Effects of estrogen on neuronal excitability in the hippocampal-septal-hypothalamic system

The effects of electrical stimulation of the medial preoptic area (MPO) upon unit firing in the periventricular arcuate nucleus, and that of the dorsal hippocampus (DHPC) on medial septo-preoptic and arcuate (ARC) neurons, were investigated in Wistar and Sprague-Dawley female rats throughout the 4-day estrous cycle. Unit activity was recorded using stereotaxically-oriented tungsten microelectrodes under light urethane anesthesia. Repetitive stimulation of monophasic square waves varying only in current intensity was used. The following results were obtained: (a) An increase in activity of all ARC neurons recorded was induced by MPO stimulation on each day of the estrous cycle. (b) The minimum current (threshold) effective in increasing activity in the ARC neurons varied throughout the estrous cycle; the lowest threshold was observed in proestrus and the highest on the first day of diestrus. Also, the threshold current of MPO stimulation required in increase ARC activity was found to be elevated after ovariectomy and markedly reduced to the levels of the proestrous animal by estrogen treatment. (c) Stimulation of the DHPC (field CA3) increased activity in the medial septum but decreased activity in the MPO. Two pools of neurons, one increased and one decreased by DHPC stimulation, were observed in the ARC. (d) Variation in the threshold hippocampal stimulation during the estrous cycle was observed in the response of MPO and ARC neurons (the stimulation was effective only in proestrus and estrus); but not in that of medial septal neurons. (e) In addition, the spontaneous activity of septal; MPO; and ARC neurons was increased at proestrus or after estrogen injection. The present results suggest that plasma levels of estrogen play an essential role in the cyclic process of the regulation of ovulation by way of the selective facilitation of neuronal excitability in specific functional neural pathways. Furthermore, the results support the existence of a hippocampal inhibitory projection originating in field CA3 and terminating in the final common pathway, MPO to ARC.