Functional organization of limbic brain structures during conditioned reflex activity in the dog

In experiments on 3 dogs it was shown that instrumental defensive conditioned reflex (CR) to electrical stimulation of the hippocampus is generalized within the limbic system (LS). The rate of generalization depended on the place of testing stimuli in LS. Stimulation of the medial parts of LS at the stage of stabilized initial reflex did not produce the generalized CRs, while they appeared distinctly in response to stimulation of the lateral parts of LS. In the process of elaboration of heterogeneous CRs (defensive and alimentary) to electrical stimulation of the hippocampus, generalized conditioned reactions from some brain structures appeared in both situations to the same degree while from other structures--with considerable differences. These data point to a possible participation in the genesis of the generalized CRs both of signal and reinforcing brain mechanisms.     

The role of signal and motivational links of a conditioned reflex in the initiation of instrumental movements in dogs

Alimentary instrumental conditioned reflex (CR) was elaborated in dogs to light flashes (I series), electrostimulation (ES) of the hippocampus (II series) and the hypothalamus (III series). Nonreinforced ES of the hypothalamus, amygdala, hippocampus and septum reproduced pressings on the pedal to the least extent in the I series (17-40% of trials), increasing in the II-nd one up to 40-87% during stimulation of the lateral hypothalamus, medial amygdala and contralateral hippocampus. In the III-rd series the number of pressings increased statistically significantly in comparison with the I-st series for most structures. Probably, besides the artificial increase of motivation during ES of the limbic structures which took place in all series, in the II-nd and III-rd series significance for movement reproduction was acquired by CR generalization appearing due to close interconnection of the structures. In this phenomenon connections (evaluated by the EPs) from the tested structures to the initially signal one are important.     

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.     

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.     

The role of the basal ganglia in the reproducibility of instrumental reactions acquired to electrostimulation of the hippocampus

In dogs with electrodes implanted into the brain, a defensive instrumental conditioned reflex (CR) was elaborated to light flashes, stimulation of the dorsal hippocampus (DH) and caudate nucleus (CN) stimulation. Reproducibility of the learned movement was tested for the contralateral DN, CN, nucleus accumbens (AN) and pallid globe (PG). In the second series the percent of the elicited movements was compared to EPs, appearing in response to signal and testing stimulation. The degree was elucidated of structures participation in motivational, signal and executive links of CR. Low degree of AN participation in the executive CR link (2-nd series) and a high degree of AN and PG participation in the signal link (3-d series) were shown. Thus, intrasystemic CR generalization was more effective than the intersystemic one.     

A collector of evoked potentials]

The collector is an adaptive algorithm for pattern recognition. It proposes new in-line fully-automatic technique to learn and recognize effective patterns of input data stream. Evoked potentials (EP) were recorded by ADDA 100 KHz, 4 channels, and described by 200 points per each EP. The collector recognized different studies of conditioned response (CR) by patterns of EPs in amygdalar central nucleus. In dogs with implanted into the limbic structures concentric electrodes an instrumental CR was elaborated to electrical stimulation of the dorsal hippocampus. Generalization or transfer of this CR was tested by means of electrostimulation of amygdalar basal nucleus. The generalization in the first experiment took place approximately in 86% of cases, in the second one in 52% of cases. In the first experiment the amplitudes of initial negativity and of late positive waves were smaller than those in the second one and in the experiments before conditioning.     

The role for the hippocampus in the biorhythmical behavior

The hippocampus as a important limbic structure has polyfunction properties among which take place chronotropic activity. It is showed in instability of different biological rhythms that provided for adaptation of organism to changing environment conditions. Chronotropic activity may be depenede from reciprocal connections of the hippocampus with brain rhythmorganizing structures (suprachiasmatic nuclei of hypothalamus and pineal gland). Increase of hippocampal excitability after chronic stress are produce disorganization of some rhythmic processes and followed neurosis or psychical depression. Psychotropic drugs (anxiolytics and antidepressants) by means of intensified of hippocampal inhibitory mechanisms (previously GABA and 5-HT) are stabilized of biorhythms what determined their specific anxiolytic and antidepressant effects.     

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.     

Olfaction in peking ducks (Anas platyrhynchos): A comparative study of centrifugal and centripetal olfactory connections in young ducks and in embryos and ducklings (Aves)

Summary Our study of young white Peking ducks (Anas platyrhynchos) revealed that their main olfactory centres are very similar to those reported for pigeons. Additionally, two major olfactory tracts and other olfactory centres were found to be intimately associated with telencephalic and diencephalic limbic structures. Our results make it possible to reject the view that olfaction in birds is not connected with the limbic system, as is the case in other vertebrates. The occurrence of olfaction was found to be considerably higher in embryos and ducklings. Embryonic connections are more extensive than the olfactory structures of young ducks, covering the archipallial wall of the hemisphere, i.e. the dorsomedial hippocampus and the main laminae of the forebrain. Transitory centripetal olfactory connections develop in embryos, and centrifugal olfactory connections are present in ducklings at the time of hatching. Controls revealed that a portion of the olfactory connections is drastically reduced by physiological degeneration involving connections emanating from both directions. Ultrastructural examination of embryonic archipallial structures revealed that the degeneration is partially the result of the dispersal of innervated neurons. Phylogenetically, one may compare the significant involvement of transitory olfactory connections in the anlage of limbic structures with the conditions occurring in anamniot vertebrates. This supports the hypothesis that the primary development of transitory olfactory connections represents an ontogenetic recapitulation of ancestral conditions, by which the structural and functional organization of the avian brain is influenced.     

