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Single stimuli applied to the posterior hypothalamus evoke in the visual cortex of anesthetized rabbits a hypothalamic--cortical response with short latency, marked premarily--positive and negative components, and secondary positive wave of a large amplitude. It seems that projections from the posterior hypothalamus to the cortex are multiple, pass through different subcortical structures and terminate with different synaptic organizations. Single stimuli applied to the posterior hypothalamic nuclei with intervals from 700 to 100 msec facilitate a visual evoked potential due to enhancement of the negative component. Apart from the facilitation of the visual response, the area where the potential can be recorded is enlarged by single stimuli applied to the posterior hypothalamic nuclei.

The norepinephrine content of the whole brainstem and of its different parts and the epinephrine and norepinephrine (NE) content in the blood and adrenals in dogs and rats during ontogenesis were studied. The catecholamine (CA) level in the blood and different parts of the dog brainstem increased to the age of 20-30 days and then decreased. The NE value of the whole dog brainstem increased to the age of 9-30 days, and then decreased. The content of NE of the rat brainstem increased to the age of 120 days and then decreased. The amount of CA of the dog and rat adrenals increased progressively from birth to adulthood. The CA brain and adrenal level of dogs during postnatal ontogenesis was lower than in rats.

Changes of unit activity in different nuclei of the posterior hypothalamus induced by intravenous oxytocin injections were studied in acute experiments on Wistar rats anaesthetized with nembutal. Influence of nonapeptide was dose-dependent. Latencies of various neuronal reactions were different. Mechanisms of oxytocin regulation of neuronal activity in the posterior hypothalamus are discussed.

Thirty units that responded antidromically to electrical stimulation of the zona incerta (ZI) or the dorsal portion of hypothalamus were recorded in the nucleus tractus solitarii (NTS). These units were analyzed in relation to hepatoportal afferent inputs. Electrical stimulation of the hepatic branch of the vagus nerve facilitated six units (facilitatory units) and suppressed 10 units (suppressed units). Effect of the portal infusion of hypertonic saline was examined on six facilitatory and eight suppressed units. One facilitatory unit and one suppressed unit increased their discharge rates in response to portal infusion. Four facilitatory units and one suppressed unit decreased their discharge rates in response to the same stimulation. Increased or decreased discharge rates in response to portal infusion of hypertonic saline were observed in units that responded antidromically to electrical stimulation of the paraventricular hypothalamic nucleus, the lateral hypothalamic area, or the ZI. It is concluded that hepatoportal osmoreceptive signals are conveyed to the hypothalamus or the ZI directly from the NTS.

The antigenic stimulation induces alteration of the ultrastructure of neurons, synapses and glial cells in area hypothalamic posterior of the brain of experimental animals. Swelling of mitochondria, partial or total destruction of cristae points out to the involvement of the energy apparatus of neurons and synapses. An intensive formation of antibodies is accompanied by an increase in the structural functional activity of neurons. Ultrastructural alterations of some organelles of neurones, synapses and glial cells are connected with adaptive reactions of intracellular structures and have a non-specific nature.

The electrical activity of the dorsal and ventral hippocampus and of the anterior and posterior neocortex is described and illustrated during the development of trained operant behavior in water-deprived cats learning to bar-press for water reward under three operant conditioning schedules: (a) continuous reinforcement; (b) alternating 10 sec periods of reinforcement and non-reinforcement; and (c) mixed reinforcement and non-reinforcement with special auditory and visual cues. In addition, the contrasting effects of 100 c/sec electrical stimulation of the medial and lateral hypothalamic systems upon hippocampal electrical activity and operantly trained behavior are reported. During the early stages of learning to bar-press for water reward, when close attention to the bar and water-well are required, hippocampal electrical activity manifests synchrony (theta rhythm) and neocortical electrical activity is desynchronized. Subsequently, as bar-pressing performance improves and requires little attention to the manipulanda, the pattern of hippocampal and neocortical electrical activity is one of irregular slow waves mixed with low voltage high frequency activity, characteristic of relative inattention and automatic performance. During alternating or mixed reinforcement and non-reinforcement schedules of operant training differential effects are observed during reinforcement and non-reinforcement periods, the latter being characterized generally by lower voltage, mixed low and high frequency activity, except when orienting and shifting of attention occurred with associated theta rhythm bursts. Stimulation of the medial hypothalamic system has a striking inhibitory effect upon bar-pressing for water reward. Bar-pressing ceases for many minutes but its eventually resumed at the pre-stimulation rate. In contrast, stimulation of the lateral hypothalamic system only interrupts bar-pressing for a matter of seconds. Possible causes of these differential effects, and especially the prolonged inhibition of bar-pressing induced by medial hypothalamic stimulation, are discussed.

