Acute thermoregulatory effects of unilateral electrolytic lesions of the medial and lateral preoptic area in rats

Unilateral anodal lesions of the medial or lateral preoptic area (POA) in unanesthetized rats had opposite thermoregulatory effects immediately after the lesions were made. Lesions of the medial POA evoked hyperthermias and accompanying cold defense responses, including vasoconstriction of the tail, increased oxygen consumption, shivering, and heat conservation postures. The hyperthermias had latencies of 0–30 minutes and reached maximum values within 120 minutes postlesion. They were independent of ambient temperature and dissociable from the hyperactivity often seen after such lesions. Damage to the lateroventral POA elicited acute falls in body temperature, as well as vasodilation of the tail, decreased oxygen consumption, inhibition of shivering in cool environments, and prone body extension. Unilateral cathodal lesions throughout the POA yielded only hyperthermia. These results suggest a possible anatomical segregation of heat and cold defense functions within the anterior basal forebrain.     

Electrical stimulation of forebrain structures and its effect on copulatory as well as stimulus-bound behavior in ovariectomized hormone-primed rats

Chronic bipolar electrodes were implanted into various forebrain structures in 45 ovariectomized hormone-treated female rats. A significant decrease in copulatory behavior as measured by the lordosis-to-mount ratio and an increase in the female's avoidance of sexual contact was observed following electrical stimulation of the olfactory bulbs, habenula region, caudate-putamen region and preoptic area. This decrease could not be attributed to motor effects nor aversive side effects of stimulation. On the other hand, anterior hypothalamic, premamillary and medial forebrain bundle stimulation resulted in no apparent change in mating behavior. Tests for self-stimulation in all forebrain sites revealed that only implants in the medial forebrain elicited positive responses.     

Observations on the thermoregulatory effects of preoptic warming in rats

Experimental warming of the preoptic-anterior hypothalamic area was used to evaluate behavioral and autonomic thermoregulatory heat-loss responses. Hypothalamic warming was associated with reduced behavioral heat intake and decreased core and peripheral temperatures in rats working for radiant heat reward in a cold environment. Baseline rates of responding for external heat were determined by ambient temperature, but the magnitude of changes in core or peripheral temperatures during preoptic warming were not. Behavioral responses compensated for variations in ambient temperature so that the threshold hypothalamic temperature above which heat loss was activated by preoptic warming was not altered by changing ambient temperatures. Heat loss during hypothalamic warming was a function of both autonomic and behavioral thermoregulatory responses because the decrease in body heat content during preoptic warming could not be accounted for by the decreased behavioral heat intake alone. The threshold hypothalamic temperature for elicitation of tail vasodilation decreased systematically as ambient temperature increased when no behavioral option was available. In the rat, both behavioral and autonomic thermoregulatory responses cooperate to determine the magnitude of heat loss which is proportional to the magnitude of preoptic warming.     

Multiple connections of medial hypothalamic neurons in the rat

Summary The responses of 700 single neurons in the hypothalamus to electrical stimulation of the preoptic area, limbic structures, and midbrain were studied to determine the location of neurons with multiple inputs and to identify by antidromic activation the projection areas of those neurons.Converging excitatory inputs, observed in 134 responsive hypothalamic neurons, were principally derived from the preoptic, limbic, and midbrain areas. Inputs from separate nuclei of the amygdala were noted in the response of individual hypothalamic neurons. Two classes of short latency transsynaptic responses to amygdala stimulation were defined, indicating either separate pathways from the amygdala to the medial hypothalamus or two types of fibers conducting at different velocities. Stimulation of single or multiple sites in the preoptic and limbic areas, as well as in the arcuate nucleus and medial forebrain bundle produced inhibition of hypothalamic neuronal activity.Most antidromically identified medial hypothalamic neurons projected to the preoptic area, median eminence (tuberoinfundibular neurons), or midbrain. Evidence is presented for collateral projections of tuberoinfundibular neurons to the preoptic area and reticular formation. Medial hypothalamic neurons received inputs from the preoptic area, lateral septal nucleus, amygdala, ventral hippocampus (subiculum), and fornix. These findings illustrate a pattern of reciprocal connections between the medial hypothalamus and limbic and midbrain structures.It was concluded that the hypothalamus contains a type of neuron that is equipped to perform complex integrations and to coordinate directly the behavior of neurons in a diversity of anatomical regions.Abbreviations ABL basolateral nucleus of the amygdala - ACO cotical nucleus of the amygdala - AHA anterior area of the hypothalamus - ARH arcuate nucleus of the hypothalamus - DMH dorsomedial nucleus of the hypothalamus - FX fornix - HPC ventral hippocampus (subiculum) - LS lateral septal nucleus - ME median eminence - MH medial hypothalamus - MFB medial forebrain bundle - MP posterior mamillary nucleus - PH posterior nucleus of the hypothalamus - PMD dorsal premamillary nucleus - PMV ventral premamillary nucleus - POA preoptic area - PVG periventricular gray - PVH paraventricular nucleus of the hypothalamus - RF reticular formation of the mesencephalon - RT reticular nucleus of the thalamus - SUM supramamillary nucleus - VMH ventromedial nucleus of the hypothalamus Performed with financial support from the National Institutes of Health (Grants NS 09688 and RR 00165)     

