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.     

Background activity of neurones of the amygdaloid complex and its changes in response to hippocampal stimulation

The background activity of neurones of the amygdaloid complex (AC) and changes induced in it by stimulation of the fimbria and adjacent regions of the hippocampus were recorded by means of microelectrodes. Background activity of 40% of the neurones of the AC consisted of an irregular spike discharge, while that of 10% was regular. The remaining neurones showed a tendency to group discharges. High-frequency hippocampal stimulation at 200 pulses/sec inhibited activity of 37% and facilitated activity of 23% of the neurones. Responses began 20–300 msec after the onset of stimulation. Low-frequency stimulation at 0.5–8 pulses/sec facilitated discharges in 42.6% of neurones. The results obtained are discussed in relation to the influence of the hippocampus on AC activity.Institute of Physiology, Siberian Branch of the Academy of Sciences of the USSR, Novosibirsk. Translated from Neirofiziologiya, Vol. 3, No. 5, pp. 500–504, September–October, 1971.     

Generalization of an instrumental defensive conditioned reflex elaborated to electric stimulation of the hypothalamus in dogs

Generalization of defensive conditioned reflexes elaborated to electrical stimulation of the lateral hypothalamus (LH) was studied in four dogs with electrodes implanted in various structures of the limbic system. Electrocutaneous stimulation was switched off when the dog lifted the foreleg to a definite level. Generalization of the conditioned reflex was manifested in different degrees when testing different formations of the limbic system, or testing one and the same structure, but at different stages of conditioning. Two types of generalization were found: the first one--a well pronounced motor reaction, by its latency, level and duration of lifting the foreleg similar to movements appearing in response to the conditioned stimulus; and the second one--low amplitude or short-term movements differing from conditioned ones. The first type of generalization was observed in response to stimulation of LH, contralateral to the point of signal stimulation, of the ventromedial hypothalamic nucleus, the mammillary bodies and the basal, lateral and to a lesser degree, the central nucleus of the amygdaloid complex; the second type--in response to stimulation of the ventral hippocampus, the medial and lateral septum nuclei.     

Responses of the cingulate cortex to dorsal hippocampal stimulation in cats

Responses of the cingulate gyrus to stimulation of the dorsal hippocampus were studied in unanesthetized cats. Both short and long polysynaptic projections were found to participate in their genesis. It is postulated on the basis of the results of experiments with stimulation of and injury to the limbic nuclei of the thalamus that responses of the posterior zone of the cingulate gyrus to dorsal hippocampal stimulation arise as a result of activation of the anteroventral thalamic nucleus.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 13, No. 1, pp. 7–13, January–February, 1981.     

Reactions of neurons of the orbitofrontal cortex to stimulation of optic thalamic nuclei

The reactions of 288 neurons of the orbitofrontal cortex (OFC) to stimulation of the posteroventral (VP), ventral anterior (VA), and reticular (R) nuclei, as well as the median center (CM) of the thalamus, were investigated in acute experiments on cats. OFC neurons can be divided into four groups by their reactions to stimulation of thalamic nuclei: 1) those which respond with an increase in the frequency of the discharges to single and serial stimuli with a frequency of up to 20/sec; 2) those which respond doubtfully to single stimuli with a frequency of 4–12/sec; 3) those which respond with inhibition of the background impulses; 4) those which do not respond to stimulation of the nuclei. Stimulation of the thalamic nuclei evoked responses of OFC neurons with a large scatter of the latent period duration. The responses of neurons to stimulation of the VP (mean latent period 19.1±6.1 msec) had the shortest latent period (sometimes less than 3–4 msec). Reactions with a longer latent period developed upon stimulation of the VA (23.8±7.4 msec) and CM (42.8±12.8 msec). The uniqueness of the links of the OFC with the various optic thalamic nuclei is shown in an analysis of the material obtained and possible methods of the activation of the neurons of this region from thalamic structures are discussed.State Medical Institute, Kemerovo. Translated from Neirofiziologiya, Vol. 3, No. 4, pp. 350–358, July–August, 1971.     