After 3, 15 and 30 sessions of electrical stimulation of the hypothalamus by means of stereotaxically implanted bipolar electrodes into the area hypothalamica posterior, in the cortex of the cerebellar hemispheres, predominantly in the ganglionic layer, certain reactive, as well as poorly and intensively manifested pathological changes develop in neural and glial cells. Mosaicism of Purkinje's cells lesions within the layer, the state of their cytoplasmic matrix, granular endoplasmic reticulum and mitochondria, essential shifts in activity of oxidation-reduction enzymes at a simultaneous disorder in blood circulation and decreased content of catecholamines in the neural structures of the cerebellar vessels make it possible to estimate the process as centrogenic and neurodistrophic.

Polygraphic 23-hr recordings were carried out in 25 adult cats in order to examine the effects of both systemic and local injections of various histaminergic and antihistaminergic drugs on sleep-waking cycles. alpha-Fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, when injected intraperitoneally at a dose of 20 mg/kg, induced a significant increase in deep slow wave sleep (S2) and a decrease in wakefulness (W), without modifying light slow wave sleep (S1) and paradoxical sleep (PS). Intraperitoneal injections of mepyramine (1 mg and 5 mg/kg), a well-known histamine H1-receptor antagonist, increased deep slow wave sleep and decreased wakefulness, as well as paradoxical sleep. Bilateral injections of alpha-FMH (50 micrograms/1 microliter) into the ventrolateral posterior hypothalamus, where histamine immunoreactive neurones have been recently identified, resulted in a significant decrease in wakefulness and increase in deep slow wave sleep. Similarly, injections of mepyramine (120 micrograms/1 microliter) in the same structures caused a significant decrease in wakefulness and an increase in deep slow wave and paradoxical sleep as well. In contrast, local injections of SKF-91488 (50 micrograms/1 microliter), a specific inhibitor of histamine-N-methyltransferase, led to a significant increase in wakefulness and decrease in both slow wave sleep (SWS) and paradoxical sleep. Injections of histamine, at doses of 5, 30 and 60 micrograms/1 microliter, also increased wakefulness and decreased slow wave sleep dose dependently, while these effects were completely blocked by pretreatment with mepyramine. The results suggest that histaminergic systems in the hypothalamus play an important role in arousal mechanisms and their actions are mediated through H1-receptors.

Responses of single units of posterior, anterior, ventromedial and lateral hypothalamus to stimulation of abdominal trunk of the vagus nerve were recorded in anesthetized cats simultaneously with the action potentials of the cervical region of the vagus nerve. 28.1% of the neurons responded to the stimulation, the pattern of responses being mainly excitatory. Vagal stimulation proved to be more effective for units of the lateral hypothalamus, 47.1% of the excitatory reactions followed stimulation of A gamma delta--B afferents and 40.4%--stimulation of C afferents of the vagus. Topical organization of the projection of these groups of visceral afferents to different regions of the hypothalamus was partially revealed. Responses of some A gamma sigma--B and C neurons to stimulation of vagus and sciatic nerves suggest convergence of visceral and somatic afferents to the "convergence" types of neurons. Some A gamma delta--B and C units, chiefly in the ventromedial hypothalamus, responded only to stimulation of visceral vagal afferents. The sensory properties of "visceral" neurons of the hypothalamus are discussed.

