience 0270-6474/07/271913-09$15.00/0
          History
          : 31 October 2006
          : 21 December 2006
          : 18 January 2007
          Categories
          Articles
          Behavioral/Systems/Cognitive
          Custom metadata

          ovulation,GABA,LH,estradiol,postsynaptic current,GnRH
          ovulation, GABA, LH, estradiol, postsynaptic current, GnRH

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