A quantitative comparison of the hominoid thalamus: II. Limbic nuclei anterior principalis and lateralis dorsalis

Structures in the limbic system are commonly thought to be similar in form and function in all mammalian brains. In the study reported here, two thalamic limbic nuclei, N. anterior principles and N. lateralis dorsalis, were compared among a group of extant of extant hominoids. The nuclear volumes, neuronal densities, number of neurons per nucleus, and volumes of neuronal perikarya were measured. Humans have much larger nuclei but the nuclei constitute a similar proportion of the whole thalamus as found in the other hominoids. Whereas the human limbic nuclei were observed to have a decrease in the densities of nerve cells compared with those of the other hominoids, this difference is less than that found in most other thalamic nuclei. Consequently the estimated number of neurons is much higher for humans. The total number of neurons best separates the human limbic nuclei from those of the other hominoids. This preliminary study suggests that during hominid evolution neurons were preferentially added to the limbic nuclei of the thalamus.     

Differences in the sensory support of the anterior and posterior sections of the limbic cortex of the rat

Using retrograde axonal transport of horseradish peroxidase, studies have been made on the thalamic projections in the anterior and posterior parts of the limbic cortex with special reference to exterosensory system projections (visual, auditory and somatic). Projections of the retinorecipient nuclei of the anterior hypothalamus and classic thalamic visual relays (n. geniculatus lateralis dorsalis, n. lateralis posterior, pretectum) were found in the anterior and posterior limbic cortex. There are also inputs from the thalamic relays of the auditory (n. geniculatus medialis) and somatic (n. ventralis posterior) systems in the posterior limbic cortex The data obtained indicate: 1) that sensory supply of the limbic cortex in rats may be realized via direct pathways from sensory thalamic relays; 2) that thalamic sensory supply of the anterior limbic cortex differs from that of the posterior one. In the former, projections of the thalamic relays of the visual, auditory and somatic systems were found, whereas in the posterior cortex only visual system is presented. Topographic organization of the thalamic nuclear areas sending afferents to the anterior limbic cortex differs from that of the posterior limbic cortex.     

Connections between the anterior thalamic nuclei in turtles (data of the peroxidase method)

It turtles, Testudo horsfieldi (Gray) connections of anterior dorsomedial and dorsolateral thalamic nuclei have been investigated by means of horseradish peroxidase, injected ionophoretically. Retrogradely labelled neurons are predominantly revealed ipsilaterally in the cerebral structures belonging to the limbic system: in the forebrain--basal parts of the hemisphere, septum, adjoining nucleus, nuclei of the anterior and hippocampal commissures, hippocampal cortex, preoptic area; in the diencephalon--in the subthalamus (suprapeduncular nucleus), in some hypothalamic structures (para- and periventricular nuclei, posterior nucleus, lateral hypothalamic area, mamillary complex); in the brain stem--ventral tegmental area, superior nucleus of the suture. Less vast connections are with nonlimbic cerebral formations: projections to the striatum, afferents from the laminar nucleus of the acoustic torus, nuclei of the posterior commissure. Similarity and difference of the nuclei investigated in the turtles with the thalamic anterior nuclei in lizards, with the anterior and intralaminar nuclei in Mammalia are discussed. An idea is suggested on functional heterogeneity of the anterior nuclei in reptiles and on their role for ensuring limbic functions at the thalamic level.     

Impairments of thalamic nuclei in idiopathic generalized epilepsy revealed by a study combining morphological and functional connectivity MRI

Objective

Neuroimaging evidence suggested that the thalamic nuclei may play different roles in the progress of idiopathic generalized epilepsy (IGE). This study aimed to demonstrate the alterations in morphometry and functional connectivity in the thalamic nuclei in IGE.

Methods

Fifty-two patients with IGE characterized by generalized tonic-clonic seizures and 67 healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted MRI data were acquired for voxel-based morphometry (VBM) analysis, and resting-state blood-oxygenation level functional MRI data were acquired for functional connectivity analysis. The thalamic nuclei of bilateral medial dorsal nucleus (MDN) and pulvinar, as detected with decreased gray matter volumes in patients with IGE through VBM analysis, were selected as seed regions for functional connectivity analysis.

Results

Different alteration patterns were found in functional connectivity of the thalamic nuclei with decreased gray matter volumes in IGE. Seeding at the MDN, decreased connectivity in the bilateral orbital frontal cortex, caudate nucleus, putamen and amygdala were found in the patients (P<0.05 with correction). However, seeding at the pulvinar, no significant alteration of functional connectivity was found in the patients (P<0.05 with correction).

