Masazumi Kawakami

Electrophysiological correlates of pulsatile gonadotropin release in rats.

In order to reveal the electrophysiological correlates of pulsatile LH release in ovariectomized rats, changes in multiple unit activity (MUA) in the arcuate nucleus (ARC), the medial preoptic area, the ventromedial nucleus, the anterior hypothalamic area and other areas of the brain were recorded in lightly anesthetized female rats. Rats were ovariectomized at least 7 weeks prior to the experiment. 0.1 -ml blood samples were withdrawn from a cardiac catheter at 10-min intervals during the recording in order to measure the changes in the plasma LH concentration by radioimmunoassay. The LH concentration showed pulsatile changes under continuous intravenous infusion of thiopental sodium while cortical EEG was stable throughout the experiment. The firing rate in the middle part of the ARC (8 recordings) changed in parallel with the increase in the plasma LH concentration and was abruptly raised just prior to an increase in LH secretion. The number of MUA spike discharges per minute increased to 1.5-5 times that of the basal level. MUA started to increase 2-9 min prior to the LH rise and the high level of MUA lasted for 1-5 min. The firing rate in the ARC (14 recordings) and in other areas (54 recordings) recorded did not change periodically in parallel with the increase in LH. As these changes in MUA were localized in the ARC and were not reflected in cortical EEG, they might be specific local changes distinguished from generalized systemic effects involving the whole brain. These extreme increases in MUA seem to be due to the high activity either of neurons that secrete LH-RH or those that control the secretion of LH-RH.

Changes in Multiple Unit Activity of the Brain During the Estrous Cycle

Electrical activity of the brain during the critical period in the rat was examined throughout the estrous cycle, using chronically implanted macro-micro electrodes. Slight circadian rhythms were observed in the basal level of the integrated multiple unit activity (MUA) in the basal hypothalamus and forebrain limbic area. In addition to these changes, a gradual increase of MUA in the basal hypothalamus was observed during the evening of diestrus day 2, while there was no change in the forebrain limbic preoptic area. However, a characteristic elevated pattern of MUA appeared for 12 to 25 min during the critical period (2 p.m. to 4 p.m.), both in the basal hypothalamus and forebrain limbic preoptic area, i.e., in the arcuate nucleus (ARC), ventromedial hypothalamic nucleus (VMH), medial preoptic area (MPO), septum (SEPT), amygdala (AMYG) and bed nucleus of stria terminalis (BST). The episodes of the characteristic pattern were also observed in the basal hypothalamus on the afternoons of diestrus day 2 and estrus, as well as in the forebrain limbic preoptic area on the day of estrus. To determine the possible relationship between the characteristic pattern and gonadotrophin release, electrochemical stimulation was applied to the areas of the brain where the characteristic pattern was observed during the critical period. Ovulation could be induced by stimulation of the ARC, MPO, SEPT, AMYG, and BST, but not by stimulation of the reticular formation (RF) and hippocampus (HPC). Furthermore, the results shed light on the facilitatory and inhibitory effects of progesterone on ovulation and the onset of the critical period.

Neuro-Correlate of Limbic-Hypothalamo-Pituitary-Gonadal Axis in the Rat: Change in Limbic-Hypothalamic Unit Activity Induced by Vaginal and Electrical Stimulation

The present study deals with the effect of vaginal stimulation (VS) with a glass rod on unit activity in the brain and the correlation of the activity of each area under certain hormonal conditions. T

Responses of Hypothalamic Neurons to the Microiontophoresis of LH-RH, LH and FSH under Various Levels of Circulating Ovarian Hormones

Iontophoretic application of LH-releasing hormone (LH-RH) elicited changes in the activity of 44 out of 74 MBH units. Each unit was recorded from the neurons which were confirmed to send their axons d

Modulating Effect of Limbic Structures on Gonadotropin Release

Serum and pituitary LH and FSH were measured during the estrous cycle, following electrical stimulation of the medial preoptic area (MPO), medial part of the amygdala (AMYG), and dorsal hippocampus (H

Effect of acupuncture on adrenocortical hormone production: I. Variation in the ability for adrenocortical hormone production in relation to the duration of acupuncture stimulation.

The effect of acupuncture on adrenocortical hormone production in adult female albino rabbits of New Zealand strain was investigated. There was significant increase compared to the control cortisol and corticosterone following application of acupuncture at the locus Tsu-San-Li. In the non-locus group, such treatment resulted in only a transient raise followed by a significant fall in cortisol and corticosterone. Acupuncture treatment with electric current for 1 hour proved to be unique in that it gave rise to no biphasic change in the 14C uptake of the steroids. These results indicate that adrenal production of corticosterone and cortisol was enhanced by acupuncture and electroacupuncture at the Tsu-San-Li locus.