Regional differences in desensitization of c-Fos expression following repeated self-stimulation of the medial forebrain bundle in the rat

The acute self-stimulation of the medial forebrain bundle was reported to induce the expression of c-Fos, the protein product of c-fos, an immediate early gene, in the central nervous system. In the present study, we examined regional changes in c-Fos expression in several reward-related areas of rat brain in response to short- and long-term exposure to self-stimulation of the medial forebrain bundle. Short-term one-hour stimulation of the medial forebrain bundle for one day after training, which evoked steady self-stimulation behavior, significantly increased the number of c-Fos-positive neurons bilaterally in all of 15 brain structures assayed, as compared to the non-stimulation control. Among them, structures showing a larger number of the stained neurons on the stimulated side were the anterior olfactory nucleus, amygdala, medial caudate-putamen complex, lateral septum, bed nucleus of the stria terminals, ventral pallidum, substantia innominata, lateral preoptic area, medial preoptic area, lateral hypothalamus rostral to the stimulating electrodes, and substantia nigra. Long-term stimulation of the medial forebrain bundle once daily for five successive days, which maintained consistently stable self-stimulation behavior, also increased the number of c-Fos-positive neurons in the aforementioned structures, as compared to the control. However, the long-term rewarding stimulation diminished the increased number of labeled neurons, as compared to the short-term rewarding stimulation. Seven areas, medial caudate-putamen complex, ventral pallidum, substantia innominata, lateral preoptic area, medial preoptic area, rostral lateral hypothalamus and substantia nigra, showed asymmetrical, ipsilateral predominance after the short- and long-term stimulation. However, the stained neuron count in those areas after the long-term stimulation was reduced to less than 50% of that found after the short-term stimulation with the exception of lateral preoptic area and rostral lateral hypothalamus. The results suggest that the development of desensitization of c-Fos response may differ among the reward-relevant brain regions as a consequence of repeated self-stimulation. They also indicate that a larger portion of neurons in the lateral preoptic area and rostral lateral hypothalamus may be implicated in both short- and long-term self-stimulations of the medial forebrain bundle.     

Electrophysiological investigation of cortico-hypothalamic relations in cats

Projections of different parts of the orbito-frontal cortex, the basal temporal cortex, and the hippocampus on hypothalamic nuclei were studied by recording focal responses in acute experiments on cats anesthetized with pentobarbital and chloralose. The proreal gyrus was shown to have local projections in the latero-dorsal zones of the preoptic region, in the rostral parts of the medial forebrain bundle, and also in the region of the lateral and posterior hypothalamus with the mammillary bodies. The orbital gyrus projects mainly to the latero-dorsal portions of the forebrain bundle, the latero-ventral part of the preoptic region, and the region of the lateral and latero-dorsal hypothalamic nuclei; projections from the orbital gyrus are relatively diffuse in character. The basal temporal cortex has diffuse projections in the central part of the preoptic region, in the latero-ventral parts of the medial forebrain bundle, and in the lateral mammillary body. No marked foci of activity were found in the hypothalamic structures during hippocampal stimulation. Diffuse projections of the hippocampus were traced in the ventral part of the preoptic region and the ventral regions of the medial forebrain bundle, and also in the lateral hypothalamus and in the lateral mammillary nucleus.Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 358–365, July–August, 1976.     

