Activity In Paraventricular Nucleus Research Articles

Neuronal expression of Fos protein in the hypothalamus of rats with heart failure

We sought to identify the areas that have altered neuronal activity within the hypothalamus of rats with heart failure (HF) by mapping neuronal staining of c-Fos protein (Fos) 6–8 weeks following coronary artery ligation (HF group; n=17) or sham surgery (sham-operated control group, n=15). Fos-like immunoreactivity was observed in the paraventricular nucleus (PVN), supraoptic nucleus (SON), median preoptic nucleus (MnPO), anterior hypothalamus (AH) and posterior hypothalamus (PH) using a standard ABC immunocytochemical protocol. The rats in the HF group displayed infarcts averaging 34±2% of the outer circumference and 41±1% of the inner circumference of the left ventricular wall. Sham-operated control rats had no observable damage to the myocardium. Rats with chronic heart failure ( n=5) but no manipulation (no surgery) had a similar number of Fos-staining cells in PVN SON, MnPO, AH and PH compared to sham-operated rats. Acute surgery for isolation of vagus nerves and anesthesia for 90 min increased the number of Fos positive cells in PVN, SON and MnPO of both sham-operated rats and rats with HF. Furthermore, rats with heart failure ( n=5) had significantly higher number of Fos-staining cells in PVN (four times), SON (4.5 times) and MnPO (1.5 times) compared to sham-operated rats after acute surgery for isolation of the vagus. The number of Fos-staining cells remained unaltered in AH and PH in both groups of rats. However, in a third series of experiments vagotomy reduced the number of Fos-staining cells in the PVN, SON or MnPO of rats with HF ( n=5) to those observed in sham-operated vagotomized rats. This study shows that: (1) there is augmented neuronal activity as indicated by increased number of Fos staining neurons in the PVN, SON and MnPO due to acute surgical stress in rats with HF, and (2) vagal afferents are responsible for the increased neuronal activity in PVN, SON and MnPO of rats with HF during acute surgical stress. These data support the conclusion that vasopressin producing neurons and autonomic areas within the hypothalamus influenced by vagal afferents are activated during HF and are sensitive to ‘acute surgical stress’ and may contribute to the elevated levels of vasopressin and sympatho-excitation commonly observed in heart failure.

AT(1) receptors mediate excitatory inputs to rostral ventrolateral medulla pressor neurons from hypothalamus.

Angiotensin II type 1 (AT(1)) receptors are located on pressor neurons in the rostral ventrolateral medulla, and their activation results in an increase in arterial pressure. However, the normal role of these AT(1) receptors in cardiovascular regulation is unknown. In this study, we tested the hypothesis that these receptors mediate synaptic excitation of rostral ventrolateral medullary pressor neurons in response to activation of the hypothalamic paraventricular nucleus. In anesthetized rats, microinjections of the gamma-aminobutyric acid receptor antagonist bicuculline were made into the paraventricular nucleus; this injection causes activation of the nucleus as a consequence of disinhibition. The pressor and sympathoexcitatory responses evoked by paraventricular nucleus activation were significantly reduced (by approximately 40% to 50%) after microinjection of the specific AT(1) receptor antagonists losartan or L-158,809 into the rostral ventrolateral medulla on the ipsilateral, but not contralateral, side. These responses were reduced to a similar degree after microinjections of the neuroinhibitory compound muscimol into the ipsilateral, but not contralateral, rostral ventrolateral medulla. However, bilateral microinjections of the glutamate receptor antagonist kynurenic acid into the rostral ventrolateral medulla had no effect on the responses evoked from the paraventricular nucleus. Conversely, bilateral microinjections of kynurenic acid into the rostral ventrolateral medulla virtually abolished the somatosympathoexcitatory reflex, whereas bilateral microinjections of losartan or L-158,809 had no effect on this reflex. The results indicate that excitatory synaptic inputs to pressor neurons in the rostral ventrolateral medulla arising from activation of the paraventricular nucleus are mediated predominantly by AT(1) receptors.

Interleukin-6 is a needed proinflammatory cytokine in the prolonged neural activity and transcriptional activation of corticotropin-releasing factor during endotoxemia.

