The role of neuromediators and proteins in genetic and functional organization of animal brain

It was shown that animals that differ in behavioral characteristics (August and Wistar rats) also differ in neurotransmitter and protein metabolism, which can be considered as tests that adequately reflect the functional condition of the central nervous system. These differences are expressed at the level of both subcortical structures (hippocampus and caudate nucleus) and various morphofunctional types of the sensorimotor cortex neurons (layers III and V). Studies on genetically different animals strains have revealed metabolic features that allow determination of individual behavioral features and estimation of individual brain structures in these processes.     

The Role of Neurotransmitters and Proteins in the Genetic-Functional Organization of the Animal Brain

It was shown that animals that differ in behavioral characteristics (August and Wistar rats) also differ in neurotransmitter and protein metabolism, which can be considered as tests that adequately reflect the functional condition of the central nervous system. These differences are expressed at the level of both subcortical structures (the hippocampus and caudate nucleus) and various morphofunctional types of the sensorimotor cortex neurons (layers III and V). Studies on genetically different animals strains have revealed metabolic features that allow the determination of individual behavioral features and an estimation of individual brain structures in these processes.     

Conditioned reflex analysis of functional connections between the hippocampus and limbic system structures

Instrumental defensive conditioned reflex elaborated in dogs to stimulation of the dorsal and ventral hippocampus, also appeared, due to generalization, in response to stimulation of a number of limbic structures. Two types of changes in the generalization effects (estimated by parameters of motor conditioned reaction) were observed in the course of conditioned reflex stabilization: enhancement (in response to stimulation of the lateral hypothalamus, lateral nucleus of septum, limbic cortex) and weakening toward complete disappearance (in response to stimulation of the medial nucleus of amygdala and medial hypothalamus). Manifestation of the generalization phenomenon from the brain structures, which are not involved initially into conditioned activity, suggests the existence of close functional connections between these structures and the hippocampus.     

Correlation between bioelectrical processes of the cortex, thalamus, midbrain reticular formation during formation of a defensive conditioned reflex in rabbits]

EEG power spectra of the sensorimotor area of the neocortex, the dorsal hippocampus, midbrain reticular formation and anteroventral thalamic nucleus, as well as corresponding coherence functions and phase spectra, undergo changes during formation and performance of defensive conditioned reflex in rabbit. The conclusion is draen that in the process of conditioning a morphofunctional system of brain structures is established including the above mentioned formations. Their functional integration occurs on the basis of theta-rhythm. The execution of a conditioned act requires isorhythmicity of electrical processes within the theta-range in the studied structures and an adequate level of their excitability, which is manifested in the dominance of 6,0 c/s frequency.     

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.     

Change in the functional significance of structures of the cat brain as a result of reorganization of its activity

A study was carried out on 8 adult cats of functional role of the frontal, parietal and occipital parts of the neocortex, and also of the dorsal hippocampus, mediodorsal thalamic nucleus and caudate nucleus head, in realization of a delayed spatial choice (DSCh) before and after compensatory reorganizations of the brain activity caused by multiple electrical stimulation of the frontal part of the cerebral cortex. Compensatory reorganization led to a change of functional significance of these structures. While before this change the frontal cortex, hippocampus and mediodorsal thalamic nucleus were critically necessary brain areas for the realization of the DSCh, after it parietal and occipital cortical areas acquired such significance. The obtained data are discussed proceeding from the principle of the integrity in the brain activity.     

The effect of etimizol on the excitability and spontaneous super-slow activity of the structures of the rabbit brain]

Spontaneous superslow electrical brain activity and its changes were studied in acute experiments on curarized rabbits after administration of etimysol in doses of 1.0, 1.5 and 2.5 mg/kg. The effect of the drug persisted for three hours. Two oscillation phases were recorded in the medial group of mesencephalic reticular nuclei and the lateral nucleus of the hypothalamus: a short positive phase and a prolonged negative one. In other brain structures only negative waves were recorded. A significant functional rearrangement of correlative connections of brain structures took place in 90 minutes after the drug administration. The factor analysis showed that the most subtle connections were preserved in the neocortex and the dorsal hippocampus.     

