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Endocrinology Vol. 143, No. 6 2284-2292
Copyright © 2002 by The Endocrine Society

NEUROENDOCRINOLOGY

Estradiol-Sensitive Afferents Modulate Long-Term Episodic Firing Patterns of GnRH Neurons

Craig S. Nunemaker, R. Anthony DeFazio and Suzanne M. Moenter

Departments of Internal Medicine and Cell Biology and National Science Foundation Center for Biological Timing, University of Virginia, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Suzanne M. Moenter, Department of Internal Medicine, P.O. Box 800578, Jefferson Park Avenue, University of Virginia, Charlottesville, Virginia 22908. E-mail: . smm4n{at}virginia.edu

GnRH neurons comprise the final common pathway of an estrogen-sensitive pattern generator controlling fertility. To determine estradiol effects on GnRH neuron firing patterns, adult transgenic mice were ovariectomized (OVX), and half were treated with estradiol (OVX+E). One week later targeted single-unit extracellular recordings were made from GnRH neurons identified by green fluorescent protein expression. Estradiol markedly affected GnRH neuron firing patterns, increasing the percentage and duration of time these cells were quiescent (<=1 action current/min). Estradiol increased the interval between episodes of increased firing rate determined by Cluster analysis of recordings more than 45 min (OVX+E 38.8 ± 7.2 min, OVX 16.7 ± 2.1 min, n = 6 each). Possible mechanisms of estradiol modulation were examined by simultaneously blocking ionotropic secretion of {gamma}-aminobutyric acid and glutamatergic receptors. This treatment had no effect on cells from OVX mice (n = 10), indicating episodic firing of GnRH neurons is not driven by activation of these receptors. Receptor blockade eliminated estradiol effects on GnRH neurons in the midventral preoptic area (n = 7) but not elsewhere (n = 7). Individual GnRH neurons thus display episodic firing patterns at intervals previously reported for secretory pulses. Estradiol modulates episode frequency to exert feedback control; in a substantial subset of GnRH neurons, estradiol feedback is enforced via GABAergic and/or glutamatergic afferents.




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