Interleukin-6 (IL-6) is a proinflammatory cytokine that plays multiple roles in the central nervous system during infections and injuries. Although this molecule is capable of stimulating the release of ACTH and glucocorticoids, it has been demonstrated that a single injection of IL-6 fails to activate the paraventricular nucleus (PVN) neurons that control the hypothalamic-pituitary-adrenal axis. The observation that IL-6 receptor (IL-6R) is up-regulated in the brain during endotoxemia led us to hypothesize that prior induction of IL-6R synthesis could amplify the effect of circulating IL-6 on the neuroendocrine response. Rats received a first iv injection of either bacterial lipopolysaccharide (LPS; 5 microg) or vehicle solution. After a 6-h waiting period, they received a second iv injection of either recombinant rat IL-6 or vehicle solution and were killed 1 h thereafter. Using in situ hybridization, we observed that IL-6R was barely expressed in the PVN under basal conditions, but was rapidly produced in response to LPS. IL-6 itself was also able to induce the synthesis of its own receptor along cerebral blood vessels, and this effect extended to several parenchymal structures, including the PVN, when the cytokine was administrated after LPS. In agreement with our hypothesis, we found that IL-6 injected in LPS-pretreated rats stimulated PVN neurons, as revealed by the expression of CRF primary transcript and c-fos messenger RNA, an immediate early gene used as a marker of cellular activation. A significant increase in plasma corticosterone levels was also found in animals that received iv IL-6 injection after being pretreated 6 h before with the very low dose of LPS. The fact that IL-6 alone or injected after LPS treatment was unable to induce cyclooxygenase-2 synthesis is an argument in favor of a PG-independent mechanism. The relative contribution of IL-6 in stimulating CRF expression in the PVN and neural activity throughout the brain during endotoxemia was also investigated in IL-6-deficient mice after an ip injection of LPS. The endotoxin induced similar c-fos and CRF expression patterns in knockout and wild-type mice, but the expression levels were generally higher and/or lasted longer in wild-type animals. Taken together, physiological changes that may include the induction of IL-6R synthesis seem to be necessary for IL-6 to activate PVN neurons. Moreover, although IL-6 does not appear essential during the early phases of endotoxemia, this cytokine is required during the later phases to prolong the activation of neural cells throughout the brain and to maintain CRF expression in the PVN neurons that control the hypothalamic-pituitary-adrenal axis.

Stimulation of the paraventricular nucleus modulates firing of neurons in the nucleus of the solitary tract.

The present study assessed whether the baroreflex inhibition elicited by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) involves altered activity in the nucleus of the solitary tract (NTS). Unit recordings were made from 107 neurons in the NTS in anesthetized rabbits. Intravenous phenylephrine was used to induce a pressor response and to activate baroreflexes. Of the neurons that responded to pressor responses, two-thirds were excited and one-third was inhibited. Stimulation of the PVN inhibited 70% of the phenylephrine-responsive NTS neurons, with or without concurrent baroreceptor stimulation. When PVN stimulation was delivered concurrently with phenylephrine injection, more NTS neuronal inhibition and less excitation occurred than with phenylephrine alone. Usually PVN stimulation inhibited NTS neurons that were excited by pressor responses; less commonly, PVN stimulation excited NTS neurons that were inhibited by pressor responses. The findings are consistent with the view that PVN activation during the defense reaction inhibits baroreflexes by altering firing of NTS neurons.

Chronic activation of brain areas by high-sodium diet in Dahl salt-sensitive rats.

To map changes in neuronal activity in the brains of Dahl salt-sensitive (Dahl S) vs. salt-resistant (Dahl R) rats by high-sodium diet, we used immunohistochemical detection of Fra-like proteins as a marker for long-term neuronal activation. Compared with Dahl R rats during regular sodium intake, Dahl S rats showed modestly higher expression of Fra-like immunoreactivity (Fra-LI) in the supraoptic nucleus, anterior hypothalamic area (AHA), central gray, and nucleus of solitary tract (NTS) at 5,6, and 9 wk of age but clearly elevated Fra-LI in the magnocellular part of the paraventricular nucleus (PVN) at 6 wk of age (but not at 5 and 9 wk). In the median preoptic nucleus (MnPO) Fra-LI was lower at 9 wk of age and no differences were observed in the parvocellular PVN and subfornical organ in Dahl S vs. Dahl R rats on regular sodium intake. Compared with Dahl S rats on a regular-sodium diet, Dahl S rats on a high-sodium diet from 4 to 9 wk of age had significantly increased blood pressure and experienced transient activation of magnocellular PVN and MnPO and virtually no changes in the activity of the parvocellular PVN, AHA, and NTS. In contrast, Dahl R rats showed marked activation in the magnocellular PVN after 1 and 2 wk on a high-sodium diet compared with Dahl R rats on a regular-sodium diet. The present study demonstrates that Dahl S rats show differential activation of brain areas participating in regulation of osmotic and cardiovascular homeostasis during development of sodium-sensitive hypertension.