Peculiarities of disorders of brain bioelectrical activity spatial-time organization in patients with different consciousness depression after severe head injury

Specific changes of bioelectrical brain activity was found in 27 patients with different level of posttraumatic consciousness depression by the methods of crosscorrelation, coherence and factor analysis of EEG. The changes of activity of morphofunctional systems of intracerebral integrations were revealed partially by decreasing of unspecific activity from brainstem structures reflected with increasing of slow wave activity and decreasing of EEG coherence in alpha- and beta-range. Depression of system organization of interconnections of bioelectrical brain activity in frontal and occipital regions of both hemispheres was also detected, and testified about decreasing of intercortical and thalamocortical brain system action under brain dislocation. The changes of integrative brain system activity, provides interhemispheric interaction, had the specific characted. Our results propose a "facilitation" of activity of system, providing "direct" interhemispheric connections through corpus callosum and other commissural tracts of telencephalon as a sequel of mesodiencephalon structures depression with steady reciprocal, antiphase relations of slow weve activity in symmetrical areas of hemispheres in coma II patients. The data of our research had shown no complete disintegration of system brain activity in coma II patients in spite of consciousness and brainstem reflexes depression.     

Theory of V.A. Dogiel on polymerization and oligomerization as a general integration concept

The theory of V.A. Dogiel on the significance of polymerization and oligomerization processes in the evolution of Protozoa and Metazoa is compared with the paper of I.I. Schmalhausen (1972) on factors and steps of aromorph evolution. Dogiel’s theory is considered as a general integration conception. Four steps are distinguished in the evolution of biological systems: (1) formation of morphofunctional system by units of the lower structural level, (2) polymerization of morphofunctional units of a system, (3) oligomerization of morphofunctional units of system by means of their reduction, uniting, or differentiation, (4) integration and stabilization of a system owing to development of morphofunctional connections between its parts.     

Transient structures of the human fetal brain: subplate, thalamic reticular complex, ganglionic eminence

Morphological features of the subplate, the thalamic reticular complex and the ganglionic eminence, which represent three major transient structures of the human fetal forebrain, are summarized with special reference to their functional roles. The subplate harboring various neuronal types is an outstandingly wide zone subjacent to the cortical plate in the human fetal brain. Within the subplate various cortical afferents establish synaptic contacts for a prolonged period before entering the cortical plate. Therefore, the subplate is regarded as a "waiting compartment" which is required for the formation of mature cortical connections. Next to the thalamic reticular nucleus, within the fibers of internal capsule, the perireticular nucleus is located which has been established as a distinct entity during development. Its various neuronal types express a number of different neuroactive substances. Perinatally, the perireticular nucleus is drastically reduced in size. It is involved in the guidance of corticofugal and thalamocortical fibers. The ganglionic eminence is a conspicuous proliferative area that persists throughout nearly the entire fetal period. In the human fetal brain it extends medially upon the dorsal thalamic nuclei which receive precursor cells from the ganglionic eminence. Postmitotic cells in the marginal zone of the ganglionic eminence serve as an intermediate target for growing axons. On the whole, all three structures establish transient neural circuitries that may be essential for the formation of adult projections. The characteristics of the three transient structures are particularly relevant for developmental neuropathology as these structures may be damaged in disorders that preferentially occur in preterm infants.     

Genetic determination of the neurophysiological mechanisms of the cortico-subcortical integration of bioelectrical activity of the brain

Contribution of genetical factors to neurophysiological mechanisms of cortico-subcortical integration was investigated in 12 pairs of the monozygotic and 5 pairs of dizygotic twins (aged from 18 to 25). In each pair of twins as well as in all 544 unrelated pairs of subjects from both groups, interpairs similarity of the character of the spatial interaction of bioelectrical activity of the neocortex for different combinations of statistical correlations of EEG (from 16 monopolar electrodes) was estimated. The data obtained allow to suggest a higher common population invariance and a relatively small hereditary and phenotypic variability of morphofunctional systems, which underlie neurophysiological mechanisms of the brain integration in general. Apparently, the formation of the brain stem and subcortical regulatory structures in the ontogenesis, the structures that play the main role in the realization of system combination of different parts of the brain into united formation, occurs to all individuals according to a single principle since its disturbance can probably affect the fundamental monomorphal features of the species. In turn, one can expect a great interindividual variability of establishing of the intraregional connections of neocortex, the role of genetic and environmental factors in the formation of short and relatively long interactions being complex.     

Characterization of central nervous system structures by magnetic resonance diffusion anisotropy