Heat loss responses and blockade of prostaglandin E2-induced thermogenesis elicited by α1-adrenergic activation in the rostromedial preoptic area

The unilateral microinjection of noradrenaline (NA), but not vehicle solution, into the rostromedial preoptic area (POA) elicited simultaneous increases in cutaneous temperatures of the tail and sole of the foot and decreases in the whole-body O₂ consumption rate, heart rate, and colonic temperature in urethane–chloralose-anesthetized rats, suggesting a coordinate increase in heat loss and decrease in heat production. The magnitude of these responses increased dose-dependently over the range of 1–100 pmol, except for the metabolic and bradycardic responses. Similar hypothermic responses were elicited by the microinjection of 40 pmol methoxamine (an α₁-adrenergic agonist), but not by that of clonidine (an α₂-agonist) or isoproterenol (a β-agonist). Sites at which microinjection of NA elicited hypothermic responses were in the vicinity of the organum vasculosum of the lamina terminalis including the median preoptic nucleus, whereas no thermal or metabolic response was elicited when NA was microinjected into the lateral POA or caudal part of the medial POA. The microinjection of 130 fmol prostaglandin (PG) E₂ into the NA-sensitive site always elicited thermogenic, tachycardic, and hyperthermic responses. Furthermore, the PGE₂-induced febrile responses were greatly attenuated by prior administration of NA at the same site. These results demonstrate that NA in the rostromedial POA exerts α₁-adrenoceptor-mediated hypothermic effects and opposes PGE₂-induced fever.     

Medial preoptic connections with the midbrain tegmentum are essential for male sexual behavior

The medial preoptic area appears to play a major role in the control of sexual behavior. Efferents from the medial preoptic area course through the medial forebrain bundle to pass through and/or terminate in the dorsolateral and ventral tegmentum of the midbrain. Bilateral lesions of the dorsolateral tegmentum eliminate mating behavior in male rats, reproducing the effect of bilateral medial preoptic lesions. Sexual behavior is also eliminated when a preoptic lesion on one side of the brain is combined with a lesion of the dorsolateral tegmentum on the other side of the brain. In other words, asymmetric brain damage which bilaterally destroys the preoptic connections with the dorsolateral tegmentum eliminates male sexual behavior, and we conclude that the connections between these two regions are essential for copulation.     

The preoptic area in the hypothalamus is the source of the additional respiratory drive at raised body temperature in anaesthetised rats

In mammals that use the ventilatory system as the principal means of increasing heat loss, raising body temperature causes the adoption of a specialised breathing pattern known as panting and this is mediated by the thermoregulatory system in the preoptic area of the hypothalamus. In these species an additional respiratory drive is also present at raised body temperature, since breathing can reappear at low Pa,CO2 levels, when stimulation of chemoreceptors is minimal. It is not known whether the preoptic area is also the source of this additional drive. Rats do not pant but do possess this additional respiratory drive at raised body temperatures. We have therefore tested whether the preoptic area of the hypothalamus is the source of this additional respiratory drive in rats. Urethane anaesthesia and hyperoxia were used in eleven rats to minimise behavioural and chemical drives to breathe. The presence of the additional respiratory drive was indicated if rhythmic diaphragmatic EMG activity reappeared during hypocapnia (a mean Pa,CO2 level of 21+/-2 mm Hg, n = 11), induced by mechanical ventilation. The additional respiratory drive was absent at normal body temperature (37?C). When the temperature of the whole body was raised using an external source of radiant heat, the additional respiratory drive appeared at 40.6+/-0.5 degrees C (n = 3). In two further rats this drive was induced at normal body temperature by localised warming in the preoptic area of the intact hypothalamus. The additional respiratory drive appeared at similar temperatures to those in control rats in three rats following isolation of the hypothalamus from more rostral areas of the brain. In contrast, the additional respiratory drive failed to appear at these temperatures in three rats after isolating the hypothalamus from the caudal brainstem, by sectioning pathways medial to the medial forebrain bundle. Since the preoptic area is known to contain thermoreceptors and to receive afferents from peripheral thermoreceptors, the results show that this area is also the source of the additional respiratory drive at raised body temperature in anaesthetised rats.     