The possible occurrence of central sympathetic dysfunction during development of spontaneous hypertension was studied by recording aortic pressure and sympathetic nerve activity concurrently during electrical stimulation of the posterior hypothalamus in 9-wk-old Kyoto-Wistar rats. Even at this early age, basal levels for both measurements were already elevated significantly in those with spontaneous hypertension. Increases in sympathetic neural firing induced by graded hypothalamic stimulation were always followed by corresponding increases in blood pressure; magnitude of both effects was appreciably larger in spontaneously hypertensive than in normotensive rats, as was the vasodepression caused by blocking autonomic ganglia with pentolinium. By contrast, pressor responses to injected norepinephrine were almost equal thereby suggesting that cardiovascular reactivity was unaltered and that enhanced responsiveness to hypothalamic stimulation was directly due to the concomitant increase in sympathetic nerve activity. Although the exact site from which sympathetic hyperactivity originates was unidentified, our results support the interpretation that sympathetic mechanisms involving the posterior hypothalamus participate in elevating blood pressure during development of spontaneous hypertension in rats.

Averaged evoked potentials (EP) to a CS (flash) were recorded sequentially in classical appetitive conditioning, satiated state after appetitive conditioning, highly alert state by noncontingent shocks, and classical aversive conditioning from a rat. The EPs were obtained from the central gray matter, superior colliculus, perifornical hypothalamic area, dorsal frontal cortex, and occipital cortex. Alterations unique to aversive conditioning were found in the dorsal frontal cortex (40–60 msec in latency) and in the perifornical hypothalamus (80–120 msec) but not in the central gray or occipital cortex. The frontal cortex might start processing information related to aversive or defensive emotion before the perifornical hypothalamic area might do it.

The following investigations concerning scoliosis are in progress at Tokushima University: (1) a study of the incidence of equilibrial dysfunction; (2) a study of the nature of dysequilibrium, with special reference to the origin (functional or organic); (3) a field survey of scoliosis associated with equilibrial dysfunction in school children; (4) a study of experimental and clinical metabolic disturbances in scoliosis; (5) a study of postural reflex in experimental animals; (6) a study of scoliosis in animals with experimentally produced brain stem lesions; and (7) a study of scoliosis in animals with experimentally produced lesions in the posterior part of the hypothalamus. The hypothetic assumption is that dysfunction of the postural reflex regulation induced by functional or organic disorders at the brain stem center may play an important part in the development of idiopathic scoliosis during the period of rapid growth in children.

The functional state of the rabbit brain activating system was evaluated by the activation reaction, and the thalamic inhibitory system, by the recruiting response. At the initial phase of hypoxia, excitability of the activating system was enhanced, while at the same time the eugmenting phase of the recruiting response diminished and its inhibitory phase was prolonged. At the "altitude" of about 7000 m, against the background of a gradual weakening of the ascending activating influence of the reticular formation and the hypthalamus, the recruiting response assumed the form of regular; equally negative potentials, which testifies to the activie synchronizing influence of the inhibitory system. At a "rise" to 8500 m, against the background of slow synchronized EEG waves, in most cases there was no activation reaction to the stimulation of the reticular formation and hypothalamus. Neither was there any recruiting response to the stimulation of non-specific thalamic nuclei.

The number of plaque-forming cells (PFC) in the spleen of rats immunized with sheep red blood cells after the injury of the anterior or the posterior portions of the medial hypothalamus, and also of the thalamus displayed no significant difference from the number of PFC in the spleen of intact animals. The titres of hemolysing and hemagglutinating antibodies in the animals with injuries of the mid-brain were somewhat lower than in the intact animals. A reduction of the circularing antibodies level was not associated with localization of the foci of injury and apparently served as the sequence of the craniocerebral trauma.

The connections between the areas 'S' which have been previously described as the ventromedullary sites of the action of clonidine and the posterior hypothalamus have been investigated. Superficial electrocoagulation of the left area 'S' suppresses the pressor response to electrical stimulation of the homolateral part of the posterior hypothalamus. Although such medullary lesions cause a significant reduction of the mean arterial pressure, the contralateral hypothalamic stimulation can still increase blood pressure. Clonidine it self applied topically (8 micrograms/kg) to the ventral face of the brain stem decreases the blood pressure response to liminal hypothalamic stimulation. It is concluded that efferent pathways, which are involved in vasomotor regulation, originate in the posterior hypothalamus and run through the ventrolateral part of the brain stem. The mechanism of the blocking effect of clonidine on these pathways is discussed.