In vitro autoradiographic localization of vasoactive intestinal peptide (VIP) binding sites in the rat central nervous system

This paper describes the autoradiographic distribution of VIP binding sites in the rat central nervous system using monoiodinated ¹²³I-labeled VIP. High densities of VIP binding sites are observed in the granular layer of the dorsal dentate gyrus of the hippocampus, the basolateral amygdaloid nucleus, the dorsolateral and median geniculate nuclei of the thalamus as well as in the ventral part of the hypothalamic dorsomedial nucleus.     

Role of specific and nonspecific thalamic nuclei in the genesis of some slow rhythms of the human electrocorticogram

An electrocorticographic method of recording after-potentials in response to electrical stimulation of the thalamic nuclei in limbic structures during stereotaxic operations was developed. Altogether 42 patients undergoing operations for subcortical hyperkinesia, pain syndromes, and Kozhevnikov's epilepsy were investigated. The character of the cortical after-discharges in response to stimulation of the ventro-oral nuclear complex (V.o.) and the centrum medianum (Ce) of the thalamus and the amygdala differs in its character. These differences affected the area of spread of after-synchronization of the slow rhythms in regions of the hemispheres, the duration of the bursts of after-activity, and the expression of the accompanying autonomic responses. During the after-response to electrical stimulation of V.o. a relatively local after-synchronization of the slow rhythms in the ECoG was observed in the premotor area on the side of stimulation. The off-response to electrical stimulation of Ce, by contrast with V.o. was bilateral synchronization of the slow rhythm, coinciding in some cases with the appearance of bradypnea, bradycardia, and vasomotor and pilomotor responses. The most marked autonomic responses, associated with long volleys of after-hypersynchronization of slow waves or epileptoid discharges, were observed after stimulation of the amygdala. Problems connected with the mechanisms of after-synchronization of the cortical rhythm and the role of the various thalamic and limbic structures in these mechanisms are discussed.N. N. Burdenko Institute of Neurosurgery, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 227–235, May–June, 1973.     

Distribution of horseradish peroxidase-labeled neurons giving rise to descending fiber systems in the basal ganglia and hypothalamus in cats

The distribution of neurons giving rise to various descending fiber systems to brain-stem structures in the basal ganglia (including amygdaloid nuclei) and hypothalamus of the cat was studied by the retrograde axonal transport of horseradish peroxidase method. Neurons in the medial part of the central nucleus and of the magnocellular part of the basal nucleus of the amygdaloid group were shown to send axons to the dorsal hippocampus, substantia nigra, lateral part of the central gray matter, and the mesencephalalic reticular formation and also to the region of the locus coeruleus and the lateral medullary reticular formation at the level of the inferior olives. The predominant source of projections to the hypothalamus and brainstem structures is the central amygdaloid nucleus, which also sends projections to the nucleus of the tractus solitarius, the dorsal motor nucleus of the vagus nerve, and the superior cervical segments of the spinal cord. Uncrossed fiber systems descending from the basal ganglia terminate at the level of the pons, whereas uncrossed and crossed fiber systems descending from the dorsal and ventromedial hypothalamus can be traced into the spinal cord. The possible role of nuclei of the amygdaloid group, the hypothalamus, and their efferent projections in the regulation of somatic and vegetative functions and also of complex behavioral reactions is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 13, No. 1, pp. 14–23, January–February, 1981.     

Single unit responses of the reticular and ventral anterior nuclei of the thalamus to electrical stimulation of the centrum medianum

In acute experiments on cats anesthetized with thiopental (30–40 mg/kg, intraperitoneally) and immobilized with D-tubocurarine (1 mg/kg) responses of 145 neurons of the reticular and 158 neurons of the ventral anterior nuclei of the thalamus to electrical stimulation of the centrum medianum were investigated. An antidromic action potential appeared after a latent period of 0.3–2.0 msec in 4.1% of cells of the reticular nucleus and 4.4% of neurons of the ventral anterior nucleus tested in response to stimulation. The conduction velocity of antidromic excitation along axons of these neurons was 1.7–7.6 m/sec. Neurons responding with an antidromic action potential to stimulation both of the centrum medianum and of other formations were discovered, electrophysiological evidence of the ramification of such an axon. Altogether 53.8% of neurons of the reticular nucleus and 46.9% of neurons of the ventral anterior nucleus responded to stimulation of the centrum medianum by orthodromic excitation. Among neurons excited orthodromically two groups of cells were distinguished: The first group generated a discharge consisting of 6–12 action potentials with a frequency of 130–640 Hz (the duration of discharge did not exceed 60 msec), whereas the second responded with a single action potential. Inhibitory responses were observed in only 0.7% of neurons of the reticular nucleus and 4.4% of the ventral anterior nucleus tested. Afferent influences from the relay nuclei of the thalamus, lateral posterior nucleus, and motor cortex were shown to converge on neurons responding to stimulation of the centrum medianum.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 1, pp. 36–45, January–February, 1980.     