Nitric oxide regulates NMDA-driven GABAergic inputs to type I neurones of the rat paraventricular nucleus.

1. Whole-cell recordings were obtained from type I paraventricular nucleus (PVN) neurones in coronal slices of rat hypothalamus to study the involvement of nitric oxide (NO) in the modulation of inhibitory transmission resulting from the activation of N-methyl-D-aspartate (NMDA) receptors by the high affinity receptor agonist D,L-tetrazol-5-ylglycine. 2. A brief pulse of NMDA agonist (0.1-10 microM) faithfully elicited increases in action potential firing frequency in all type I cells tested (n = 55). In cells with membrane potentials positive to -75 mV, this excitation was accompanied by an underlying depolarization (> 2 mV) in the majority of cases (n = 45). At membrane potentials negative to -75 mV, NMDA agonist application elicited an initial monotonie depolarization, which was auxiliary to profound, rhythmic oscillations of the membrane potential, resulting in the emergence of burst-like activity in these cells (n = 8). 3. In addition to depolarizing the neurones, the NMDA agonist also elicited inhibitory postsynaptic potentials (IPSPs) in 40% (n = 22) of the cells tested. The IPSPs were inhibited by the GABAA receptor antagonist bicuculline methiodide (BMI). 4. Microdialysis of NO into the PVN has been shown to increase local levels of inhibitory neurotransmitters, including GABA. The possibility that NO-induced increases in GABA lead to an increase in inhibitory synaptic activity in PVN was investigated by administering NO by three different methods. Bath application of the donor compound, S-nitroso-N-acetyl-penicillamine (SNAP; n = 7), bubbled NO solution (n = 5), or the NO precursor L-arginine (n = 6) all elicited increases in IPSP frequency. 5. Production of NO in other brain centres has been linked to the activation of the NMDA receptor. In order to determine whether the increase in IPSPs following NMDA was the result of activation of NO, the production of NO was blocked with the NO synthase inhibitor N omega-nitro-L-arginine methylester (L-NAME). Subsequent NMDA receptor activation elicited more pronounced depolarizations, but there was no accompanying increase in IPSP frequency (n = 5). 6. This study demonstrates that GABAergic inhibition resulting from NMDA receptor activation can be regulated profoundly by NO. By increasing inhibitory transmission within a nucleus, NO may serve as an important intermediary in the regulation of neuronal excitability in the central nervous system.

Hypothalamo-Pituitary-Adrenocortical Regulation Following Lesions of the Central Nucleus of the Amygdala

Previous reports indicate that the central nucleus of the amygdala (CeA) stimulates adreno-corticotropin and corticosterone secretion, suggesting a role for this region in central hypothalamo-pituitary-adrenocortical (HPA) stress regulation. To evaluate this hypothesis, this study assessed the impact of CeA lesion on the response of hypophysiotrophic paraventricular nucleus (PVN) neurons to acute restraint and chronic unpredictable stress exposure. In contrast to previous reports, CeA lesions did not affect corticosterone or ACTH secretion induced by acute stress. Acute restraint increased PVN corticotropin releasing hormone (CRH) mRNA expression, increased the number of parvocellular PVN neurons expressing the co-secretagogue arginine vasopressin (AVP), and induced cFOS mRNA expression in the parvocellular PVN. However, there was no additional effect of CeA lesion on any measure of PVN activation. Chronic unpredictable stress exposure induced long-term activation of the HPA axis, noted by thymic involution, adrenal hypertrophy and increased PVN CRH mRNA expression. Stress-induced changes in thymus and adrenal weights were not affected by CeA lesion. Further, CeA lesion rats did not differ from controls in post-stress CRH mRNA expression. However, basal CRH mRNA expression was increased in the PVN of CeA rats, suggesting that the CeA plays a role in long-term inhibition of the PVN. The results of these studies are not consistent with the hypothesis that the CeA is necessary for stress-induced pituitary-adrenocortical activation. Rather, this region may play a stressor-specific modulatory role in regulation of HPA function.

615 Actions of acidic fibroblast growth factor on plasma corticosterone and neuronal activity of paraventricular nucleus in rats

615 Actions of acidic fibroblast growth factor on plasma corticosterone and neuronal activity of paraventricular nucleus in rats

Effects of various stressors on in vivo norepinephrine release in the hypothalamic paraventricular nucleus and on the pituitary-adrenocortical axis.