Stimulation electrodes were implanted in 63 rats at a total of 208 sites in the diencephalon and midbrain. The sites were tested for elicited forward locomotion, i.e., alternate stepping of the forelimbs and/or hindlimbs, while the rats stood on a treadmill belt in a 27 X 9 X 24-cm chamber. Current levels of 50-300 microA and pulse frequencies of 50, 100 and 154 Hz were presented as single 5-sec trains and as 20 repetitive trains of 1-sec duration with a 3-sec intertrain interval. Locomotion was elicited with low current (50 or 100 microA) single trains at 28% of the sites. Of the regions sufficiently well sampled to warrent comparisons, two showed high densities of locomotion-positive sites with single low current trains. They were the medial hypothalamus (the dorsomedial and the posterior nuclei) and the ventral tegmental area. The medial forebrain bundle and the zona incerta were generally positive but many sites in these regions required repetitive trains. Among the regions with few locomotion-positive sites were the subthalamic nucleus, the fields of Forel and the habenular complex. In the dorsal midbrain, in and around the central gray, low current single trains elicited leaping. The results are discussed in terms of the existence of a delimited subthalamic locomotor region and a ventral midbrain locomotor system independent of a dorsal midbrain system.

Dynamics of neuronal activity of the posterior hypothalamus in the sleep-wakefulness cycle was studied in free moving cats using mobile metal microelectrodes. Computer analysis and statistical treatment of the data have shown that the majority of neurons (89.3%) in the above-mentioned area discharge with high frequency during active wakefulness and emotional stage of paradoxical sleep; the frequency of discharges decreases during passive wakefulness and nonemotional stage of paradoxical sleep and is the lowest in the slow wave sleep though it has been higher than at the other states. Comparatively small number of neurons (3.6%) show opposite dynamics of the activity. They fire more intensely during slow wave sleep and the frequency of discharges decreases during active wakefulness and paradoxical sleep. In posterior hypothalamus some neurons (7.1%) are found which fire intensely during active wakefulness as compared with slow wave sleep and paradoxical sleep. The neurophysiological mechanisms for regulation of the sleep-wakefulness cycle and the involvement of posterior hypothalamus in this process are discussed.

Effects of desoxynupharidine hydrochloride (DN) on the central nervous system of cats were studied using electric physiological techniques. With regard to the EEG arousal responses, DN (1-3 mg/kg, i.v.) inhibited the responses induced by midbrain reticular formation and posterior hypothalamus (P-Hypo) stimulation. The threshold voltage of stimulation was elevated. DN decreases the amplitude of the augmenting response and the recruiting response induced by the stimulation of specific and non-specific pathways in the thalamus. As to the evoked potentials in the somatosensory area I, DN decreased the amplitude of the fast and late components. This compound slightly inhibited the monosynaptic and polysynaptic reflexes, in the spinal cats. With regard to autonomic responses on stimulation of the P-Hypo, DN decreased contractions in the nictitating membrane, the hypertensive action and the galvanic skin response. Our findings indicate that the inhibitory effects of DN on the central nervous system may be related to the brainstem reticular formation and the hypothalamus activating system, the non-specific pathway, the specific pathway and the limbic system etc., and may involve the central anti-adrenergic actions.

To determine whether the locomotor stimulant and the anorexic actions of thyrotropin-releasing hormone (TRH) and amphetamine were mediated through the hypothalamic nuclei, rats were infused with either TRH or amphetamine through previously implanted hypothalamic cannulae. Administration of TRH or amphetamine into the ventromedial hypothalamus, but not the lateral hypothalamus and the anterior hypothalamus, caused locomotor stimulation in rats. On the other hand, administration of TRH or amphetamine into the lateral hypothalamus, but not the ventromedial hypothalamus or the anterior hypothalamus, caused a reduction in food consumption without affecting relative water intake (or water-to-food ratio) in the rat. The data indicate that the ventromedial hypothalamus is the most sensitive site of the TRH- or amphetamine-induced locomotor stimulation and the action of TRH or amphetamine on the lateral hypothalamus is also a possible mechanism mediating anorexia.

