The Electrophysiology of the Hypothalamic Gonadotropic Hormone Releasing Hormone (GnRH) Pulse Generator in the Rhesus Monkey

Abstract

The rhythmic pulsatile nature of gonadotropic hormone section first noted in the ovariectomized rhesus monkey (Dierschke et al., 1970) has since been described in every mammal studied in this regard (Pohl and Knobil, 1982). The original supposition that each gonadotropin pulse is the consequence of a pulse of GnRH released by the hypothalamus into the pituitary portal circulation has been amply confirmed (Carmel et al., 1976; Clarke and Cummins, 1982). These findings have given rise to the concept of a neuronal construct in the central nervous system which is responsible for the rhythmic activation of GnRH cells and the release of the neuropeptide from their terminals. While this system has been variously referred to as an oscillator or pulse generator for descriptive convenience, its cellular nature remains unknown. In the rhesus monkey, using conventional neuroendocrinological techniques, the pulse generator has been localized to the mediobasal hypothalamus (MBH) (Krey et al., 1975), and more specifically, to the area of the arcuate nucleus (Plant et al., 1978). An effort to detect the electrophysical basis of pulse generator activity was initiated in the late 1970’s and was based on the supposition that each bolus of GnRH released into the pituitary portal circulation must be the consequence of the synchronous firing of a large number of GnRH cells and that the approach most likely to detect their action potentials was the application of multiunit recording techniques as utilized earlier for the study of the macrocellular system in the rhesus monkey by Hayward and his colleagues (Hayward, 1977). Our initial approach utilizing single tungsten electrodes acutely placed in the region of the arcuate nucleus of anesthetized rhesus monkeys, while largely unsuccessful, occasionally yielded evidence of astonishing increases in multiunit electrical activity (MUA) coupled with pulses of LH as measured in the peripheral circulation (Dufy et al., 1979; Knobil, 1981). We assumed that the rarity of successful electrode placements were attributable to the sparsity of the active units in the hypothalamus and changed our strategy to the stereotaxic bilateral implantation of chronic multiple electrode arrays which blanketed the MBH (Wilson et al., 1984). This new approach yielded predictable results from one or more electrodes in most animals and permitted the systematic study of the pulse generator by direct, electrophysiological observation.