Ventromedial Hypothalamic Neurons Research Articles

Projections of oestrogen-sensitive neurones from the ventromedial hypothalamic nucleus of the female rat.

Stimulation of the mesencephalic central grey matter caused antidromic activation of 199 neurones in the hypothalamic ventromedial nucleus of forty-six urethane-anaesthetized female rats, of which twenty-two (ten ovariectomized and twelve ovariectomized and oestrogen treated) had the lateral projection of the nucleus disrupted by a small parasagittal knife-cut. The remaining twenty-four rats (ten ovariectomized and fourteen ovariectomized and oestrogen treated) had a cut in the frontal plane to interrupt caudal projection of the nucleus. In eight animals with the lateral knife-cut, eighteen cells were antidromically activated from the central grey matter as well as from the dorsal longitudinal fascicle. Collision between the potentials activated from these two sites revealed that seventeen of them descended to the central grey matter by way of the periventricular system, one cell having a bifurcated axon to these sites. Likewise, eleven cells in another group of eight animals with the posterior cut were found to project to the central grey matter via the perifornical region. Pre-treatment with oestrogen significantly lowered the activation thresholds and absolute refractory periods of neurones antidromically stimulated from the central grey in ovariectomized animals bearing posterior but not lateral knife-cuts. These results suggest that the ventromedial hypothalamic neurones responsible for oestrogen-dependent autonomic and behavioural functions project to the central grey via a lateral rather than a posterior pathway.

The pattern of ventromedial hypothalamic neuron activity in freely moving rat

The pattern of ventromedial hypothalamic neuron activity in freely moving rat

Different paths are taken by midbrain projections of two classes of ventromedial hypothalamic neurons with different cell sizes

Different paths are taken by midbrain projections of two classes of ventromedial hypothalamic neurons with different cell sizes

Direct effects of 2-DTA, 3-DPA and estrogen on the membrane excitability of guinea-pig ventromedial hypothalamic neurons

Direct effects of 2-DTA, 3-DPA and estrogen on the membrane excitability of guinea-pig ventromedial hypothalamic neurons

Hyperprolactinemia: its electrophysiologic and pharmacologic effect on neurons of the ventromedial nucleus of the hypothalamus

Extracellular action potentials were recorded from 691 neurons in the ventromedial hypothalamus (VMH) of urethane anesthetized female rats under acute and chronic sham-operated and hyperprolactinemic conditions. Hyperprolactinemia was produced by transplanting pituitaries under the kidney capsules. Neuronal excitability was recorded and analyzed during spontaneous, baseline activity and following the iontophoretic application of prolactin, dopamine (DA) and luteinizing hormone-releasing hormone (LH-RH). No statistically significant changes were observed in the spontaneous electrical activity of VMH neurons under the conditions tested. Of the responsive neurons, approximately 90% of the neurons recorded and tested with prolactin displayed an increase in firing activity while DA produced a decrease, independent of the endogenous plasma prolactin levels (basal or elevated). However, the response to LH-RH was modified in the chronic hyperprolactinemic animal. The predominant response of VMH neurons to LH-RH in acute sham-operated and hyperprolactinemic as well as in chronic sham-operated animals was one of inhibition, while in the chronic hyperprolactinemic animal, the application of LH-RH initiated excitation rather than inhibition. These results provide evidence that chronic (long-term) exposure to elevated prolactin levels is a sufficient stimulus to modify the neuronal response pattern of VMH nerve cells to iontophoretically applied LH-RH but not to prolactin nor to DA.

Early estrogen‐induced nuclear changes in rat hypothalamic ventromedial neurons: An ultrastructural and morphometric analysis

Alterations in the fine structure of nuclei of ventromedial hypothalamic neurons in ovariectomized (OVX) rats after either a 2-hour exposure to estradiol (E2) or a discontinuous exposure (2 hours E2/7 hours off/2 hours E2), previously shown sufficient for female rat sexual behavior (Parsons et al., '82a), were examined with the electron microscope. Morphometric measurements of nucleolar, nuclear, and somal areas, and nuclear shape and perimeter were accomplished at the light microscope level. After 2 hours of E2, the appearance of the nucleoplasm was altered, with a decrease in the small, scattered clumps of heterochromatin. Nuclear shape appeared dramatically altered from nonspherical, invaginated profiles toward spherical, smooth profiles. Nucleolar, nuclear, and somal hypertrophy were evident. In addition, stacked rough endoplasmic reticulum was present more frequently in E2-treated than control OVX neurons. After the discontinuous (2 hours/7 hours/2 hours) E2 treatment, progressive loss of small clumps of heterochromatin along the nuclear envelope as well as in the nucleoplasm had occurred. Decrease in a large heterochromatin clump along the nuclear envelope was correlated with an increase in nucleolus-associated chromatin. As determined by a distribution analysis, these estrogen-induced nuclear changes co-occurred more frequently than predicted from mutual independence. These findings, the marked co-occurrence of E2-induced changes in 30% or more of the cells, and the differences between the 2-hour E2 and the 2-hour/7-hour/2-hour group are consistent with a cascade of cell nuclear changes in the first few hours after estrogen onset.