Using the evoked potentials (EP) studies have been made on functional connections of different fields (CA1, CA3) of the dorsal hippocamp with phylogenetically different parts of the hypothalamus in rabbits. It was shown that during stimulation of both the field CA1 and the field CA3 of the hippocamp, the EP are widely present in nuclear structures of the posterior hypothalamus (supramammilary area, the posterior hypothalamic area, mammilary bodies). In the anterior hypothalamus (area preoptic medialis), the EP were recorded only during stimulation of the field CA1 in the dorsal hippocamp.

Food-satiated goldfish were stimulated in tanks containing food on the surface of the water and on the bottom of the tank. Various components of the feeding response were seen, and complete feeding was observed, which was elicited from sites in the postero-medial hypothalamus. Evidence is put forward to support the supposition that the full response was due to a change in feeding motivation, rather than to changes in sensory or motor factors. Other types of behaviour, such as fin movements and swimming, could not be identified as part of any normal ethological sequence. However, vertical movements and gas-spitting responses indicated a possible hypothalamic control of buoyancy. None of the behaviours observed was seen to change in a social context.

The influence of low- and high-frequency stimulation of anterior, tuberal and posterior hypothalamic areas on the spontaneous rhythmogenesis in the ureter smooth muscles and on arterial blood pressure, was studied in anesthetized cats. High-frequency stimulation of all hypothalamic areas induced pressor responses with activating effects on motor activity of the ureter. The changes in the ureter rhythmic activity were synchronous with those of systemic arterial blood pressure. The low-frequency stimulation induced both pressor and depressor responses in different proportion. The depressor responses were not accompanied by any changes of the ureter rhythmic activity. Possible mechanisms of reversal of vasomotor responses in stimulation of hypothalamus, organization of sympathico-activating and sympathoinhibitory mechanisms and hypothalamic regulation of rhythmogenic function of the ureter, are discussed.

Rats exhibiting self-stimulation behavior through chronic electrodes implanted in the posterolateral part of the hypothalamus were subcutaneously injected with low doses (0.003–0.3 mg/kg) of naloxone. The animals were allowed to self-regulate the duration of rewarding brain stimulation. It was found that naloxone increases the duration of self-stimulation in rats in which the brain stimulation had previously been associated with footshock. Vehicle injections or injections of naloxone in rats that had not received footshock prior to testing, did not modify self-stimulation behavior. It is suggested that naloxone may facilitate an aversive central component of the brain stimulation; the conditioned rats therefore increased the duration of brain stimulation to compensate for this negative process.

The cytoarchitectonic organization of the posterior hypothalamus of the cynomolgus monkey (Macaca fascicularis) was analyzed in Nissl, Golgi, acetylcholinesterase, and reduced silver preparations. The region consists of a number of cell masses that differ considerably in their discreteness and in the homogeneity of their neuronal populations. The nuclei identified include: the medial mamillary nucleus (in which at least three distinct subdivisions can be recognized—a pars medialis, a pars lateralis, and a pars basalis); the small-celled nucleus intercalatus; the large-celled lateral mamillary nucleus; a single premamillary nucleus; the tuberomamillary nucleus; the posterior hypothalamic nucleus; the caudal extension of the lateral hypothalamic area; the supramamillary area; and the paramamillary nucleus (which appears to correspond to the nucleus of the nucleus of the ansa lenticularis of other workers). As a basis for the subsequent experimental study of the efferent connections of the posterior hypothalamus, the location of each of these cell masses is described and illustrated in a series of low-power photomicrographs, as are the form and distribution of the resident neuronal populations of the various components of themamillary complex as seen in Golgi preparations.

In chronic experiments on male relatively unrestrained rats, simultaneous studies have been made on the behaviour during wake-sleep cycle and on changes in the temperature of the neocortex, posterior hypothalamus and neck muscles. Interaction of two mechanisms at the hypothalamic level is discussed, namely the development of various stages of the wake-sleep cycle and thermoregulation. Special attention is paid to the phase of rapid sleep, when the transition of an animal from homoiothermic to heterothermic conditions presumably takes place.