The hypothalamic-pituitary adrenocortical (HPA) system and sympathoneural and adrenomedullary systems are major effector systems that serve to maintain homeostasis during stress. Corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) of the hypothalamus, a determinant of both HPA and autonomic responses to stress, is under the control of many neurotransmitters and neuropeptides. Norepinephrine (NE) potently stimulates CRH neurons in the PVN; however, the physiologic role of NE in stress-induced activation of the HPA is unknown. In the present study we exposed animals to various stressors (immobilization (IMMO), cold (COLD), hemorrhage (HEM), hypoglycemia elicited by insulin administration (INS), pain and tissue damage caused by formalin injection (FORM) and sc injection of physiological saline (SAL), all of which are known to activate the HPA axis. Injection of physiological saline iv was used as a control. In vivo microdialysis was used to assess stressor- and intensity-specific activation of the PVN noradrenergic system, based on measurements of NE, its intraneuronal metabolite dihydroxyphenylglycol (DHPG), and the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC). Simultaneously with microdialysate collections, blood samples were obtained via catheters in the femoral artery to measure plasma ACTH and corticosterone (CORT) levels as dependent measures, to assess stress-induced activation of the HPA axis. At their highest intensities, all the stressors significantly increased levels of PVN microdialysate NE, DHPG, and DOPAC, and plasma ACTH and CORT. PVN NE levels varied across stressors, with IMMO and FORM more potent than INS, COLD, or HEM. INS and HEM evoked proportionately larger plasma ACTH responses than did IMMO, FORM, and COLD. Plasma CORT responses were largest during IMMO, FORM, and HEM. Except for COLD and HEM, there was a strong correlation of plasma ACTH levels with levels of NE, DHPG, and DOPAC in PVN microdialysate. The data suggest that, except for COLD or HEM, there is a strong positive correlation of PVN noradrenergic activation and activity of the HPA axis. With stressors such as IMMO and FORM, NE synthesis, reflected by DOPAC changes, is strongly positively correlated with activity of the HPA axis. Furthermore, the results indicate substantial stressor specificity of PVN catecholaminergic and of HPA responses to different stressors and are inconsistent with a founding tenet of Selye's stress theory, the doctrine of nonspecificity, which defines stress as the nonspecific response of the body to any demand.

Neural discharge can be modulated by carotid arterial injection of gastrin-17 in rat hypothalamic paraventricular nucleus.

Neural discharge in the hypothalamic paraventricular nucleus (PVN) was examined after gastrin-17 injection into the carotid artery in anesthetized rats. Neural discharge was increased by gastrin-17 injection into the carotid artery close to the cranium, and the response due to the gastrin was dose-dependent. No discharge response was seen when gastrin was injected into the jugular vein. These results suggest that gastrin circulating in the arterial blood can penetrate the blood brain barrier, and modulate neural PVN activity which is responsible for gastric acid secretion.

Regional suppression by lesions in the anterior third ventricle of c-fos expression induced by either angiotensin II or hypertonic saline.

Angiotensin II (250 pmol) infused into the cerebral ventricles of male rats induces the expression of c-fos in the subfornical organ, supraoptic and paraventricular nuclei of the hypothalamus, as well as in the lateral parabrachial nucleus, locus coeruleus and the nucleus of the solitary tract in the brainstem. Electrolytic lesions of the anteroventral third ventricle, principally the subcommissural (ventral) median preoptic nucleus, inhibited the dipsogenic response to i.c.v. angiotensin II and also suppressed c-fos expression in supraoptic nucleus, paraventricular nucleus, lateral parabrachial nucleus, locus coeruleus and nucleus of the solitary tract but not in the subfornical organ or dorsal median preoptic nucleus. The stimulating effect of i.c.v. angiotensin II on corticosterone was also reduced. Median preoptic nucleus lesions also suppressed the expression of c-fos following i.v. infusions of 6 micrograms angiotensin II in supraoptic nucleus and paraventricular nucleus but not in subfornical organ, dorsal median preoptic nucleus, lateral parabrachial nucleus, locus coeruleus and nucleus of the solitary tract. Median preoptic nucleus lesions reduced the dipsogenic effects of an intragastric infusion of hypertonic (1.5 M) saline and suppressed c-fos expression in supraoptic nucleus and paraventricular nucleus compared to sham-lesioned rats. However, c-fos expression was unaltered in subfornical organ, dorsal median preoptic nucleus lesions had no effect on the increased corticosterone induced by hypertonic saline. Subfornical organ lesions did not alter dipsogenic responses to i.c.v. angiotensin II, nor was the i.c.v. angiotensin II-induced expression of c-fos suppressed in the basal forebrain. These experiments show that the ventral median preoptic nucleus (but not the subfornical organ), part of the anteroventral third ventricle, is critical for the expression of c-fos in more caudal areas of the brain following i.c.v. angiotensin II. c-fos expression in supraoptic nucleus and paraventricular nucleus following i.v. angiotensin II is also dependent on an intact median preoptic nucleus, suggesting that supraoptic nucleus and paraventricular nucleus activation may be dependent on the median preoptic nucleus, and that suppression following i.c.v. infusions is not due to mechanical obstruction to infused peptide. However, there is a clear separation of the effects of i.c.v. and i.v. angiotensin II on brainstem structures. The median preoptic nucleus (but not the subfornical organ) seems essential for activation following the former but not the latter, suggesting alternative mechanisms for the effect of i.v. angiotension II on the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

