Reactions of neurons of orbitofrontal cortex to stimulation of limbic system formations

The reactions of 164 neurons of the orbitofrontal cortex (OFC) to stimulation of the mediodorsal nucleus of the thalamus (MD), the amygdaloid complex, and various sections of the hypothalamus, were investigated in acute experiments on cats. Stimulation of the MD led to the development in OFC neurons of reactions with a short (sometimes less than 6 msec) and stable latent period. Similar reactions were observed upon stimulation of the lateral amygdaloid nuclei. Stimulation of the basal and central nuclei of the amygdala evoked synchronization of the discharges in OFC neurons. Stable responses of OFC neurons developed from nuclei of the hypothalamus only in the lateral region. Stimulation of the other nuclei of the hypothalamus was accompanied by irregular responses or synchronization of the discharges. In an analysis of the material obtained, the functional characteristics of the connections between the structures investigated and OFC neurons were examined.State Medical Institute, Kemerovo. Translated from Neirofiziologiya, Vol. 3, No. 5, pp. 484–490, September–October, 1971.     

The interrelations between neurons of the amygdala and hypothalamus during conditioning with selection of food reinforcement quality in cats

Three cats were subjected to appetitive instrumental conditioning to light by the method of the "active choice" of the reinforcement quality. The short-delayed conditioned bar-pressings were reinforced by bread-meat mixture and the delayed response by meat. The animals differed in behavior strategy: two animals preferred bar-pressing with long delay (the so-called "self-control" group) and one animal preferred bar-pressing with short delay (the so-called "impulsive" group). The multiunit activity of the basolateral amygdala and nucleus lateralis of the hypothalamus was recorded through chronically implanted nichrome wire semimicroelecrodes. The interactions between the neighboring neurons in the lateral hypothalamus and basolateral amygdala (within the local neuronal network) and between the neurons of the basolateral amygdala and lateral hypothalamus (distributed neuronal networks in the direction amygdala--hypothalamus and vice versa) were evaluated by means of statistical crosscorrelation analysis of spike trains. The crosscorrelational interneuronal connections in the delay range of 0-100 ms were examined. It was shown that the number of crosscorrelations between the discharges on neurons both in the local networks of basolateral amygdala and distributed networks was significantly higher in "impulsive" cats. In both groups of animals, the percentage of crosscorrelations between neighbouring neurons in the local networks of the lateral hypothalamus was similar. We suggest that the local networks of the basolateral amygdala and amygdalar-hypothalamic distributed neuronal networks are involved in the system of brain structures which determine the individual features of animal behavior.     

Behavioral reactions to stimulation of the emotiogenic zones of the brain in the rats with different individual experience

Emotional reactions evoked by electric stimulation of the hypothalamus and amygdala were studied in white outbred rats, grown either in conditions of isolation or in community. The method of self-stimulation in shuttle box was used. The values of self-stimulation reaction were significantly lower and those of avoidance reactions were higher in animals bred in isolation. Their food-procuring behaviour disappeared faster at stimulation of the negative emotiogenic zones. The observed differences are due to plastic reorganization of the brain reinforcing systems.     

Analysis of hemodynamic reactions induced by stimulation of the hypothalamus in alert animals

Electrical stimulation on the hypothalamus in alert cats increases the blood pressure and inhibits the baroceptor reflexes. In animals with extirpated sinocarotid and aortic nerves the pressor reactions are perversed to depressor ones at threshold stimulation of the hypothalamus. Meanwhile suprathreshold stimulation of this organ leads to emergence of depressor-pressor responses. It is suggested that inhibition of the baroceptor reflexes is one of the mechanisms of the hypertensive reaction emergence at stimulation of the hypothalamus.     

Plasma growth hormone responses to microinfusion of noradrenergic agents into or electrical stimulation of the hypothalamus and amygdala in baboons

In nine baboons (Papio papio) guide cannulae and electrodes were stereotaxically implanted into the medial basal or lateral hypothalamus, the anterior hypothalamus or the dorsal amygdala. Plasma GH responses were measured after microinfusion (1 microliter) of the alpha2 adrenergic agonist, clonidine, or the beta adrenergic antagonist, propranolol, or electrical stimulation, in each of these sites. Clonidine, 100 nmol/microliter, infused into the medial basal or lateral hypothalamus elevated plasma GH levels by 5-30 ng/ml, 30-45 min post-infusion. Plasma GH responses to clonidine infused into the anterior hypothalamus or the dorsal amygdala were all less than 10 ng/ml. The prior, intravenous, administration of piperoxane, 1.0 mg/kg prevented GH responses to clonidine. Propranolol, 50 nmol/microliter, infused into the dorsal amygdala consistently increased plasma GH levels by 5-15 ng/ml. Electrical stimulation of the medial basal or lateral hypothalamus elevated plasma GH levels by 7-35 ng/ml, 15-45 min post stimulation. Electrical stimulation of anterior hypothalamus or dorsal amygdala did not alter plasma GH levels. The stimulation of alpha 2 adrenergic receptors in the medial basal or lateral hypothalamus of the baboons appears to facilitate GH release.     