Effect of repeated daily electrical stimulation on seizure activity in the rabbit limbic system

The order of appearance, the functional relations, and changes in the epileptiform effects of electrical stimulation of the limbic system (septum, amygdala, hippocampus) were studied. During repeated electrical stimulation regular changes took place in the seizure activity: the duration, frequency, and amplitude of the after-discharges were increased, their polarity was changed, seizures and unsynchronized high-amplitude activity appeared, and the after-discharges were reactivated. The most common variants of the seizure patterns are described. Close correlation was found between the greatest intensity of the after-discharges and the appearance of seizures. Besides a critical number of after-discharges, their parameters and their degree of irradiation also play an important role in the onset of the seizures. It is postulated that the limbic structures may play the role of an organized epileptogenic focus. Facts indicating that the seizure activity in response to direct electrical stimulation of the limbic structures may have a reflex mechanism are presented.     

Adrenocortical Steroids Modify Neurotransmitter-Stimulated Cyclic AMP Accumulation in the Hippocampus and Limbic Brain of the Rat

Glucocorticoid hormones are known to affect limbic system structures that have high levels of specific receptors for glucocorticoids, especially the hippocampus (HIPP). To understand how glucocorticoids may affect synaptic transmission, we have tested the effects of adrenal removal and glucocorticoid replacement on neurotransmitter-stimulated cyclic AMP accumulation in brain slices from the rat limbic system. Adrenalectomy (ADX) caused an enhancement of vasoactive intestinal peptide (VIP)-stimulated cyclic AMP accumulation in HIPP, amygdala (AMYG), and septum (SEP). In HIPP, ADX increased the cyclic AMP response to isoproterenol (ISOP) and decreased the response to histamine (HIST). In the AMYG and SEP, ADX did not affect significantly the action of ISOP, but ADX did decrease the response to HIST in AMYG. Administration of dexamethasone or corticosterone reversed the effects of ADX on cyclic AMP accumulation in the HIPP. The dexamethasone action on VIP-stimulated cyclic AMP accumulation takes place within 48 h and is most apparent in the mid-range of the VIP dose-response curve. These results demonstrate that glucocorticoids regulate neurotransmitter-stimulated cyclic AMP generation in a fashion that is specific, both for the neurotransmitter involved and for the brain regions affected.     

Ginsenoside RG1 and corticosteroid receptors in rat brain

Old (28 months) male Wistar rats were treated chronically for two weeks with ginsenoside Rg1 or with vehicle delivered via sc implanted Alzet mini-pumps (rate of ginsenoside release 2.4 micrograms/0.5 microliter/h). The number of Type 1 corticosterone-preferring receptor sites (CR) and Type 2 glucocorticoid receptors (GR) was measured in the cytosol of hippocampus tissue of rat brain with an in vitro binding assay. In old rats the Bmax of Type 1 CR and Type 2 GR was reduced by 51.5% and 28.3% respectively. Following the two week treatment with Rg1 the Bmax of Type 1 CR increased by 60% and a receptor concentration was reached which was 21% lower than that observed in the young control animals. Minor differences in affinity of steroid binding to both receptor systems were observed in the groups of rats. The possible binding of ginsenosides to brain corticosteroid receptors in vitro was investigated as well. The inclusion of a 500 fold molar excess of Rg1 in hippocampus cytosol did not displace 3H-corticosterone from its soluble receptor sites. The affinity of Rg1 with these sites in vitro is therefore negligible. In conclusion, the binding capacity of Type 1 CR and Type 2 GR is reduced in the hippocampal brain region of aged rats. Upon chronic infusion of ginsenoside Rg1, only Type 1 CR capacity is restored towards the level observed in young control animals. This finding suggests that in old rats the ginsenoside enhances the CORT signal via Type 1 CR on the function of the hippocampus, which is a limbic brain structure involved in cognition, mood and affect.     

Dopamine-dependent interactions between limbic and prefrontal cortical plasticity in the nucleus accumbens: disruption by cocaine sensitization

The prefrontal cortex and the hippocampus exhibit converging projections to the nucleus accumbens and have functional reciprocal connections via indirect pathways. As a result, information processing between these structures is likely to be bidirectional. Using evoked potential measures, we examined the interactions of these inputs on synaptic plasticity within the accumbens. Our results show that the direction of information flow between the prefrontal cortex and limbic structures determines the synaptic plasticity that these inputs exhibit within the accumbens. Moreover, this synaptic plasticity at hippocampal and prefrontal inputs selectively involves dopamine D1 and D2 activation or inactivation, respectively. Repeated cocaine administration disrupted this synaptic plasticity at hippocampal and prefrontal cortical inputs and goal-directed behavior in the spatial maze task. Thus, interactions of limbic-prefrontal cortical synaptic plasticity and its dysfunction within the accumbens could underlie complex information processing deficits observed in individuals following psychostimulant administration.     

