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Gonadotropin-Releasing Hormone Neurons Generate Interacting Rhythms in Multiple Time Domains

Departments of Internal Medicine and Cell Biology, National Science Foundation Center for Biological Timing (C.S.N., M.S., R.A.D.F., S.M.M.), and the Center for Biomathematical Technology (M.S.), 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.

Pulsatile release of GnRH is prerequisite for fertility. The possibility that multiple rhythms interact to generate GnRH pulses was raised by observations of changes in action potential firing and intracellular calcium levels occurring much more frequently than hormone pulses. To examine this further, we analyzed firing patterns from targeted extracellular recordings of green fluorescent protein-expressing GnRH neurons in acute brain slices prepared from adult ovariectomized and ovariectomized +estradiol mice. Fourier spectral analysis identified rhythms in multiple time domains, which we grouped into bursts (a period of <100 sec), clusters (100–1000 sec), or episodes (>1000 sec). Bursts were the fundamental unit of activity and consisted of trains of action currents (the currents during action potentials). Episodes and clusters were lower frequency changes in firing rate resulting from alterations in the time between bursts. Specifically, mean interburst interval during episode peaks was less than during nadirs. In contrast, neither burst duration nor action currents/burst differed between peaks and nadirs. Estradiol increased episode period by changing the patterning of bursts, not burst duration or action currents/burst. We propose a low frequency rhythm that is subject to external influences alters the patterning of a fundamental unit of activity to change ultimately GnRH pulse frequency.

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