Conclusions

Some specific impairment of thalamic nuclei in IGE was identified using morphological and functional connectivity MRI approaches. These findings may strongly support the different involvement of the thalamocortical networks in IGE.     

Is the "nonspecific" thalamus still "nonspecific"?

The classical concept of "nonspecific" thalamus, as distinguished from the principal thalamic nuclei (i.e. the primary sensory, motor and limbic relays) is here briefly revisited in the light of anatomical investigations performed in the last decades, and primarily those based on tract tracing techniques. Altogether these data pointed out that the so-called "nonspecific" thalamus is composed by a heterogeneous collection of nuclear masses, which display not only species differences, but also marked internuclear variations in their cytological and neurochemical features, connections, areal and laminar distribution upon the cortex, and functional properties. Thus, the "nonspecific" thalamus exerts a modulatory role on cortical activity, chiefly regulated at the intrathalamic level by the interplay between the thalamic reticular nucleus and the interneurons and projection neurons of the dorsal thalamus. However, each of the components that have been traditionally considered as "nonspecific" also subserves selective roles in the transfer of different kinds of information from the thalamus to the cerebral cortex and basal ganglia.     

Effect of electric stimulation of cortical portions of the limbic system on the activity of neurons of the anterior thalamic nuclei in the rabbit

Effects of electrical stimulation of the subiculum (SB) and posterior limbic cortex (PLC) were studied extracellularly in the anteroventral (AV) and anterodorsal (AD) limbic thalamic nuclei of awake chronic rabbits. Stimulation of SB and PLC evoked in some AV neurones discharges of 1-2 spikes. Gradual potentiation and low frequency of following (up to 10-15 Hz) were characteristic of these responses. Activity of the majority of AV cells was suppressed by stimulation with appearance of inactivation bursts, "neuronal spindles" and modulation on delta-frequencies. Spike responses were evoked by SB and (rarely) by PLC stimulation only in a certain class of AD neurones which tentatively are regarded as relay cells. The neurones with high-frequency, low-amplitude discharges (putative inhibitory interneurones) reacted to stimulation of PLC and to a lesser extent of SB by prolonged series of spikes (150 ms--2s). Stimulation of PLC exerted prolonged influence upon neuronal responses to sensory stimuli.     

Role of the basal ganglia in the occurrence of paradoxical sleep dreams (hypothetical mechanism)

A hypothetical mechanism of the basal ganglia involvement in the occurrence of paradoxical sleep dreams and rapid eye movements is proposed. According to this mechanism, paradoxical sleep is provided by facilitation of activation of cholinergic neurons in the pedunculopontine nucleus as a result of suppression of their inhibition from the output basal ganglia nuclei. This disinhibition is promoted by activation of dopaminergic cells by pedunculopontine neurons, subsequent rise in dopamine concentration in the input basal ganglia structure. striatum, and modulation of the efficacy of cortico-striatal inputs. In the absence of signals from retina, a disinhibition of neurons in the pedunculopontine nucleus and superior colliculus allows them to excite neurons in the lateral geniculate body and other thalamic nuclei projecting to the primary and higher visual cortical areas, prefrontal cortex and back into the striatum. Dreams as visual images and "motor hallucinations" are the result of an increase in activity of definitely selected groups of thalamic and neocortical neurons. This selection is caused by modifiable action of dopamine on long-term changes in the efficacy of synaptic transmission during circulation of signals in closed interconnected loops, each of which includes one of the visual cortical areas (motor cortex), one of the thalamic nuclei, limbic and one of the visual areas (motor area) of the basal ganglia. pedunculopontine nucleus, and superior colliculus. Simultaneous modification and modulation of synapses in diverse units of neuronal loops is provided by PGO waves. Disinhibition of superioir colliculus neurons and their excitation by pedunculopontine nucleus lead to an appearance of rapid eye movements during paradoxical sleep.     

Connections between presumed diencephalic nuclei of the lizard limbic system using horseradish peroxidase axonal transport technique

Connections between the anterior thalamic and habenular nuclei were investigated in the lizard by administering horseradish peroxidase to these nuclei. They were shown to have overlapping locations of afferent sources, namely basotelencephalic structures, nuclei of anterior and hippocampal commissures, preoptic and lateral hypothalamic area, and superior raphe nucleus, as well as common projection zones, viz: the mamillary complex and the ventral tegmental area. Specific connections confined to individual nuclei were discovered, apart from those common to the nuclei: A reciprocal connection with the dorsolateral hypothalamic nucleus (for the anterior dorsolateral nucleus), a projection to the interpeduncular nucleus (for the habenular nucleus), and to the dorsal hypothalamic area (for the dorsomedial nucleus). No sources of afferent pathways to the anterior thalamic nuclei were found in the mamillary complex. All the thalamic nuclei studied, togetherwith their connections, are considered diencephalic relay links in pathways comparable with the dorsal (in the case of the habenular nuclei) and the ventral (with respect to the anterior thalamic nuclei) pathways of the mammalian limbic system.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 19, No. 1, pp. 110–120, January–February, 1987.     