Direct septo-hypothalamic projections in the rat.

Axonal projections from neurons located in the medial and lateral septal nuclei (MSN and LSN) were traced autoradiographically. The MSN projected bilaterally via a midline route to the diagonal band of Broca (DBB), the preoptic area (POA), the suprachiasmatic (SCN), paraventricular (PVN), ventromedial (VHM) and arcuate (ARC) nuclei including the median eminence (fiberous zone). Lateral coursing fibers traveled with the medial forebrain bundle (MFB) to the supraoptic (SON) and pre- and supra-mammillary nuclei. The majority of LSN axons projected to, and terminated in, the MSN. Fibers projected ipsilaterally through the POA, SON, SCN, ARC, ME and MMN with axonal projections observed throughout the MFB. In summary, the neurons of the MSN project to the medial hypothalamic nuclei via a midline route while LSN axons projected strongly to the MSN with the remaining fibers coursing along the ipsilateral MFB to terminate in several hypothalamic nuclei. These data indicate that a direct septo-hypothalamic pathway exists in the rat.     

LHRH pathways in rat brain: 'deafferentation' spares a sub-chiasmatic LHRH projection to the median eminence

Localization of luteotrophic hormone-releasing hormone (LHRH) was examined by immunocytochemistry in untreated male rats and rats that received an anterior hypothalamic deafferentation. Gonadotrophic function was assessed by examining testicular weight and morphology. All of the antisera used in this study were able to reveal LHRH cell bodies and fibers. Cells from the medial preoptic area, (particularly the preoptic periventricular or median preoptic nuclei) and lateral anterior hypothalamus sent axons to the median eminence. The fiber tracts were loosely organized into (1) a tract that coursed through the organum vasculum of the lamina terminalis between the optic nerves and along the ventral surface of the optic chiasm; (2) a tract that coursed to the organum vasculum from the preoptic area and then traversed along the floor of the third ventricle; (3) a tract that coursed from the medial preoptic area to the median eminence along the lateral walls of the third ventricle; and (4) a tract that arose from the more caudal portions of the LHRH cell field in the lateral preoptic and lateral anterior hypothalamus, coursed along with the fibers of the medial forebrain bundle and turned medially at the caudal hypothalamus to enter the median eminence. An anterior cut which served most of the connections between the medial preoptic area and hypothalamus but did not penetrate through the optic chiasm served tract 3 and most of tracts 2 and 4, but spared the subchiasmatic projection (tract 1). The fibers that remained in the median eminence were sufficient to retain gonadotrophic function. This study provides an explanation for the variable effects of deafferentation and lesions of the anterior hypothalamus and preoptic area on gonadotrophic function.     

Tonic activity of alpha1 adrenergic receptors of the medial preoptic area contributes towards increased sleep in rats

Several studies have suggested that noradrenergic afferents to the medial preoptic area might be involved in hypnogenesis and in lowering the body temperature, and that the alpha1 adrenergic receptors might be mediating these responses. This study was undertaken to find out the changes in sleep-wakefulness and body temperature in rats, when these adrenergic receptors of the medial preoptic area are blocked by alpha1 selective antagonist, prazosin. Adult male Wistar rats were chronically implanted with electrooculogram, electroencephalogram and electromyogram electrodes for sleep-wakefulness assessment, and a bilateral guide cannula for microinjection of prazosin at the medial preoptic area. A radio-transmitter was implanted in the abdomen for telemetric measurement of body temperature in four groups of rats. Sleep-wakefulness was also assessed telemetrically in four other groups of rats. Sleep-wakefulness recordings from these rats were done in a specialized chamber, where they could move about freely and select the ambient temperature which they prefer. Prazosin induced a dose dependent increase in wake period and in body temperature, when microinjected into the medial preoptic area. Results suggest that preoptic alpha1 adrenergic receptors mediate hypnogenic and hypothermic responses. It is proposed that the noradrenergic afferents to the medial preoptic area, by tonic activation of alpha1 adrenergic receptors, contribute towards increase in sleep especially during the daytime.     