The tumour aetiology of precocious puberty is sometimes clinically evident when accompanied by visual disturbances or by raised intracranial pressure. It may be suspected in the presence of accelerated puberty but should also be feared in cases of apparently idiopathic precocious puberty. In the 13 cases studied, the tumour was studied in the posterior hypothalamus. Ten children underwent surgery (with additional radiotherapy in two cases). Two children died, the follow-up varying at present between 2 and 12 years. Amongst the various tumours, the hamartoma has a special nature by virtue of slow or absence of increase in tumour size. When the clinical and radiological signs suggest this type of tumour, abstention from surgery with close observation of the size of the tumour and medical slowing of puberty is advised.

Electrical responses to stimulation of different areas of the cingulate gyrus were studied in L2-L3 white rami in anesthetized and immobilized cats. The stimulation evoked a sympathetic discharge mostly consisting of a wave with a mean latency of 71.2 +/- 2.3 ms. In a few cases, the main wave was preceded by a short-latency component. Thresholds for eliciting sympathetic discharges were lower in case of stimulation of the ventral region of area 25 in comparison to those of the dorsal region of the same area. A comparative study showed that the lowest were the thresholds of hypothalamic evoked discharges, somewhat higher were the thresholds of amygdala stimulation and the highest were those of the cingulate cortex evoked discharges. In experiments with simultaneous recording of arterial pressure and cingulo-sympathetic discharges, after 10-sec period of tetanic (100/sec) stimulation of the limbic cortex, the early components were facilitated while the late component of the cingulo-sympathetic discharges was depressed. The duration of this inhibition corresponded to the period of pressure reaction and, therefore, was of a baroreceptor origin. Possible mechanisms of cingulate cortex regulation of the activity of sympathetic preganglionic neurons, are discussed.

It has been found in experiments on unanesthetized rabbits that arecoline administered to the lateral ventricle of the brain produced an action which was opposite to that of leukocytic pyrogen. It inhibited the activity of individual neurons of the posterior hypothalamus and decreased the body temperature, with this decrease being attended by the signs of intensified heat emission. Arecoline injection coupled with the central action of PGE2 was followed by an increase in the neuronal activity in the posterior hypothalamus and reduction of hyperthermal response.

Neuron discharges of the hypothalamic ventro-medial and posterior nuclei were registered in immobilized cats during electrical stimulation of the ipsi- and contralateral nerves of the brachial plexus, the 1st and the 2nd somatosensory regions (SI and SII) and the visual regions of the cortex and the reticular formation (RF) of the mesencephalon. A reversible cold block of the SI and SII failed to change the effect of the nerve stimulation. Stimulation of the postero-ventral thalamic nucleus did not change the initial activity of the hypothalamic neurons and gave rise to no neuron activity that appeared on stimulation of the SII. A conclusion was drawn that cortico-hypothalamic influences that appeared on stimulation of the nerves and the postero-ventral nucleus of the thalamus were pronounced weakly.

The decorticate cat develops sequences of locomotor movements, especially in the two posterior limbs: those appear either spontaneously, or following a single shock applied to L7 dorsal root. Using this preparation, we tested the effects of two neuroleptic agents, Thioproperazine (TZ) and Sulpiride (S), through either systemic administration or local injection into the lateral-posterior hypothalamus and into the lumbar spinal cord. TZ administered i.v. (0.5 mg/kg) suppressed all locomotor rhythms, while S induced unclear effects. The tested drugs clearly acted at the hypothalamic level, but the effects of the drugs were opposite; TZ (70 microgram) suppressed rhythms, while S (350 microgram) increased or even induced them. T2 (50 microgram) injected at the L7 cord-level abolished rhythms, and S (350 microgram) reduced their amplitude but increased the duration of locomotor sequences. The flexion reflex was never affected by these drugs. The two drugs seem to act at the spinal and the hypothalamic levels. The possible mechanisms involved in their action are discussed.