Stress-induced activation of CRF and c- fos mRNAs in the paraventricular nucleus are not affected by serotonin depletion

The role of serotonin in regulating the stress response is controversial. We have investigated the effects of serotonin depletion by p-chlorophenylalanine (PCPA) on corticotrophin-releasing factor (CRF) mRNA and c- fos mRNA responses in the paraventricular nucleus (PVN) together with circulating levels of ACTH and corticosterone to both physical and psychological stressors in the rat. PCPA pretreatment, which resulted in a 95% depletion in hypothalamic serotonin, had no effect on basal levels of ACTH or the increase in response to the physical stress of hypertonic saline. Plasma ACTH concentrations were also not affected by serotonin depletion in response to the predominantly psychological stress of restraint. Both basal and restraint stress-induced circulating corticosterone levels were however further stimulated in the PCPA-pretreated rats suggesting a possible inhibitory serotoninergic tone at the adrenal level. C- fos mRNA was undetectable in control animals. Activation of c- fos mRNA in response to stress was unaffected by serotonin depletion and the activation of magnocellular PVN and supraoptic nucleus cells was demonstrated to be stressor dependent. Basal and stress-induced levels of CRF mRNA were unaffected by PCPA pretreatment. It appears therefore that under these experimental conditions there is little if any involvement of serotonin in either basal levels or the stress-induced activation of the hypothalamo-pituitary-adrenal axis in vivo.

Catecholaminergic projections to tuberoinfundibular neurones of the paraventricular nucleus: I. Effects of stimulation of A1, A2, A6 and C2 cell groups

Extracellular electrical activity was recorded from 203 paraventricular nucleus (PVN) neurones antidromically identified as projecting to the median eminence. Spontaneous activity and the effects of stimulation of the A1, A2, A6 and C2 catecholaminergic cell groups upon the PVN neurones were examined. Cells were located at a mean height 2.29 ± 0.03 mm above the base of the brain, corresponding with the corticotropin-releasing factor (CRF) rich component of the nucleus. The mean firing rate was 3.2±0.3 Hz and antidromic invasion latency was 9.9±0.3 msec. Seventy-six % of cells tested were activated by painful somatosensory stimuli. Electrical stimulation of the A1 or A2 region evoked excitatory responses from the majority of cells tested (76% and 85%, respectively), whilst stimulation of the A6 and C2 regions evoked more inhibitory responses (43% and 59%, respectively). Most responses (56%), whether excitatory or inhibitory, were not clearly defined in terms of latency, and were only observed following delivery of 5–10 single shocks at 0.5 Hz. Excitation recorded following A1 and A2 stimulation suggests a facilitatory role for noradrenaline in the regulation of PVN activity. Inhibitory responses following C2 stimulation indicate that adrenaline may serve to inhibit such activity, whilst the more mixed responses following A6 stimulation suggest that the projections of this region differ in some way from those of the A1 and A2 cells. Response reversals were observed, after delivery of higher frequency stimulation, for a substantial proportion (20%) of the cells tested.

Decreased hexokinase activity in paraventricular nucleus of adult SHR and renal hypertensive rats.