Thermosensitivity of preoptic neurones in a hibernator at high and low ambient temperatures

Summary The effect of ambient temperature on the thermosensitivity of preoptic neurones was studied in euthermic golden hamsters. At skin temperatures (T_sk) of 20°C, preoptic units were still responsive to hypothalamic temperatures (T_hy) below 10°C, while at T_sk=36°C these neurones became inactive at T_hy=15°C on the average. These studies suggest that thermoreceptive preoptic neurones, influenced by a high activity of cutaneous cold-receptors, are capable of sensing core temperatures even in deep hibernation.Supported by the Deutsche Forschungsgemeinschaft, Wu 63/2     

Orexin A (hypocretin-1) application at the medial preoptic area potentiates male sexual behavior in rats

The medial preoptic area plays an important role in the regulation of male sexual behavior in rats, and this area receives orexinergic inputs. The role of orexinergic inputs in the medial preoptic area in sexual behavior has not been studied, though they have been shown to play a role in some other physiological functions. In this study, the changes in male sexual behavior in rats were studied after local injection of orexin A (Hypocretin-1) at the medial preoptic area. The results of the study showed that orexin A application at the medial preoptic area increased sexual arousal as well as the copulatory performance. Sexual arousal is one of the physiological stimuli, which influences wakefulness. It is possible that the earlier reports showing increased wakefulness, on application of orexin A at the medial preoptic area/basal forebrain, has a contribution from sexual arousal.     

Ventral midbrain involvement in copulatory behavior of the male rat

Stimulation bound copulation was obtained from a ventral midbrain extension of the hypothalamic medial forebrain bundle. Electrical stimulation at this site accelerated the achievement of ejaculation and the resumption of copulation after ejaculation. Sexual activity was temporarily depressed immediately after stimulation. The results are discussed in terms of a preoptic medial forebrain bundle ventral midbrain system influencing copulation in the male rat.     

Effects of NMDA lesions of the medial basal forebrain on LH and VTA self-stimulation

Rewarding stimulation of the medial forebrain bundle (MFB) increases Fos-like immunoreactivity in many brain areas, including an ipsilateral, basal forebrain region extending from the medial preoptic area (MPO) to the lateral preoptic area, and substantia innominata. Excitotoxic lesions of the lateral portion of this region have been found to produce large sustained or transient increases in the number of pulses required to maintain half-maximal lever-pressing (required number of pulses) for MFB stimulation. In the present study, changes in self-stimulation of the lateral hypothalamus and ventral tegmental area were assessed following excitotoxic lesions of more medial structures, including the MPO and bed nucleus of the stria terminalis. Increases in the required number of pulses (up to 0.16 log10 units) were seen in only 2 of 10 subjects. In two other rats, the reward effectiveness of the stimulation was moderately increased after the lesion as manifested in decreases of up to 0.14 log10 units in the required number. No appreciable change from baseline was seen in the remaining six subjects. The simplest interpretation of these results is that neurons with cell bodies in the medial portion of the basal forebrain may make a smaller contribution to the rewarding effect of MFB stimulation than neurons in the lateral portion.     

Microstimulation mapping of the basal forebrain in the anesthetized rat: the "preoptic locomotor region".

Previous studies have indicated that the basal forebrain at the level of the preoptic area contains neurons which participate in the initiation of locomotion. This study attempted to localize those neurons by mapping sites at which 25- and 50-microA stimulation (50 Hz, 0.5 ms cathodal pulses, 10-s trains) initiated hindlimb stepping. Anesthetized rats were held in a stereotaxic apparatus supported by a sling so that stepping movements rotated a wheel. Anesthesia was maintained by periodic injections of Nembutal (7 mg/kg) supplemented by lidocaine injections. Stimulation was applied through 50-70-microns diameter pipettes filled with 2 M NaCl at approximately 1600 sites in the basal forebrain, adjacent thalamus, and striatum. A circumscribed grouping of 25-microA locomotor sites, centered in the lateral preoptic area, defined the preoptic locomotor region. It extended into the ventral bed nucleus of the stria terminalis, the lateral part of the medial preoptic area, the anterior hypothalamic area, the medial and rostral parts of the ventral pallidum, medial substantia innominata, and the horizontal limb of the diagonal band. This general region is known to project to the midbrain locomotor region and the ventral tegmental area; it is proposed to initiate locomotion in service of primary motivational systems. Among the structures generally negative for locomotor sites were the dorsal and ventral striata, septal complex, bed nucleus of stria terminalis, and lateral ventral pallidum and substantia innominata. These findings indicate that low current stimulation applied to a circumscribed area centered in the lateral preoptic area produces locomotor stepping in the anesthetized rat. Whether the activated elements in this preoptic locomotor region are cells or fibers is not yet known. The degree of localization afforded by these findings indicates that the areas that are most likely to contain the mediating elements are quite limited in extent.     

