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The Journal of Neurophysiology Vol. 86 No. 1 July 2001, pp. 86-93
Copyright ©2001 by the American Physiological Society
Departments of Internal Medicine, Cell Biology, and Biology and National Science Foundation Center for Biological Timing, University of Virginia, Charlottesville, Virginia 22908
Nunemaker, Craig S.,
R. Anthony DeFazio,
Michael E. Geusz,
Erik D. Herzog,
Gilbert R. Pitts, and
Suzanne M. Moenter.
Long-Term Recordings of Networks of Immortalized GnRH Neurons
Reveal Episodic Patterns of Electrical Activity. J. Neurophysiol. 86: 86-93, 2001. The CNS controls
reproduction through pulsatile secretion of gonadotropin-releasing
hormone (GnRH). Episodic increases in the firing rate of unidentified
hypothalamic neurons have been associated with downstream markers of
GnRH secretion. Whether this episodic electrical activity is intrinsic
to GnRH neurons, intrinsic to other "pulse generator" neurons that
drive GnRH neurons, or a combination of these is unknown. To determine
if GnRH neurons display episodic firing patterns in isolation from
other cell types, immortalized GnRH neurons (GT1-7 cells) were cultured
on multiple microelectrode arrays. Long-term, multi-site recordings of
GT1-7 cells revealed repeated episodes of increased firing rate with an
interval of 24.8 ± 1.3 (SE) min that were completely eliminated
by tetrodotoxin, a sodium channel blocker. This pattern was comprised
of active units that fired independently as well as coincidentally,
suggesting the overall pattern of electrical activity in GT1-7 cells
emerges as a network property. The A-type potassium-channel antagonist
4-aminopyridine (1 mM) increased both firing rate and GnRH secretion,
demonstrating the presence of A-type currents in these cells and
supporting the hypothesis that electrical activity is associated with
GnRH release. Physiologically relevant episodic firing patterns are
thus an intrinsic property of immortalized GnRH neurons and appear to
be associated with secretion. The finding that overall activity is
derived from the sum of multiple independent active units within a
network may have important implications for the genesis of the GnRH
secretory pattern that is delivered to the target organ. Specifically,
these data suggest not every GnRH neuron participates in each secretory pulse and provide a possible mechanism for the variations in GnRH-pulse amplitude observed in vivo.
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