Isocortical Hyperemia and Allocortical Inflammation and Atrophy Following Generalized Convulsive Seizures of Thalamic Origin in the Rat

1. Generalized convulsive seizures can be elicited by a single unilateral microinjection of the cholinergic muscarinic agonist, carbachol, into the specific sites of the thalamus including ventral posterolateral and the reticular thalamic nuclei. The implication of the thalamic specific and reticular neurons is reviewed and discussed.2. On the basis of the c-fos regional expression and well-known efferent and afferent pathways linking these regions, a neuronal network relating the limbic, thalamo–striatal–cortical, and central autonomic systems, was constructed.3. The pattern of Fos immunoreactivity associated with long-lasting isocortical vasodilatation elicited by generalized convulsive seizures in anesthetized rat following cholinergic stimulation of the thalamus can be attributed to both the electrocortical activity and the long-lasting increase in cortical blood flow. We propose that the sustained cerebral cortical blood flow response during convulsive epileptic seizures may implicate intracerebral vasodilatory and vasoconstrictory neural mechanisms. Double-labeled NADPH-d and Fos-positive neurons implicated in maintaining the sustained isocortical vasodilatory response were found in the anterior lateral hypothalamic area. Inhibition of these neurons prevented the increase in cortical blood flow despite an increased metabolic demand manifested by the ictal electrocortical activity.4. Medial temporal lobe atrophy, including hippocampus, amygdala, and parahippocampal gyrus (piriform and entorhinal cortices) are the most common pathology in man. However the origin of medial lobe atrophy remain uncertain. Our results provide evidence that the allocortical microvascular inflammation may be in origin of the neurovascular degenerative processes leading to atrophy.     

Electrophysiological analysis of the organization of somatosensory thalamic inputs in the frog

Potentials produced in the frog thalamus by electrical stimulation of the peripheral nerves were investigated by sink and current source-density analysis. Sinks, which are viewed as potential generation sites, were located in three regions: the cell-free zone of the ventral thalamus adjoining the ventrolateral nucleus, the ventromedial and ventrolateral nuclei, and the caudal section of the dorsal thalamus. Evoked activity was recorded in individual neurons in the area of the second and third of these sinks. The first sink failed to form after section of the dorsal tracks of the spinal cord, while the remaining two only appeared after a considerably extended latency. It is suggested that nuclei of the ventral and caudal sections of the dorsal thalamus receive somatic impulses through the systems connected with the dorsal as well as the ventrolateral columns of the spinal cord. The direct projections of the primordial nuclei of dorsal columns may be involved in afferentation the ventral thalamus.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 687–695, September–October, 1986.     

Afferent connections of the basolateral division of the amygdaloid complex of the cat brain

Injection of horseradish peroxidase into the basal macrocellular and lateral nuclei of the amygdaloid complex (BLAC) in the cat brain has revealed their rich thalamic afferentation. On the BLAC there are massive projections of: a) nuclei of the middle line of the precommissural pole of the dorsal thalamus (anterior parts of the paratenial, interanteromedial and reunial nuclei), as well as the whole anterior paraventricular nucleus, medial part of the ventral posteromedial nucleus; b) postcommissural nuclei of the dorsal thalamus; some "nonacustical" nuclei of the internal geniculate body (ventrolateral nucleus, medial and macrocellular parts and the most caudal end of the internal geniculate body). Rather essential are projections of the "posterior group nuclei", those of the suprageniculate nucleus, of some parts of the ventral thalamus (subparafascicular nucleus, marginal and peripeduncular nuclei) and parabrachial nucleus. Scattered single projections are obtained from all hypothalamic parts (most of all the ventromedial nucleus), reticular nuclei of the septum, substantia innominata, substantia nigra, truncal nuclei of the raphe. Variety of the dorsal thalamic nuclei, sending their fibers to the BLAC reflects variety of sensory information, that gets here, according to its modality, degree of its differentiation and integrity. A number of the dorsal thalamus nuclei, owing to abundance of labelled neurons, can be considered as special relay thalamic nuclei for the BLAC resembling corresponding relay nuclei for the new cortex.     