Evoked activity of the cat hypothalamus and amygdala under food motivation and in emotional stress

Amplitude-latency characteristics of auditory evoked potentials (EPs) recorded in bilateral points of the lateral hypothalamus and amygdala were studied under food motivation, in emotional stress (presentation of dogs) and tentative reactions. In the state of hunger, as compared with safety, the latencies of P1, N2 components of EP in hypothalamus, and P1, N2, N3 in amygdala were decreased and their amplitudes were changed. Changes in the left side of both structures were more pronounced. During presentation of dogs, decreases of latencies of all EP components including N1 occurred in hypothalamus and amygdala, changes in hypothalamic potentials were more pronounced on the right side, whereas in the amygdala--on the left side. During tentative responses to emotional-neutral stimuli, the latency of EP increased. It was concluded that sensory reactivity of hypothalamus and amygdala increased in motivational-emotional states. It was supposed that the side of dominance of structure may be related both to the factors of active or passive behavior during fear and the genesis of emotion (motivational or informational).     

The reactions of cats to species-specific acoustic signals during electrical stimulation of the hypothalamus before and after the removal of the sensorimotor area of the cortex

In conditions of chronic experiment cats reactions were studied to species-specific acoustic signals (SAS) presented separately and against the background of the electric stimulation of the hypothalamus before and after partial bilateral ablation of the sensorimotor area of the cortex (SMC). It was shown that separately presented SAS caused in animals motor reactions, mainly orienting and negative. Ablation of SMC (field 4,6) caused an increase of positive reactions to sound, including also orienting reactions. A selective character of the reaction to SAS of agonistic type was revealed in animals with "true" aggression to combined (acoustic and subthreshold electric) stimulation. In animals with "false" aggression the combined stimulation caused only nonspecific elements of motor reactions and agonistic vocalizations. SMC ablation caused an increase of aggressive reactions to combined stimulation, revealed in the form of tendency for all animals. In this case in animals with "true" aggression after operation the probability increased of the appearance of motor reactions of aggressive type in comparison with agonistic vocalizations.     

Hypothalamic modulation of baroreceptor inhibition of the electrical activity in the renal nerve

Changes in the renal nerve sympathetic activity in response to electrical stimulation of posterior hypothalamus and vago-aortic nerve were studied in acute experiments on cats. It was shown that stimulation of certain points in hypothalamus defence area led to the suppression of baroreceptor reflex-mediated inhibition of the renal nerve sympathetic activity. Chloralosa depressed hypothalamic modulation of baroreceptor reflexes.     

Mechanisms of central regulation of blood sugar content]

Acute experiments were conducted on adult cats. Injection of insulin microdose (0.025 U/kg with 0.025 ml of saline) into the posterior hypothalamic nucleus caused an increase in the blood sugar level 10 and 70 min after the injection. Changes of the blood sugar level correlated with the EEG activation of the posterior hypothalamic nucleus in response to the insulin injection, spreading to the lateral hypothalamus. However, hormonal stimulation of the posterior hypothalamic nucleus against the background of bilateral coagulation of the lateral hypothalamus produced no increase in the blood sugar level in 10 min. This is indicative of the participation of the lateral hypothalamus in the realization of hyperglycemic reactions in response to the insulin injection into the posterior hypothalamic nucleus.     

Effects of pressure stimulation of the body surface on placing reactions

The effects of pressure stimulation of the body surface on placing reactions were investigated in intact unanesthetized cats. A slight contact applied to the dorsum of the fore- and hindpaws produced the typical placing reactions in these preparations. These reflexes, however, became more prominent if, in addition to the exteroceptive input, a proprioceptive input was elicited after plantar flexion of the paws. Slight pressure applied to the upper part of the body greatly depressed not only tactile placing reactions, but also to a lesser extent proprioceptive placing reactions. Moreover, these reflexes were less prominent and more sluggish and fatiguable than in the normal cats. The depression of the placing reactions elicited by the cutaneous input during pressure applied to the body surface mainly affected the forelimbs. However, as soon as the pressure stimulation was removed, the placing reactions reappeared or became as prominent as usual. We postulate that the exteroceptive input resulting from body pressure decreased the placing reactions by exciting the Purkinje cells of the intermediate cortex of the cerebellum, which are in turn inhibitory on the interpositus nucleus, thus reducing the neuronal discharge of the interpositorubrospinal pathway acting on flexor motoneurons.     