Inhibition of the lordosis reflex in rats by intrahypothalamic infusion of neural excitatory agents: Evidence that the hypothalamus contains separate inhibitory and facilitatory elements

In attempts to activate lordosis-facilitating neural mechanisms in the ventromedial hypothalamus (VMH), neural excitatory agents were infused into the medial hypothalamus, and the effects of the infusions on the lordosis reflex and on the electrical activity of VMH neurons were studied. Surprisingly, bilateral intrahypothalamic infusion of glutamate (10 mM, 1.0 μl/side) into behaving, ovariectomized, estrogen-treated rats displaying moderate lordotic responsiveness did not facilitate lordosis, but instead, resulted in a rapid (within a few minutes) and transient (recovery in about 20 min) inhibition of lordosis. Further experiments showed that this lordosis-inhibiting effect of glutamate was dose-related, and was completely blocked by prior infusion of a local anesthetic, procaine. Infusion of KCl (1.5 or 15%, 1.0 μl/side) also induced a dose-related, rapid and transient inhibition of lordosis, that was essentially identical to that induced by glutamate. Kainic acid (0.25 μg/0.5 μl/side) also caused a rapid inhibition of lordosis, but the effect was long-lasting (days). The inhibition of lordosis by these agents was dissociated in time course, presence, and/or severity from effects on non-lordotic behaviors. Electrophysiological studies showed that all three agents tested could excite multiunit activity of the VMH, and that the time courses of these excitations were closely comparable to those of the inhibition of lordosis induced by the respective agents. Altogether, these studies indicated that the excitation of certain medial hypothalamic neurons can inhibit the lordosis reflex. The implied lordosis-inhibiting neural mechanisms are separate from facilitatory mechanism(s), according to differences in latency, duration, and procaine-sensitivity of response.

Direct action of mazindol on guinea-pig ventromedial hypothalamic neurons: Intracellular studies in slice preparation

Neuronal responses in the ventromedial hypothalamic nucleus (VMH) to mazindol (MZD) were examined by intracellular recordings in hypothalamic slices in vitro. Bath application of MZD caused depolarization of the membrane by 8.0±3.4 mV (mean±S.D.) associated with an increase in the input membrane resistance (23.0±5.8%) among 20% of the cells examined. Current-voltage plots, obtained simultaneously, showed the reversal potential between −80 and −90 mV. These results indicate that MZD depolarizes VMH neurons by reducing the K + conductance, through a mechanism similar to that of glucose, and the anorectic action of MZD can be explained by its direct effects on the VMH.

Brain region specificity in estradiol effects on neuronal ultrastructure in rats

The effects of long-term (15 days) and short-term (3 days) treatment with estradiol benzoate (EB) on stacking of rough endoplasmic reticulum in neurons of four brain regions (medial preoptic nucleus, ventromedial hypothalamus, arcuate nucleus and midbrain central gray) were investigated. These regions were chosen for their role in reproduction in female rats and/or the presence of estradiol-concentrating cells. Long-term EB treatment increased the proportion of neurons in the ventromedial hypothalamus (by 30%) and medial preoptic nucleus (by 17%) that contained stacks of rough endoplasmic reticulum. Short-term EB affected stacking only in ventromedial hypothalamic neurons. EB was without effect on neurons of the arcuate nucleus of the hypothalamus or midbrain central gray. The degree of stacking of rough endoplasmic reticulum in neurons of the ventromedial hypothalamus was positively related to the level of sexual behavior (lordosis) activated by these hormone treatments.

Microiontophoretic application of morphine and naloxone to neurons in hypothalamus of rat

The present experiments used urethane-anesthetized rats and single cell recording to study the electrophysiological properties of ventromedial hypothalamic (VMH) cells following different doses of morphine and naloxone, applied microiontophoretically. More than 45% of ventromedial hypothalamic units reacted in a dose-response fashion to local application of morphine. In the majority of the ventromedial hypothalamic neurons, naloxone failed to reverse the effects of morphine. Naloxone alone had effects on 37% of the ventromedial hypothalamic units. The ventromedial hypothalamic units exhibited different response patterns from those observed from other CNS sites in response to the microiontophoretic application of morphine and naloxone; this difference is discussed. The present neurophysiological findings support the existence of opiate target sites with multiple opiate receptors within the ventromedial hypothalamus.