Central neural mechanisms that interrelate sensory and affective dimensions of pain

The perception of pain is highly complex, and requires neural integration from a variety of routes. Spinal pathways to the amygdala, hypothalamus, reticular formation, medial thalamic nuclei, and limbic cortical structures transmit information involved arousal, bodily regulation, and emotional responses. Other, albeit indirect, pathways can carry signals to these same structures, for example, from spinal pathways to somatosensory thalamic and cortical areas, and from these to cortical limbic structures. Indirect cortico-limbic pathways integrate nociception with information about the status of the body and indirect routes must culminate in the prioritization of emotions and responses to pain.     

The effect of bilateral amygdaloid nucleus lesions on rat small bowel crypt cell kinetics

Previous investigators have found that central nervous system lesions, in particular lesions of the hypothalamus, may increase the crypt cell mitotic rate in the rat small bowel. Since the amygdaloid nuclei form part of the limbic system (the "visceral brain") and have functional neural connections with the hypothalamus the effect of bilateral electrocoagulation lesions of the amygdaloid nuclei on crypt cell mitotic rate in the rat small bowel was investigated, using a stathmokinetic technique. Bilateral amygdaloid lesions were found to be associated with a marked increase in crypt cell mitotic rate in the proximal jejunum and distal ileum. Consideration of the neural connections of the amygdaloid nuclei suggests that these effects may possibly be mediated via the hypothalamus and the autonomic nervous system. The effects of lesions of other parts of the limbic system on crypt cell mitotic rate will be published subsequently.     

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.     

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.     

A role of the basal ganglia in the occurrence of visual hallucinations (a hypothetical mechanism)

A hypothetical mechanism of the basal ganglia involvement in visual hallucinations is proposed. According to this mechanism, hallucination is the result of modulation of the efficacy of corticostriatal synaptic inputs and changes in spiny cell activity due to the rise of striatal dopamine concentration (or due to other reasons). These changes cause an inhibition of neurons in the substantia nigra pars reticulata and subsequent disinhibition of neurons in the superior colliculus and pedunculopontine nucleus (including its cholinergic cells). In the absence of afferentation from the retina this disinhibition leads to activation of neurons in the lateral geniculate nucleus, pulvinar and other thalamic nuclei projecting to the primary and highest visual cortical areas, prefrontal cortex, and also back to the striatum. Hallucinations as conscious visual patterns are the result of selection of signals circulating in several interconnected loops each of which includes one of above mentioned neocortical areas, one of thalamic nuclei, limbic and one of visual areas of the basal ganglia, superior colliculus and/or pedunculopontine nucleus. According to our model, cannabinoids, opioids and ketamine may lead to hallucinations due to their promotional role in the LTD of cortical inputs to GABAergic spiny cells of striatal striosomes projecting to dopaminergic neurons, disinhibition of the lasts, and increase in striatal dopamine concentration.     

Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show deficient respiratory and cardiac responses to hypoxia and hypercapnia, despite apparently intact arousal responses to hypercapnia and adequate respiratory motor mechanisms, thus providing a model to evaluate functioning of particular brain mechanisms underlying breathing. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals, corrected for global signal changes, and evaluated them with cluster and volume-of-interest procedures, during a baseline and 2-min hypoxic (15% O(2), 85% N(2)) challenge in 14 CCHS and 14 age- and gender-matched control subjects. Hypoxia elicited significant (P < 0.05) differences in magnitude and timing of responses between groups in cerebellar cortex and deep nuclei, posterior thalamic structures, limbic areas (including the insula, amygdala, ventral anterior thalamus, and right hippocampus), dorsal and ventral midbrain, caudate, claustrum, and putamen. Deficient responses to hypoxia included no, or late, changes in CCHS patients with declining signals in control subjects, a falling signal in CCHS patients with no change in controls, or absent early transient responses in CCHS. Hypoxia resulted in signal declines but no group differences in hypothalamic and dorsal medullary areas, the latter being a target for PHOX2B, mutations of which occur in the syndrome. The findings extend previously identified posterior thalamic, midbrain, and cerebellar roles for normal mediation of hypoxia found in animal fetal and adult preparations and suggest significant participation of limbic structures in responding to hypoxic challenges, which likely include cardiovascular and air-hunger components. Failing structures in CCHS include areas additional to those associated with PHOX2B expression and chemoreceptor sites.     

