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Submitted on June 28, 2005
Accepted on August 17, 2005
Department of Internal Medicine and Cell Biology, University of Virginia, Charlottesville, VA 22908; Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL 33136
* To whom correspondence should be addressed. E-mail: smm4n{at}virginia.edu.
-aminobutyric acid (GABA) provides a major synaptic input to GnRH neurons. GnRH neurons maintain high intracellular chloride levels and respond to exogenous GABA with depolarization and action potential firing. We examined the role of synaptic GABA type-A receptor (GABAAR) activation on the firing activity of GnRH neurons. Targeted extracellular recordings were used to detect firing activity of GnRH neurons in brain slices from adult female mice. Since the brain slice preparation preserves both glutamatergic and GABAergic neuronal networks, effects of GABAARs on GnRH neurons were isolated by blocking ionotropic glutamatergic receptors (iGluR). With iGluR blocked, many GnRH neurons remained spontaneously active. Consistent with an excitatory role for GABA, subsequent blockade of GABAARs suppressed firing rate in active cells from diestrous females by 
40% (P < 0.05, n = 10). GABAAR block did not affect inactive cells (n = 7), indicating GABAAR-mediated inhibition was not responsible for the lack of firing. In prenatally androgenized (PNA) females, GnRH neurons exhibit larger, more frequent GABAergic postsynaptic currents than control females. Most cells from PNA animals fired spontaneously and firing rate was suppressed 80% following GABAAR blockade (P < 0.01, n = 8). Blocking GABAAR without blocking iGluRs increased firing rate in GnRH neurons from diestrous females (P < 0.05, n = 6), perhaps attributable to hyperexcitability within the slice network. Our results indicate GABAergic inputs help generate a portion of action potentials in GnRH neurons; this fraction depends on the level of GABA transmission and postsynaptic responsiveness. The complexities of GnRH neuron response to GABA make this a potentially critical integration point for central regulation of fertility.
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