The distribution pattern of alpha-MSH-like immunoreactivity in the cat central nervous system

The distribution pattern of alpha-melanocyte stimulating hormone-like immunoreactivity (alpha-MSH-Li) was studied in cats using avidin-biotin modification of immunocytochemical method. Cell bodies containing alpha-MSH-Li were observed in the medial basal hypothalamus, especially in the infundibular nucleus, the lateral hypothalamus and near zona incerta. Fibers with alpha-MSH-Li extended beyond the hypothalamus, into the paraventricular nucleus of the thalamus, rostral amygdala, periaqueductal gray, locus ceruleus, parabrachial nucleus and medial nucleus of the nucleus tractus solitarius. Axons with alpha-MSH-Li were also seen diffusely in various cortical areas, but more extensively in the limbic cortical regions. The distribution pattern of the cell bodies and fibers containing alpha-MSH-Li bears several similarities to that seen in rats, but differs in that the alpha-MSH-Li was not observed in cell bodies in locations other than the medial basal and lateral hypothalamus.     

Mechanisms underlying inhibition of nociceptive jaw-opening reflex produced by stimulating limbic structures

The comparative effectiveness of the inhibitory influence of tetanic (100 Hz) stimulation of the hypothalamus, amygdala, and limbic cortex on electromyograph (EMG) response in m. digastricus produced by electrical stimulation of tooth pulp afferents was investigated in cats anesthetized by a mixture of chloralose and Nembutal. It was found that the most pronounced inhibition of nociceptive EMG response was produced by stimulating the medial and lateral structures of the hypothalamus, a less intense response by stimulating central and medial amygdaloid nuclei, and the least reaction by stimulation of different areas of the limbic cortex. It was shown that mechanisms underlying inhibition of the jaw-opening reflex produced by hypothalamic tetanic stimulation is unconnected with the concomitant increase in blood pressure. The inhibitory action of hypothalamic tetanic stimulation following blood pressure stabilization persists; this would suggest a primary but not baroafferent mechanism underlying inhibition of activity in trigeminal nucleus nociceptive neurons. Pronounced and protracted depression of jaw-opening reflex takes place following long-term pressor response produced by injecting noradrenaline intravenously. The same pronounced and protracted pressor response occurs under the effects of angiotensin but without any noticeable change in the amplitude of nociceptive EMG response. Hypothalamic and noradrenergic mechanisms of pain sensitivity are discussed.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 19, No. 6, pp. 825–832, November–December, 1987.     

The mechanisms of the influence of the anterior and posterior hypothalamus on the electrical activity of the large hemispheres of the forebrain and on autonomic reactions in hens

Studies have been made of the effect of stimulation of the anterior and posterior hypothalamus on the electrical activity of the hemispheres, arterial blood pressure, heart and respiration rates. Mainly desynchronizing mechanisms were revealed in the ascending influences from both the anterior and posterior hypothalamus. Concerning the descending influences, it was found that stimulation of the anterior hypothalamus evokes depressor reactions, whereas stimulation of the posterior hypothalamus results in pressor reactions. Peculiarities of evolutionary development of the ascending and descending mechanisms of the posterior and anterior hypothalamus are discussed.     

Intralimbic evoked potentials in the formation of an instrumental food conditioned reflex to hippocampal electrostimulation in dogs]

In dogs with the electrodes implanted in the hippocampus, amygdala, septum and hypothalamus an instrumental alimentary conditioned reflex (CR) was elaborated to electrostimulation of the hippocampus. Intralimbic evoked potentials (EPs) were studied during the elaboration and extinction of this reflex and during stimulations of limbic structures conducted with the purpose of CR generalization checking. Late EP components in the lateral hypothalamus and central nucleus of the amygdala changed during CR elaboration and extinction and in the hippocampus during amygdala testing. In both cases the amplitude of trace positivity and of slow negative wave was less, when during stimulation of the structure an instrumental movement was initiated than at its absence.     