Diffusion-weighted magnetic resonance imaging (MRI) provides information about tissue water diffusion. Diffusion anisotropy, which can be measured with diffusion tensor MRI, is a quantitative measure of the directional dependence of the diffusion restriction that is introduced by biological structures such as nerve fibers. Diffusion tensor MRI data was obtained in the brain, brain stem, and cervical spinal cord. For each region, scans were performed in four normal volunteers. Fractional anisotropy (FA), an index of diffusion anisotropy, was measured within regions of interest located in the corpus callosum, capsula interna, thalamus, caudate nucleus, putamen, brain cortex, pyramidal tract of the medulla, accessory olivary nucleus, dorsal olivary nucleus, inferior olivary nucleus, spinal white and gray matter. The highest FA value was measured in the corpus callosum (81 +/- 3%). The values of the other areas decreased in the following order: pyramidal tract in the medulla (72 +/- 1%), spinal white matter (65 +/- 4%), capsula interna (62 +/- 3%), accessory olivary nucleus (36 +/- 2%), spinal gray matter (35 +/- 5%), dorsal olivary nucleus in the medulla (29 +/- 2%), thalamus (28 +/- 2%), inferior olivary nucleus (15 +/- 2%), putamen (13 +/- 2%), caudate nucleus (13 +/- 2%), and brain cortex (9 +/- 1%). Our results indicate that the underlying fiber architecture, fiber density, and uniformity of nerve fiber direction affect anisotropy values of the various structures. Characterization of various central nervous system structures with diffusion anisotropy is possible and may be useful to monitor degenerative diseases in the central nervous system.     

The role of cerebral regulatory structures in the formation of human EEG

This article generalizes the results of many years’ studies of the EEG of patients with tumorous lesions in the diencephalic, brainstem, and limbic structures, which fulfill the regulatory function in ensuring integral brain activity. The specific features of the inclusion of individual structures under investigation in the organization of the intra- and interhemispheric relations of cortical biopotentials were demonstrated against the background of diffuse changes in the biopotentials that reflect the systemic character of neurodynamic reorganizations when the regulatory brain structures are involved in the pathological process. This study expands the idea of the predominant functional connection of the diencephalic structures with the right hemisphere and brainstem structures with the left one with determination of the regional specific features of changes in the intrahemispheric EEG coherences. The distinguishing features of intercentral relations when the limbic structures are involved in the pathological process show similarity with the neurodynamic reorganizations in patients with lesions in both diencephalic and (even more so) brainstem structures. Universal elements were detected in the formation of integral adaptive reactions of the brain with lesions in its regulatory structures, which reflects their close functional interaction and makes it possible to consider them the individual links of an integral regulatory system. The study revealed reciprocal changes in various forms of electrical activity, which reflects reciprocation of interaction of individual regulatory structures. This is one of the EEG equivalents of the formation of adaptive-compensatory cerebral reactions. The specificity of influence of the studied regulatory structures are clearly seen in situations of their morphofunctional isolation observed during cerebral coma. In these conditions, when the cortex is functionally inactive, the authors demonstrated the dynamic character of changes in interhemispheric asymmetry, which reflects the dominance of individual links of the regulatory system playing the role of supreme regulator of life support of the body in critical states.     

Features of the morphofunctional state of the organs of the thymico-lymphatic system during various adaptive reactions induced by electric stimulation of emotiogenic structures of the brain

Weak electrical stimulation of emotiogenic brain structures was found to lead to the development of different general non-specific adaptation reactions. Stimulation of nucleus lateralis septi was found to evoke mainly the development of activation reaction, while stimulation of globus pallidum caused primarily the development of training reactions. Stress reactions were considerably less frequent in electrical stimulation of both kinds of structures than in the control. This can be explained by small values of the electrical current applied. Morphofunctional activity of thymus lymphatic system depended not only on the type of non-specific reaction but also on the character of the stimulated emotiogenic structure--the functional activity was higher with the stimulation of nucleus lateralis-septi. However, the functional activity of thymus lymphatic system in rats with globus pallidum stimulation was higher than in control rats that were not subject to any stimulation.     

Mechanism of the generalization of a conditioned reflex elaborated to electrostimulation of the brain in dogs

To study functional connections in the limbic system (LS), a model was used of instrumental alimentary CR, elaborated in response to low-frequency hippocampus electrostimulation with testing of its generalization within the LS. The dependence was established of the generalization on activation of corresponding pathways between the signal and tested brain structures, the activation of pathways was estimated by EPs recorded in limbic structures in response to hippocampus stimulation (during CR performance), or vice versa (in generalization trials). It turned out that for the appearance of CR generalization, two-way connections between signal and tested brain structures or connections only to the signal structure are more important. One-way connections from the signal structure to tested ones, judging by data, are not important for appearance of the CR generalization in used model of conditioning.     