Food intake control and RNA content of hypothalamic neurons in infant rats

The influence of glycerol, glucose and lysine administration on the total RNA content in individual neurons of the ventromedial hypothalamus (VMH) and lateral hypothalamus area (LHA) in infant male rats was studied. Sixty minutes after administration, the total RNA content of the VMH neurons significantly decreased—from 13th day after glycerol and from 17th day after the glucose and lysine administration. The total RNA content of LHA neurons significantly increased from 17th day after glycerol and glucose and on 25th day after lysine administration. The noted changes of the RNA content, and especially the changes of the RNA proportion in these hypothalamic regions are well corresponding with the onset of the hypophagic effect of glycerol, glucose and amino acids in infant rats. The oppositional changes of the RNA content of VMH and LHA neurons are in conformity with the different role of these hypothalamic centers in food intake control.

Temporal pattern of HRP spread from an iontophoretic deposit site and description of a new HRP-gel implant method.

In the course of examining afferents to ventromedial hypothalamic (VMH) neurons using horseradish peroxidase (HRP), we needed to know how close to an iontophoretic deposit site neurons could be proved to be retrogradely labeled. In evaluating cells near but clearly outside HRP deposit sites visualized after a 24-hour survival period, for example, neurons which had been filled with HRP by somal or dendritic uptake could not be treated as retrogradely labeled and thus would not add to studies of intrahypothalamic connections. Rats were given standardized iontophoretic applications of HRP into VMH (continuous positive current 0.25 mu amp for 1 minute) and sacrificed after 5 or 15 minutes, 1, 4, 8, 12, or 24 hours in order to examine the pattern of HRP spread. The chromogen was tetramethylbenzidine. The volume of the application site visualized at 24 hours was less than 10% of maximum site size, which occurred at 1 hour. Since the cells located within the maximal spread boundary are candidates for nonretrograde labeling, HRP data on local connections obtained even from small iontophoretic deposits must be evaluated in the light of the demonstrated expansion and subsequent contraction of the application site. These results may also hold implications for the precision with which distant connections can be examined using the HRP retrograde method, as sites that appear discrete when visualized after 24-hour survival may have overlapped at shorter times post-iontophoresis. Incorporation of retrograde tracers into polyacrylamide gels provides an effective alternative to pressure injection or iontophoresis of aqueous tracer solutions. We describe a method for filling micropipettes with HRP-polyacrylamide gel. The pipettes are then implanted into brain sites to provide a confined pool of HRP. With postimplantation survival of 24 hour or longer, this method produces sites comparable in size to iontophoretic sites examined at 24 hours and results in improved retrograde labeling. Some results obtained with this method concerning the afferent connections of the dorsomedial hypothalamus are described.

Evidence that two sizes of ventromedial hypothalamic neurones project to the mesencephalic central grey matter in rats.

The spatial spread of the extracellular antidromic action potentials was measured in eighty-three neurones in the ventromedial nucleus region of the female rat hypothalamus following electrical stimulation of the mesencephalic central grey matter. The positive-negative configuration of the antidromic action potentials across the extracellular field suggested that the potentials were generated predominantly by neuronal soma with simple geometries. When represented by the distance travelled by the electrode, at which peak-to-peak spike amplitude exceeded the half maximum value, the spatial spread of the extracellular field ranged from 25 to 174 micron. The frequency distribution for the field size was distinctively bimodal and could be divided into large and small groups at 85 micron. Antidromic action potentials with larger extracellular fields had significantly larger maximum spike amplitude and shorter duration, indicating that differences in field size were associated with neuronal size. At least 55% of the central grey projection of the ventromedial nucleus originated from small neurones. Taking into account the sampling bias, a much greater proportion of the central grey projection may arise from small neurones. The lack of a systematic difference in the antidromic spike latencies between large and small cells indicated that axonal thickness is not the major factor in determining the latency of the responses of the ventromedial hypothalamic neurones to stimulation of the central grey matter.

Response of glucose-responsive ventromedial hypothalamic neurons to scrotal and preoptic thermal stimulation in rats

Almost all ventromedial hypothalamic (VMH) neurons facilitated by electro-osmotic application of glucose responded to scrotal thermal stimulation. On the other hand, only 50% of neurons which did not respond to glucose responded to the thermal stimulation. The VMH neurons facilitated or inhibited by scrotal warming were mostly facilitated or inhibited by preoptic warming, respectively. These results suggest that thermal signals from scrotal skin and preoptic area were conveyed to VMH neurons, especially to glucose-responsive ones, and could influence feeding control.

Hormonal and chemical modulation of ventromedial hypothalamic neurons responsive to vaginocervical stimulation.