Organization of the thalamic and cortical projections of the cat neostriatum]

The investigation has demonstrated that in the cat the nucleus caudatus and the putamen are projected on the cortex and thalamic nuclei of the ipsilateral hemisphere according to a certain topical principle characterized by both similarity in localization of projections of these two structures of the neostriatum and their difference. On the one hand, to the same fields of the cortex and the thalamic nuclei fibres from both structures of the neostriatum go, and on the other hand--a number of cortical zones and thalamic nuclei get projections either from the nucleus caudatus or from the putamen only. Owing to a certain organization of the connections studied, it is possible to consider them as the base of functional heterogeneity of the basal ganglia. Over-lapping of the cortical and thalamic projections of the nucleus caudatus and the putamen might explain common striatal effects on behavioral reactions.     

Functional architectonics of neuronal antinociceptive mechanisms during the electroacupuncture method of reflex action

The peculiarities of neurone bioelectric activity of sensory thalamic nuclei under electroacupuncture (EAP) stimulation have been studied in acute experiments on cats. EAP stimulation has been established to change spontaneous and evoked activity of neurones of sensory thalamic nuclei, that testifies to the development of a new functional state. The functional state of the cortex, in particular the second somatosensory region has been shown to determine the nature of neurone activation of sensory thalamic nuclei during the EAP stimulation. Schemes of possible organization of functional pools realizing the mechanisms of inhibition of nociceptive signals on central neurones during EAP way of reflex stimulation are suggested.     

Electrophysiologic and behavioral changes after destruction of the basolateral nucleus of the amygdala in the rat

In experiments on rats the influence was studied of unilateral destruction of the basolateral amygdala on heterogeneous conditioned reflexes and focal potentials (FPs) of the dorso-medial thalamic nucleus, elicited by stimulation of the peri-amygdalar cortex. It is shown that reduction during 3-4 postsurgery weeks of the number of goal-directed reactions and increase of their latencies are accompanied by suppression of the evoked activity, testifying to disturbance of functional interaction between the structures of limbic and thalamic levels. Changes of FPs parameters, reflecting the establishment of new functional interrelations between the centres of the lesioned system excelled in duration compensatory restoration of properties of conditioned reflexes.     

A quantitative comparison of the hominoid thalamus: III. A motor substrate—the ventrolateral complex

Nuclear volumes, nerve cell densities, numbers of neurons, and volumes of nerve cell perikarya of the thalamic ventrolateral complex (VL), a neural substrate for movement, were measured in specimens from two gibbons, one gorilla, one chimpanzee, and three humans, and the values were compared. The human VL had about one-and-a-half times as many neurons as did those of the great apes. The relative frequencies of the sizes of nerve cell perikarya differed slightly in the ventrolateral segment of VL; no differences were noted in the rest of VL. Compared with findings from other parts of the thalamus, the differences in the volumes of VL were greater than those found in the thalamic sensory nuclei, similar to those of rest of the thalamus, and less than those found in the whole brain. The increased number of neurons in human VL was similar to that of the somatosensory relay complex, but greater than those of the auditory and visual nuclei and less than those of the limbic and association nuclei. In human evolution, the numbers of neurons in the VL appeared to increase at a faster rate than did neurons of the pyramidal tract, whereas the motor cortex apparently increased at a rate greater than VL.     

Analysis of the effects of electrical stimulation of certain limbic structures

It has been established that stimulation of the structures of the limbic system (hippocampus, amygdaloid complex, septum) and the medial nucleic of the thalamus of rabbits in conditions of free behavior elicits four basic types of behavioral reactions: arousal, orientation-investigatory, aggressive-defensive and various epileptiform (convulsive) reactions. Activation of behavior, i.e., arousal and the orientation-investigatory reaction, constantly appear on stimulation of the unspecific thalamic nuclei. The aggressive-defense reaction is elicited by stimulating the nuclei of the amygdaloid complex of the ventral part of the hippocampus and the ventromedial nuclei of the thalamus. The epileptiform reactions are most readily reproduced on stimulation of the amygdaloid complex and the ventral part of the hippocampus. The threshold for the appearance of discharges of the aftereffect is very low. The latter are more sustained on stimulation of the basolateral part of the amygdala and the ventral part of the hippocampus. In rabbits as compared with higher animals the discharges on stimulation rapidly spread not only to the limbic system but also to the reticular formation and the neocortex.Kharkov Medical Institute. Translated from Neirofiziologiya, Vol. 1, No. 2, pp. 194–201, September–October, 1969.