Effects of estrogen on the excitability of neurons projecting from the noradrenergic A1 region to the preoptic and anterior hypothalamic area

Estradiol benzoate administered to ovariectomized female rats significantly elevated the mean spontaneous firing rate and frequency of successful antidromic propagation into the somatodendritic spike and significantly reduced the strength of post-stimulus inhibition in presumed A1 noradrenergic neurons projecting directly to the preoptic and anterior hypothalamic area. The occurrence of both antidromic spikes and post-stimulus inhibition of the majority of these neurons was completely abolished by the injection of 6-hydroxydopamine but not by 5, 7-dihydroxytryptamine directly into the medial forebrain bundle.

Reanalysis of the Preoptic Afferents and Efferents Involved in the Surge of LH, FSH and Prolactin Release in the Proestrous Rat

In order to elucidate neural pathways concerned with the proestrous surge of LH, FSH and prolactin (Prl) release, brain transection or lesion was made acutely under ether anesthesia between 12.00 and 14.00 h of proestrus, and electrochemical stimulation was done under anesthesia with pentobarbital sodium (31.5 mg/kg b.w.) injected at 13.45 h. Transection which interrupted the connection of septum (SEPT), diagonal band of Broca (DBB) and bed nucleus of stria terminalis (BST) with the preoptic-suprachiasmatic area interfered with ovulation and surge of release of all 3 hormones. Isolation of the basal part of the suprachiasmatic area, including the suprachiasmatic nucleus (SCH), blocked ovulation also. Bilateral lesions in the medial preoptic area (MPO) with platinium-iridium electrode blocked ovulation and the surge of LH and Prl release, but not of FSH. Lesions in the SCH blocked ovulation and the surge of LH, but not of FSH and Prl. In the rat with acute isolation of the basal part of the suprachiasmatic area and SCH, stimulation of the MPO failed to induce ovulation and LH release, but was followed by FSH release. Prl release was not inhibited as in the intact rat. When the rat had the antero-SCH cut, stimulation of the SCH induced LH release but not FSH, and the inhibition on Prl release was pronounced. These findings offer evidence that the limbic-forebrain inputs are necessary for the preoptic integration in order to stimulate the proestrous surge of LH, FSH and Prl release. Furthermore, it is possible that separate pathways from the preoptic area to the medial basal hypothalamus are concerned in the stimulation of individual hormones--a restricted route for LH which may pass through the SCH, a diffuse one for FSH which may pass through either the SCH or anterior hypothalamic area, and a relatively diffuse one for Prl which may pass outside the SCH.

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.

Electrophysiological evidences for possible participation of periventricular neurons in anterior pituitary regulation.

Unit activity of neurons in the periventricular area of the third ventricle (PVA), in which the organum vasculosum laminae terminalis is included, was recorded in female rats in proestrus. The units were antidromically driven by electrical stimulation of the arcuate-median eminence region (ARC-ME). In the antidromic responses, a notch was generally observed in the rising phase of the driven wave, and fractionation of A- and B-components at the notch was readily elicited by applying repetitive stimulatory pulses at frequencies higher than 10 Hz, or successive double pulses with intervals less than 3.5 msec. At the same time, ARC-ME efferents to the PVA were suggested by orthodromic responses in the PVA to ARC-ME stimulation. Occasionally, anti- and orthodromic responses appeared in one electrode, indicating a proximate distribution of these two types of neurons in the PVA. Repetitive stimulation of the ARC-ME at 50 Hz facilitated the orthodromically driven units, whereas antidromically driven units were inhibited. This seems to imply that the orthodromic responses might be recorded from an inhibitory interneuron in the ARC-ME efferent pathway to the PVA, judging from the identical time course of the responses of the two types of the units. Both the anti- and orthodromically driven units were tested with microiontophoresis of LH-RH, TRH, LH, FSH and prolactin. Orthodromically driven units showed no response to microiontophoresis of any hormone. In the antidromically driven units, microiontophoresis of LH-RH and FSH elicited inhibition in 15 and 18% of the tests, and facilitation was seen in 15-25% of the tests in response to LH, TRH and prolactin. The demonstration that local application of hypothalamic and pituitary hormones exerts direct effects on the activity of the PVA neurons which send their axons directly to the ARC-ME, provides additional evidence that the PVA may participate in anterior pituitary regulation.