Whole-cell recordings from preoptic/hypothalamic slices reveal burst firing in gonadotropin-releasing hormone neurons identified with green fluorescent protein in transgenic mice

Central control of reproduction is governed by a neuronal pulse generator t hat underlies the activity of hypothalamic neuroendocrine cells that secret e GnRH. Bursts and prolonged episodes of repetitive action potentials have been associated with hormone secretion in this and other neuroendocrine sys tems. To begin to investigate the cellular mechanisms responsible for the G nRH pulse generator, we used transgenic mice in which green fluorescent pro tein was genetically targeted to GnRH neurons. Whole-cell recordings were o btained from 21 GnRH neurons, visually identified in 200-mu m preoptic/hypo thalamic slices, to determine whether they exhibit high frequency bursts of action potentials and are electrically coupled at or near the somata. All GnRH neurons fired spontaneous action potentials, and in 15 of 21 GnRH neur ons, the action potentials occurred in single bursts or episodes of repetit ive bursts of high frequency spikes (9.77 +/- 0.87 Hz) lasting 3-120 sec. E xtended periods of quiescence of up to 30 min preceded and followed these p eriods of repetitive firing. Examination of 92 GnRH neurons (including 32 n eurons that were located near another green fluorescent protein-positive ne uron) revealed evidence for coupling in only 1 pair of GnRH neurons. The ev idence for minimal coupling between these neuroendocrine cells suggests tha t direct soma to soma transfer of information, through either cytoplasmic b ridges or gap junctions, has a minor role in synchronization of GnRH neuron s. The pattern of electrical activity observed in single GnRH neurons withi n slices is temporally consistent with observations of GnRH release and mul tiple unit electrophysiological correlates of LH release. Episodes of burst firing of individual GnRH neurons may represent a component of the GnRH pu lse generator.