Metabolic activity was assessed in the brains of spontaneously hypertensive rats (SHR) using the histochemical hexokinase (HK) technique and photodensitometric analysis. Of eight regions known to play a role in cardiovascular regulation, only the paraventricular nucleus of the hypothalamus (PVH) exhibited alterations in HK activity. Significantly lower levels of HK activity in SHR than in control Sprague-Dawley and Wistar-Kyoto rats were measured in both the parvo- and magnocellular divisions of the PVH. No differences in HK activity were found in the anterior hypothalamic nucleus, posterior hypothalamic nucleus, supraoptic nucleus, subfornical organ, central nucleus of the amygdala, or the medial nucleus of the tractus solitarius of SHR. Similar results were obtained in renal hypertensive rats; furthermore, a positive correlation was found between levels of arterial pressure and densitometric readings. These latter results strongly suggest that metabolic alterations in the PVH of SHR are directly related to the increases in arterial pressure and are not due to the genetic makeup of SHR. In light of studies by others, the data from the present study have been interpreted to suggest that the decreases in metabolic activity in the PVH of the adult SHR are the result of a central attempt to bring the level of the arterial pressure down to normal levels and not to the altered activity of a region that might be acting to keep arterial pressure elevated.

Inhibitory effects of 2-deoxytetronic acid, a putative endogenous satiety factor, on paraventricular neurons of rats, in vitro

The endogenous sugar acid, 2-deoxytetronic acid (2-DTA) was investigated for its effects on activity of paraventricular nucleus (PVN) neurons in slice preparations from rats. 2-DTA dose-responsively inhibited the spontaneous activity of 23 of the 53 PVN neurons tested at concentrations of 10 −5 to 10 −2 M, and 2 were excited. The inhibitory responses were not due to osmotic changes by 2-DTA administration. The high concentration of 2-DTA needed to produce responses suggests that it acts as substrate for oxidative metabolism rather than as a neurotransmitter or neuromodulator in the suppression of feeding behavior.

Absence of a prostaglandinic mediator in the lateral hypothalamic cardio-vascular inhibition.

The cardio-vascular inhibition elicited by electrical stimulation of the paraventricular nucleus in the lateral hypothalamus of anaesthesized and desafferentiated dogs is not linked with a mediator release like PGE. The effect of this biological agent is not registered in the isolated femoral artery of a receiver, after deviation by a cruised circulation of the arterial blood of a hypothalamic stimulated donor dog. Antipyretics, which are also prostaglandin-synthetase inhibitors, enhance the lateral hypothalamic reactions. As the thermoregulation centre is localized in the same region as the cardio-vascular inhibition centre and because lowering of temperature depends upon vasodilation and decrease in the general cellular metabolism, both functions of the paraventricular nucleus activity, a hypothesis is proposed that thermoregulation and cardio-vascular inhibition centres are a functional and anatomical unity.

Unit activity in the paraventricular nucleus of female rats at different stages of the reproductive cycle and after ovariectomy, with or without oestrogen or progesterone treatment.

SUMMARY Spontaneous firing rates were determined from extracellular recordings made from 878 antidromically identified units in the paraventricular nucleus (PVN) during the reproductive cycle of the female rat and in analytical experiments. In the latter, rats were ovariectomized and subsequently received either no treatment or oestrogen and/or progesterone. Among rats at metoestrus, dioestrus, mid-pregnancy and in ovariectomized progesterone-treated groups there was no significant difference in the firing rates. However, they were significantly lower than the rates recorded during pro-oestrus, oestrus, full-term pregnancy, the day of parturition, during lactation and in ovariectomized, oestrogen-treated rats. In spayed rats the mean firing rate was significantly lower than at pro-oestrus, oestrus, fullterm pregnancy, the 24 h period after parturition, during lactation and after oestrogen treatment. When progesterone was given subcutaneously to oestrogenized rats, the PVN activity, increased by oestrogen, was significantly depressed 4 h after administration. By 8 h the firing rate had completely recovered. The frequency distribution of the firing rates in pro-oestrus and oestrus showed an approximately normal distribution while those in metoestrus and dioestrus and mid-pregnancy had a Poisson distribution. At full term there were two peaks: one in the range of 3–5 spikes/s and the other less than one spike/s. The distribution was approximately normal on the day of parturition and subsequently the pattern became irregular. In ovariectomized rats and those treated with progesterone it was of a Poisson type while there was a distinct shift to higher frequencies after oestrogen treatment. The mean absolute refractory period, measured for each unit, varied and appears to be dependent on hormonal conditions. It was short in oestrus and long in dioestrus and mid-pregnancy. Oestrogen treatment significantly shortened the absolute refractory period of ovariectomized rats.