Connections of brainstem respiratory nuclei studied by the retrograde horseradish peroxidase axon transport method

Intrabulbar connections of respiratory nuclei and the medullary reticular formation and also descending pathways from these structures in the spinal cord were studied by the retrograde horseradish peroxidase axonal transport method in cats. Neurons of the nucleus ambiguus and nucleus retroambigualis (ventral respiratory group) and of the ventrolateral part of the nucleus of the tractus solitarius (dorsal respiratory group) were shown to form direct two-way connections with each other and with the medial region of the medulla. Neurons of the pneumotaxic center send uncrossed axons to the nucleus ambiguus and to the medial medullary reticular formation. Neurons of the contralateral homonymous nucleus and neurons of the nucleus of the tractus solitarius are sources of projections of the locus coeruleus. A well developed system of direct connections was found between neurons of respiratory nuclei of the two halves of the brain. The possible role of these nuclear formations in genesis of the respiratory rhythm and regulation of the respiratory and other motor functions of the reticular formation is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 149–157, March–April, 1982.     

Neurochemical Organization and Connections of the Cerebral Preglomerular Complex of the Masu Salmon

Using immunohistochemical labeling of the cells containing neuronal NO synthase (nNOS), tyrosine hydroxylase (TH), GABA, and parvalbumin (PA), as well as histochemical marking of choline acetyltransferase-containing neurons, we examined the neurochemical organization of the glomerular nuclei and preglomerular complex in the brain of the masu salmon (Oncorhynchus masou). Injections of the carbocyanine dye DiI allowed us to examine projections of neurons of the preglomerular and mammillary nuclei in the salmon brain. We showed that cholinergic, GABA-, PA-, TH-, and nNOS-immunopositive neurons belonging to different morphological types are present in the glomerular and medial preglomerular nuclei. The analysis of correlations between morphometric characteristics of the cells belonging to different neurochemical types and densitometric estimates of amounts of neurochemical agents present in these cells allowed us to hypothesize that there are close morphofunctional interrelations in cell populations possessing different neurochemical and morphometric characteristics. These interrelations of the cells belonging to different chemotypes are, probably, realized as mediatory/modulatory ones. The presence of a great number of small slightly differentiated cells in the preglomerular and glomerular nuclei allows us to suppose that the growth of the greatest sensory center of the salmon brain is provided by neuroblasts that migrate from the proliferative zones in the course of postembryonal neurogenesis. It is also hypothesized that NO, TH, and GABA are involved in paracrine control of the postnatal morphogenesis of the salmon preglomerular complex. The data obtained by hodological analysis indicate that the nuclei of the preglomerular complex obtain afferent projections from the dorsomedial and ventroventral telencephalic regions, preoptic nucleus, periventricular layer of the tectum, and posterior central thalamic nucleus. Our study demonstrated the existence of reciprocal functional connections between the preglomerular complex (most important diencephalic center for transmission of sensory information) and dorsomedial and ventral regions of the telencephalon in the masu salmon.     

Morphofunctional interaction of CART peptide and dopaminergic brain neurons

In Wistar rats, after 6 h of sleep deprivation and subsequent 2 h postdeprivation sleep, we found significant changes in optical density of CART peptide in neurons of nucleus accumbens and hypothalamic nucleus arcuatus as well as in processes coming into substantia nigra from nucleus accumbens. The obtained data revealed unidirectional changes of optical density of CART and tyrosine hydroxylase in the studied structures: a decrease after sleep deprivation (p < 0.05) and, on the contrary, an increase after postdeprivation sleep (p < 0.05). Confocal laser microscopy showed morphological connections of CART and dopaminergic neurons and possible colocalization of these both substances in the same neuron at the postdeprivation sleep. In experiments in vitro, after 1 h of incubation of surviving brain sections from the substantia nigra area in the medium with CART peptide there was revealed a rise of optical density of tyrosine hydroxylase in the substantia nigra pars compacta by 55% (p < 0.05). The obtained data indicate an activating effect of CART peptide on brain dopaminergic neurons and its role as a modulator of their functional activity.     

Development of mammalian nervous tissue transplanted into the brain and anterior chamber of the eye: problems and prospects

Some theoretical problems arising in connection with nervous tissue grafting in mammals are discussed. The survival of grafts in the brain and anterior eye chamber is provided by a complex of factors, including peculiarities of immunological reaction, blood-brain barrier and certain characteristics of embryonic nervous tissue. Organotypic development of ectopic grafts suggests a significant autonomy of inner genetic programmes in self-organization of brain structures. Development of the graft-host brain nervous connections is, to a great extent, determined by the factors of topographic closeness and the presence of free postsynaptic structures, without prominent specificity of the graft-brain relationships. Complex neurotrophic interactions, mainly provided by the glial cells, are also found between the graft and damaged host brain. A study of electric activity of the grafted neurons has shown a varying degree of dependence of the functional organization of the brain structures on the environmental afferent influences. The grafts can serve as a chronic endogenous source of neurotransmitters and neurohormones, and, possibly, restore interrupted structural connections, thus providing the compensation of some complex brain functions.