Frequency potentiation in the neonatal rabbit hippocampus

The formation of properties of frequency potentiation in the entorhinal afferent pathway of the hippocampus was studied in unanesthetized rabbits aged from 1 to 15 days. In areas CA₁ and CA₃ of the dorsal hippocampus in newborn rabbits repetitive (1–20 Hz) electrical stimulation of the perforant path led to an increase in amplitude of the slow wave of the field potential by 20–100% compared with the control and to an increase in the probability of response discharges from the neurons from 0–0.5 in the control to 0.8–1.0 during tetanization. In rabbits aged 2–3 days potentiation was more marked at a frequency of 4–6 Hz, whereas depression of the responses developed rapidly to a higher frequency of stimulation. The frequency optimum of 4–15 Hz was established on the 5th day. Potentiation of the first component of the field potential was observed starting from the 8th–10th day of life. The experimental results show that the property of frequency potentiation in the cortical afferent connections of the hippocampus is found in rabbits actually at birth, and it acquires the adult form at the beginning of the second week of life.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 533–539, November–December, 1979.     

Efferent connections of the centrum medianum of the cat thalamus revealed by autoradiography

Efferent connections of the centrum medianum and parafascicular nucleus of the thalamus (CM-Pf complex) in cats were studied by the method of anterograde axonal transport of tritiated amino acids followed by autoradiography. Projections from CM-Pf ascend to nuclei of the ventral group and nonspecific nuclei of the thalamus, preoptic, dorsal, lateral, and posterior areas of the hypothalamus, and also into the subthalamic region. Descending pathways are formed only by neurons of the caudomedial part of CM-Pf. They project into the pretectal region, superior colliculus, reticular formation, locus coeruleus, region of the ramus communicans, and substantia grisea centralis of the mesencephalon and pons, and also into the nuclei raphe, magnocellular reticular area, and inferior olivary nucleus of the medulla. In agreement with previous observations it was found that the caudomedial part of CM-Pf does not send direct projections into the cortex and striatum.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 224–230, March–April, 1984.     

Ascending projections to the hypothalamus and limbic nuclei from the dorsolateral pontine tegmentum: a biochemical and electron microscopic study.

Axons arising from the dorsolateral pontine tegmentum of the rat were traced in various hypothalamic and limbic nuclei by the electron microscopic degeneration method (0.5-8 day survival times) and by measuring regional norepinephrine (NE) concentrations after 12 days of survival using a radioenzymatic method. Significant reductions (41-85%) in NE contents were observed in the supraoptic, arcuate, basal and lateral amygdaloid nuclei and in the hippocampus 12 days after the bilateral electrolytic lesions of the locus coeruleus. No changes in NE concentrations were observed in the ventromedial, septal, central amygdaloid nuclei, in the median eminence and olfactory tubercle. Parabrachial lesions resulted in a decrease of NE content only in the olfactory tubercle. By means of electron microscopy terminal degeneration was found in the hypothalamic paraventricular, dorsomedial nuclei, in the median eminence, in the bed nucleus of the stria terminalis, in the central, lateral and basal amygdaloid nuclei, in the hippocampus and in the anterior ventral thalamic nucleus.     

Relation between the septal nuclei and the amygdaloid complex of the brain of the cat

By means of retrograde and anterograde transport of horseradish peroxidase method it has been demonstrated in two series of experiments with injecting the enzyme into separate septal nuclei and the amygdaloid complex in cats that most of amygdaloid nuclei (cortico-medial, central and baso-lateral) are reciprocally connected only with two nuclei in the septum: with the nucleus of the diagonal bundle of Broca and with the nucleus of the terminal strip bed. The projections studied are topically organized. The cortico-medial and basal nuclei of the amygdaloid complex are reciprocally connected with the ventral part of the diagonal bundle of Broca and with the terminal strip bed nucleus. The central nucleus of the amygdala has reciprocal projections only with the terminal strip bed nucleus, and with the ventral part of the diagonal bundle of Broca it has only a unilateral connection. On the contrary, the lateral nucleus of the amygdala is reciprocally connected with the ventral part of the diagonal bundle of Broca, and is only projected on the terminal strip bed nucleus without getting any projections from it.     