Role of noradrenergic fibers of the preoptic area in regulating sleep

The preoptic area (POA) has noradrenergic (NE) terminals, and this area controls sleep apart from body temperature and reproduction. The destruction of catecholaminergic (CA) terminals in the POA produced a decrease in sleep in rats. This effect was shown to be due to the destruction of NE and not dopaminergic terminals. The rats, which were hyperthermic after the destruction of CA fibers in the POA, preferred a lower ambient temperature. Though they were unable to have normal amount of sleep after lesion, it did not affect their behavioral thermoregulation. Acute total sleep deprivation for 48 h led to a significant decrease in noradrenaline, increase in the level of metabolites of monoamines, and an enhancement in the number of dendritic spines at the medial preoptic area (mPOA). Enhanced sleep pressure during sleep deprivation could have led to a higher release of noradrenaline, and an increase in dendritic spines in the mPOA. Arousal was produced by application of noradrenaline at the mPOA, whereas the alpha antagonists produced sleep in free-moving rats. This was in contrast to the increased wakefulness produced by the destruction of NE terminals. As wakefulness and sleep, respectively, were induced on local application of alpha-2 antagonist and agonists, it was suspected that the noradrenaline and alpha antagonists might have acted on the alpha-2 receptors, which are predominantly present on the pre-synaptic terminals. Sleep produced by noradrenaline, which was locally applied at the mPOA, after destroying the NE terminals, further confirmed this possibility. Hypothermia and sexual arousal produced by application of alpha- and beta-adrenergic agonists at the mPOA would have contributed towards the wakefulness induced by these drugs in normal rats. Thus, the available evidence shows that the NE fibers in the POA are involved in the induction of sleep.     

The effect of noradrenaline, injected into the hypothalamus, on thermoregulation in the cat.

1. Noradrenaline (NA) was microinjected into the anterior hypothalamic/preoptic area(AH/POA) of unanaesthetized cats held at ambient temperatures of 10, 22 or 35 degrees C. Loci in which injection of NA caused body temperature changes were also found to be sensitive to the febrile action of PGE1. 2. At all ambient temperatures, NA caused a dose-dependent fall in body temperature. However the mechanisms by which these temperature changes were brought about varied at different ambient temperatures. In cats maintained at the higher ambient temperature, NA activated heat loss mechanisms whereas in the cats maintained in the 10degrees C environment, the major effect of NA injection was an inhibition of heat conservation and heat production mechanisms. 3. We conclude that NA acts in cats not only as an inhibitor of heat conservation and production, but also acts in an excitatory manner on an active heat loss pathway within the AH/POA.     

Electrical self-stimulation deficits in the anterior and posterior parts of the medial forebrain bundle after ibotenic acid lesion of the middle lateral hypothalamus

The aim of the present study was to analyse the involvement of the intrinsic neurons located in the middle lateral hypothalamus in electrical self-stimulation measured with electrodes in the anterior and posterior parts of the medial forebrain bundle. In rats without hypothalamic lesions, self-stimulation rates from both anterior and posterior electrodes were similar on either side of the brain. For all rats with ibotenic acid-induced lesions in the lateral hypothalamus, self-stimulation rates were lower with electrodes in the area of the lesion, while self-stimulation on the contralateral side was normal. In rats with electrodes in the anterior hypothalamus, the lesion produced a large deficit when stimulation was applied to the anterior electrode ipsilateral to the lesion. Only three rats showed a decrease in self-stimulation with stimulation of the posterior hypothalamic electrode ipsilateral to the lesion; self-stimulation of the other three rats was normal. These results suggest that self-stimulation in the anterior part of the medial forebrain bundle is supported by long fibers originating in the middle part of the lateral hypothalamus, while self-stimulation in the posterior part of the lateral hypothalamus can be influenced by another system not involved in reward processes observed in the rostral part of the medial forebrain bundle.