The influence of the midlateral posterior hypothalamic area (MLPHA) on arterial blood pressure and respiration was examined in the rats. Electrical stimulation produced a rapid transient increase in blood pressure and rapid shallow respiration. Glutamate, which stimulates neurons and not fibers of passage, however, caused a fall in blood pressure and slowing of respiration. Projections of MLPHA traced by horseradish peroxidase (HRP) and 3H leucine showed reciprocal connections with limbic forebrain centers but only indirect connections with brainstem cardiorespiratory centers. It is concluded that MLPHA may be a relay through which the limbic system can gain access to and depress cardiorespiratory function.

Radio-frequency lesions of tubero-infundibular region of the hypothalamus are followed by a significant increase of the mitotic rate in the small intestine glandular epithelium in rats. This increase does not occur when radio-frequency lesions are located in the anterior and posterior hypothalamus, in the dorsomedial thalamus and in the cerebral hemispheres.

Electroencephalographic (EEG) responses were recorded from preoptic, posterior hypothalamus and fronto-parietal cortical areas in mature male rats. Observations were made through stereotaxically implanted electrodes before and after an injection of clomiphene citrate (CC) in a dosage of 4 mg at varying time intervals in the same animal. The immediate response to CC injection was the occurrence of slow waves in preoptic, which later appeared in posterior hypothalamus. Slowing from posterior hypothalamus was very conspicuous, consisting of occasional high voltage rolling waves intermingled with low voltage fast components ending in discharges of long duration. Intermittent bursts of slow waves were observed as a regular feature from preoptic. By the end of two and a half hr, EEG activity of posterior hypothalamus was similar to that of preoptic. These EEG changes have been discussed with reference to hypothalamic control mechanisms for the secretion of gonadotrophins and libido display in the presence of CC.

We have studied the effects of local injections of histaminergic and antihistaminic drugs on the sleep-waking cycle in the cat. Microinjections of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, in the ventrolateral posterior hypothalamus, where histamine-immunoreactive neurons have been recently identified, resulted in a significant decrease in wakefulness (W) and increase in deep slow wave sleep (SWS). On the other hand, microinjections of SKF-91488 (Homodimaprit), a specific inhibitor of histamine-N-methyltransferase, increased W and decreased SWS and paradoxical sleep (PS). Microinjections of histamine also produced an increase of W, while this effect was abolished by pretreatment with mepyramine, an H1-histamine receptor antagonist.

Bilateral, radio-frequency destruction of the ventro-medial posterior hypothalamus (VMPH) resulted, as compared to sham-operated and control rats and evaluated in the tail-flick and vocalization tests, in a significant decrease in basal nociceptive threshold on day 4 post-surgery. By day 12, however, no significant difference between sham and lesioned rats was seen. At this time the antinociception elicited by either acute foot-shock or cold-water-immersion stress was profoundly attenuated. The antinociceptive response to various doses of morphine was not, in contrast, diminished. As established by use of radioimmunoassay, these lesions did not significantly alter hypothalamic levels of beta-endorphin, met-enkephalin, dynorphin or alpha-neo-endorphin. They did, however, produce a pronounced and significant fall in the hypothalamic content of substance P. These data are indicative that the VMPH may, via a mechanism not involving endorphins, be of importance in the determination of basal nociceptive threshold and in the generation of stress-, but not morphine-, evoked antinociception. The relationship of these findings to the interconnections of the VMPH, and to the possible significance of substance P and the pituitary in nociceptive processes, is discussed.

Autoradiography of sections from the brains of anaesthetized rats injected with [ 14 C] 2-deoxyglucose revealed neural systems unilaterally activated by rewarding electrical stimulation of the medial forebrain bundle. Since this new technique marks neural systems on the basis of their activity, it has great potential in functional neuroanatomy. The potential is easily realized in brain-stimulation studies, where systems may be driven to exceptionally high levels of activity.