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.A. M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 358–365, July–August, 1976.     

Histochemical mapping of succinic dehydrogenase and cytochrome oxidase in the diencephalon and basal telencephalic centers of the brain of squirrel monkey (Saimiri sciureus)

Summary The distribution of succinic dehydrogenase (SDA) and cytochrome oxidase (Cy. O) was mapped in the various diencephalic nuclei and basal telencephalic centers of the squirrel monkey brain. Thirty thick formaldehyde fixed serial sections were also studied for the delineation of the various nuclei, but histochemical preparations proved equally useful for this purpose. Strong SDA and Cy. O activity were observed in the habenular, pulvinaris, anterior dorsalis and ventralis, lateralis dorsalis and posterior, and ventral posterior nuclei. The corpus geniculatum laterale and mediale also showed a strong reaction for these enzymes. The nucleus ventralis anterior, which occupies a very large area in the rostral part of the thalamus, showed moderately strong activity in the cellular patches and negligible activity in the thick fiber bundles passing through it. A comparatively weak reaction was observed in the midline thalamic nuclei. The nucleus caudatus and putamen, however, showed very strong SDA/Cy. O activity. The hypothalamic nuclei showed mild Cy. O and moderate SDA reactions, except for the nucleus ventromedialis hypothalami. The latter showed a little stronger enzyme reaction. The fibers of the internal capsule and the anterior commissure showed little SDA and mild Cy. O activity. The various nuclei of the amygdaloid complex showed similar histochemical reactions with moderate SDA and mild Cy. O activity.This work has been carried out with the aid of Grant No. 00165 from the Animal Resources Branch, National Institutes of Health, and a grant from the National Foundation for Neuro-Muscular Diseases and Nasa Grant NGR-11-001-016.     

Time dependent changes in the concentrations of immunoreactives cholecystokinin octapeptide sulfate in rat brain regions after systemic injection of picrotoxin

Cholecystokinin octapeptide sulfate-like immunoreactivity (CCK-8S-LI) was determined by enzyme linked immunoassay (ELISA) in seven rat brain areas following injections subcutanously of the Cl^- channel blocker, picrotoxin. Time dependent changes in the concentrations of CCK-8S-LI were seen in the hippocampus, amygdaloid complex, septum, and hypothalamus at 15–180 min after the injection. Concentrations of CCK-8S-LI in the frontal cortex, striatum, and thalamus did not show significant changes. CCK-8S-LI in the amygdaloid complex and hypothalamus was the lowest concentrations at 60 min, and the concentrations in the hippocampus and septum were the lowest at 180 min. The data on high-performance liquid chromatography of the extracts from rat amygdaloid complex showed that changes in the concentrations of CCK-8S-LI were mainly due to the concentration of CCK-8S itself. These data indicate that systemic injection of picrotoxin decreases the concentration of CCK-8S in the brain regions, and the decreases in the amygdaloid complex and hypothalamus occur earlier than that in the hippocampus and septum.     

Epileptiform activity in rat hippocampal slices isolated after local septal lesioning by ibotenic acid

In surviving slices of rat hippocampus, isolated from 1 to 4 weeks after septal lesioning by ibotenic acid, extracellular and intracellular responses were recorded in region CA₃. Spontaneous and evoked epileptiform focal discharges are described, synchronous with paroxysmal depolarization shifts (PDS) of the membrane potential and with burst activity of cells. It is shown that the development of synchronized population reactions and PDS have an "all or nothing" character. The values of the resting potential and input resistance of the neurons did not differ significantly from those of cells in the control group of slices. Histological analysis showed destruction of neurons in the dorsal part of the septum, with cells of the medial septum being unaffected. The role of intraseptal mechanisms in the generation of epileptiform activity in region CA₃ of hippocampal slices is discussed.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Department of Physiology and Biochemistry, University of Pisa, Italy. Translated from Neirofiziologiya, Vol. 23, No. 5, pp. 556–564, September–October, 1991.