Local and distributed neuronal networks and individuality

To estimate stable behavioural peculiarities, an individual varying choice of greater or better appetite reinforcement depending on the time of instrumental motor response was used with cats. A decisive role in realisation of the response choice is played by the influence of motivational structures of hypothalamus and amygdala on formal areas of neocortex typical for "impulsive" (fast reacting) cats, and interaction of the frontal cortex--hippocampus system for the animals with delayed pressing of the lever to obtain their preferred food, i.e. manifesting the ability of "self-control".     

Participation of the posterior hypothalamus in the activity of the ascending activating system]

In chronic experiments on cats with premezencaphalic section of the brain stem electrica stimulation of the posterior hypothalamus caused desynchronization of the electrical activity of the neocortex. After the isolated injury of the posterior hypothalamus a moderate electrical stimulation of the medical part of the midbrain reticular formation failed to cause any pronounced activation of the neocortex. The results obtained indicated an important role of the posterior hypothalamus in the function of the ascending activating system.     

Analysis of the effect of increasing electrodermal stimulation on the somatovegetative reactions evoked by stimulation of the ventromedial hypothalamus

The influence of increasing electrodermal stimulation (EDS) on the dynamics of the somatovegetative reactions evoked by electrical stimulation of negative emotiogenic regions of the hypothalamus was studied. EDS produced a blocking effect on the somatovegetative reactions evoked by stimulation of the ventromedial hypothalamus (VMH). Pretreatment with naloxone prevented the effects of EDS. Injection of beta-endorphine in a dose of 10 micrograms to the lateral ventricules of the animal brain also blocked the somatovegetative reactions during VMH stimulation. Injection of beta-endorphine in doses of 50-100 micrograms enhanced and prolonged the somatovegetative reactions evoked by VMH stimulation. Elevated arterial blood pressure, pronounced bradycardia, extrasystoles, muscle tremor, and pathologic respiration were recorded. These disorders were completely reversed by EDS. It is assumed that both opiate peptides and their receptors are involved in the mechanism of the somatovegetative reactions evoked by VMH stimulation, experiencing the influence of EDS.     

Functional relations between limbic structures during initiation of seizure activity

It was shown by the technique of conditioned-reflex activation of a functional epileptogenic focus that seizure activity in response to a conditioning stimulus in rabbits and cats arises exclusively in the hippocampus, even if the epileptogenic focus is created by electrical stimulation of the septum or amygdala. During stimulation of the hippocampus itself, "spontaneous" reactivation of seizure activity took place, but in response to the conditioning stimulus only an increase in the frequency and strength of the spontaneous epileptiform activity was observed. Conditioned-reflex seizure activity was much more marked in rabbits than in cats. After bilateral electrolytic injury to the septal region no marked seizure activity was observed in rabbits in response to a conditioning stimulus. In that case there was only an increase in the frequency of spontaneous epileptiform activity in the hippocampus. It is concluded that the hippocampus, with its synchronizing function, can perform the role of initiator of seizure activity, and the functional link between the septum and hippocampus brings about its final synchronization.     

Angiotensin II in the mechanisms of hypothalamic pressor reactions

The influence of intracerebroventricular injections of the angiotensin II antagonist--saralasin on the cardiovascular reactions elicited by electrical stimulation of different structures of the hypothalamus in rabbit was studied. The saralasin in doses from 1 to 1.5 mg reduced arterial pressure by 9 +/- 0.2 mm Hg and decreased the amplitude of the hypertensive reactions elicited by electrical stimulation of the paraventricular, supraoptic, ventromedial, supramammillary nucleus of the hypothalamus, area hypothalamic anterior and lateral. It has been shown that most suppressing influence of the saralasin on amplitude of the hypertensive reactions elicited by electrical stimulation of the paraventricular (68%) and supraoptic (76%) nucleus of the hypothalamus which contain magnocellular neurosecretory neurons.     

The effect of ablation of the caudate nucleus on the alimentary zone of the lateral hypothalamus]

A conditioned food-procuring reaction previously elaborated to an acoustic stimulus was reproduced in chronic experiments on six cats by means of direct electrical stimulation of the posterior parts of the lateral hypothalamus. Folloiwng extensive bilateral electrolytic ablation of the caudate nucleus, conditioned food-procuring reaction to the stimulation of the hypothalamus could not be reproduced for 40 to 70 days. The conditioned foor-procuring reflex to the acoustic stimulus disappeared for 14 to 30 days to be subsequently spontaneously restored. After caudatotomy, a diminution of the average amplitude of background oscillations and of evoked potentials to acoustic stimuli was recorced in the examined zones of the lateral hypothalamus. The part played by the caudate nucleus in the processes of alimentary behaviour activation is discussed.