In chronic experiments on dogs, preliminary stimulation of corticomedial and parvocellular basal nuclei of amygdala augmented the motor responses of the gastro-intestinal tract to subsequent stimulation of median hypothalamic structures and weakened the inhibitory effects of posterior hypothalamic structures on motility of the digestive tract. After preliminary stimulation of the hypothalamus, the motor responses of stomach and small intestine to subsequent stimulation of corticomedial and parvocellular basal nuclei of amygdala were enhanced. The data obtained suggest existence of a complex functional hypothalamo-amygdaloid interaction, the hypothalamus with its basic mechanisms of regulation of motor function of the digestive tract playing the leading part in this interaction.

Since several studies indicate that protection from lethal anaphylaxis is mediated by anterior hypothalamic (AH) lesions, we investigated the hypothesis that central nervous system perturbations can modify release of mediators from antigen-challenged sensitized lungs. Three types of perturbations were made in guinea pigs: AH perturbation (electrodes inserted and the current was applied), anterior hypothalamic sham (AS) (electrodes placed as in the AH group but no current was passed), and posterior hypothalamic (PH) perturbation (electrodes placed and the current was applied). A control group was sham operated (electrodes not inserted). Eleven days after the operation, guinea pigs receiving brain perturbations and half the control group were sensitized to the antigen ovalbumin. The other half of the control group received vehicle only (nonsensitized). Twenty-five days after this procedure, lungs were perfused in situ, and the outflows were collected before and after injection of antigen. The perfusates were assayed for immunoreactive prostaglandin and histamine, and the lungs were assayed for cAMP, guanosine monophosphate, and histamine. Release of mediators and changes in lung cyclic nucleotides after perfusion with antigen were significantly greater in all the antigen-sensitized compared to the nonsensitized animals. Within the anaphylactic groups, significant reductions in mediators and in cyclic nucleotides were found in the animals with perturbations of the AH region compared to the CO animals. The time course of mediator release was not altered. The results extend to the biochemical level, the observation that the perturbation of the AH region can markedly modify the anaphylactic response, and indicate that this effect may be due to altered release of mediators.

Adult rats (males) of the Wistar species and of SPF origin were studied for the dependence of frequency on the electric potential on EEG records of the region of the hypothalamic ventromedial nucleus and lateral hypothalamus of animals fed high-protein and high-fat diets. Similar values of control animals were used for comparison. Each group comprised seven animals. In the control animals, constantly fed the basic diet, the values of the frequency-voltage dependence remained unchanged. In the animals fed high-protein diet frequency increased with rising voltage whereas in those fed high-fat diet frequency declined with increasing voltage in both body regions under study.

The effect of electrical stimulation of anterior, medial, and posterior hypothalamus and of midbrain RF on the spleen resistance and capacitance vessels was studied in 48 anesthetized cats. The stimulatin of all the structures but the anterior hypothalamus evoked constrictory responses of the resistance vessels and decreased the blood volume in the spleen. Apart from the constriction, the stimulation of the anterior hypothalamus decreased the tonus of both kinds of vessels in some cases. The highest perfusion pressure was observed during the stimulation of anterior hypothalamus while the greatest rise of venous outflow with the briefest latency was found during the stimulation of the midbrain RF.

Rats received 1-stage bilateral or sequential unilateral (serial) lesions of the posterior hypothalamus and were tested for the ability to regulate body temperature after a lengthy recovery period. The groups with lesion differed from the sham-operated groups in the cold, although not under ambient or warm conditions. The fact that the serial lesion group performed the same as the 1-stage lesion groups in the cold is significant because earlier tests on these same animals revealed much better recovery after serial lesions in swimming, and a partial serial lesion effect in open field performance.

This paper focuses mainly on those findings derived from lesion studies on the rat which help to identify ensembles of neural structures concerned with the expression of previously learned responses. At the outset, the use of the lesion method in the search for those neurological circuits underlying memory is defended. This is followed by an evaluation of neocortical and subcortical systems in long-term memory. Subsequently, a modest list of tentative functional neural "complexes" involved in the maintenance of certain classes of learned responses is given, based largely upon the author's own research. It is concluded that the key to the understanding of the neurological substrates of long-term memory lies in the identification of those subcortical sites which interact with neocortical sites in the performance of complex learned tasks. The most likely subcortical sites involved in this interaction appear to inhabit the regions of the basal ganglia, limbic midbrain area, and ventral portions of the brainstem reticular formation.