Neurons of the ventromedial hypothalamus (VMH) in female rats were electrophysiologically recorded via multibarrelled glass micropipettes and tested for responsiveness to vaginocervical stimulation as well as to a variety of other peripheral stimuli. A small percentage of VMH neurons were found to be specifically responsive to vaginocervical stimulation (type I response) in the ovariectomized animal. Priming the rats with estrogen (E) and progesterone (P) significantly increased the percentage of neurons responding specifically to vaginocervical stimulation but had no effect on the percentage of nonspecifically responding (type II) and nonresponding (type III) neurons. Pharmacological testing of all three types of VMH neurons was accomplished by iontophoretic application of luteinizing hormone releasing hormone (LHRH), prolactin (PRL), and dopamine (DA) to the cell membrane. PRL excited the majority of neurons tested and DA inhibited the majority of tested units regardless of the hormonal condition of the animal or the response elicited by vaginocervical and peripheral stimulation, LHRH, however, produced changes in firing rate which were related to the type of response evoked by vaginocervical stimulation. In E-P-primed animals, neurons which were specifically or nonspecifically affected by vaginocervical stimulation responded to LHRH in a similar manner whereas a different LHRH response profile was obtained in those neurons which were not effected by vaginocervical stimulation. The results indicate that an afferent pathway from the vaginocervix to the VMH exists, that E-P priming in some manner increases the probability that a VMH neuron will respond specifically to vaginocervical probing, and that the effect of LHRH is different in neurons responding to vaginocervical stimulation than in nonresponding neurons.

Dual effects of electrical stimulation of ventromedial hypothalamic neurons on gastric acid secretion in rats.

Effects of electrical stimulation of the ventromedial hypothalamus (VMH) on gastric acid output and mucosal blood flow were examined in rats anesthetized with urethan. With stimulation of this area, a significant increase in acid output and mucosal blood flow occurred in 8 out of 16 animals. In these eight rats, the tip of the electrode had been placed mainly within the caudal portion of VMH. When the basal acid output was maintained at a relatively high level by pretreating the rats with 2-deoxy-D-glucose, electrical stimulation of the VMH significantly reduced the levels of these gastric parameters in 9 out of 12 animals. In the remaining three animals, the tip of the electrode had been placed in an area outside the VMH. These findings suggest that VMH is not a homogeneous neuron group, and both excitatory and inhibitory neurons probably play a role in regulating gastric functions.

Action of prolactin, dopamine and LHRH on ventromedial hypothalamic neurons as a function of ovarian hormones.

The effect of iontophoretically-applied prolactin, dopamine, LHRH and LHRH-antagonist analog on the electrical activity of neurons (n = 192) located in the ventromedial nucleus of the hypothalamus (VMH) was studied in untreated and hormone-treated ovariectomized female rats (n = 63). The spontaneous electrical activity of VMH neurons was unaffected by the presence or absence of the ovarian hormones. Neuropharmacological studies indicate that the iontophoretic deposition of prolactin and dopamine produced opposing results, in that prolactin increased the electrical activity of the majority of the VMH neurons tested while dopamine decreased their activity. Finally, the application of LHRH and LHRH-antagonist analog to VMH neurons resulted in a marked suppression of their electrical activity that was even more pronounced in the presence of ovarian hormones. The present work provides evidence at the electrophysiological level of hormonal influences on the responsiveness of VMH neurons to LHRH and its antagonist analog, and demonstrates a relationship between the responsiveness of VMH neurons to prolactin and dopamine.

Properties of ventromedial hypothalamic neurons with axons to midbrain central gray.

In female rats anesthetized with urethane, 151 neurons in and around the ventromedial nucleus of the hypothalamus were identified by antidromic activation as having axonal projection to the mesencephalic central gray at the midcollicular level. Identified neurons were most numerous in the rostral part and at the borders of the nucleus.

A probable role for norepinephrine in feeding after hypothalamic injection of morphine

When morphine is instilled directly into the ventromedial hypothalamus of rats there is a latent period followed by a prolonged bout of feeding. This enhanced activity may be mediated by the release of norepinephrine; for morphine-induced feeding was depressed by the α-adrenergic receptor blocker phentolamine. Several neurotransmitter agonists and antagonists failed to duplicate this action: propranolol, serotinin, methysergide, apomorphine and haloperidol were ineffective in modifying ingestion elicited after morphine. Unlike apomorphine, dopamine augmented morphine's a feeding effect. This difference may exist because dopamine acts as a precursor for norepinephrine formation in local ventromedial hypothalamic neurons.

Effects of preoptic thermal stimulation on the ventromedial hypothalamic neurons in rats

The effects of temperature on food intake were observed on activities of 54 ventromedial hypothalamic neurons in rats in response to iontophoretically applied glucose and to preoptic thermal stimulation. The major response was that 16 neurons out of 22 facilitated by glucose in the satiety center were facilitated by a rise in preoptic temperature.