Total RNA content and blood flow in rat brain after RNA administration

The changes in blood flow through selected brain structures and the changes in the total RNA content of cells of these structures were examined after a single administration of yeast RNA to 6-month-old male rats. The total content of ribosomal RNA in cells of the limbic system (septum, hippocampus, hypothalamus) increased 48 hrs after the administration of 100 mg i.p. yeast RNA , dropped after 7 days (in hypothalamus), 21 and 30 days (in hippocampus), 30 days (in septum). In cells of the limbic system as a whole there is a higher total RNA content in experimental rats. No changes were observed in the cells of parietal brain cortex. Blood flow increased in limbic structures 21 and 30 days after RNA administration and in septum and in hippocampus also 90 days after application. No changes were observed in parietal brain cortex, bulbi olfactorii, cerebellum and brain stem. Histochemical changes correlated positively with blood flow changes in the limbic system 14, 21, 30 and 90 days after RNA application. The body weight of experimental rats did not differ from that of control animals. The changes in haemodynamic parameters were transient and were demonstrated as fluctuations in heart rate, cardiac output, and peripheral resistance. Blood pressure experienced no changes.     

Different neurophysiological mechanisms underlying delayed reaction and trace conditioned reflex

Electrophysiological study of functional interactions of the prefrontal cortex, the hippocampus, the head of the caudate nucleus and the thalamic medio-dorsal nucleus in 2 monkeys in conditions of the trace reflex and delayed reaction has revealed various morphofunctional systems for these types of memory. The morphofunctional system of the trace CR is characterized by greater stability and a small number of functional connections (21%) in contrast to the dynamic morphofunctional system with a considerable percentage of functional contacts (54%) in case of the delayed reaction. This difference can be very likely related to the different dynamics of functional connections between brain structures rather than to the involvement of various brain structures.     

Electroencephalographic correlates of a pathologic inert motor reaction in dogs]

Changes in EEG were examined during setting in of a pathological inert motor reaction in dogs with parts of the tongue brought out and electrodes implanted in the motor cortical area and limbic structures. The reaction was formed when combining stimulation by a salt solution of the part of the tongue with electrical stimulation of the paw. The inert motor reaction is characterized by enhanced synchronization (theta-rhythm) in the hippocampus and increased amplitude of the beta-rhythm in the motor cortical areas. A frequency-amplitude analysis of the summary EEG has shown that the highest correlation was established at the beginning of elaboration of the inert motor reaction only between a small number of limbic structures (the hippocampus, the hypothalamus and the cingulate gyrus), then between all the examined structures of the brain; when the inert reaction became elaborated the number of structures with a high correlation coefficient diminished again and was reduced to the hippocampus, the hypothalamus and the cortical motor area.     

Distribution and daily fluctuation of the available glucocorticoid binding sites in different areas of the quail brain

The distribution and daily fluctuation of available glucocorticoid binding sites was studied in the brain of the quail Coturnix coturnix japonica, under physiological circumstances. A high level of triamcinolone acetonide binding was observed in some limbic structures (hippocampus and archistriatum), in the nucleus medialis and lateralis posterioris hypothalami and in the cerebellar cortex. The daily fluctuation of the available glucocorticoid binding sites in the preoptic area, hippocampus, archistriatum and cerebellar cortex can be described with a curve antiphased to the daily rhythm of plasma corticosterone concentration and seems to be synchronized by the plasma corticosterone level.     

Various neurochemical aspects of the action of the tetrapeptide tuftsin on limbic system structures (histochemical and biochemical study)

Tetrapeptide tuftsin action on the activity of succinate dehydrogenase (SDG), malate dehydrogenase (MDG) and monoamine-oxidase (MAO) in microstructures of the neocortex, hippocampus and hypothalamus (supraoptic and paraventricular nuclei, retrochiasmic zone) has been investigated by means of histochemical methods. Simultaneously, pyruvate-, malate-, glutamate-, alfaketoglutamate-, succinate- and lactate-dehydrogenase activity in the neocortex and in the structures of the limbic system has been studied biochemically. SDG and MDG activity increases in neurons and glycocytes of all the hypothalamic formations mentioned. Changes in the activity of dehydrogenases in the hippocampus and neocortex under the same stimulation are less pronounced. MAO activity also increases in the nerve terminals converging on the bodies and dendrites of hypothalamic neurons and in the preterminal fibers of the neocortex, Tuftsin increases oxidative-reducing processes in various structures of the brain, but at the same time it possesses a predominant influence on the limbic system structures.     

Retrosplenial and hippocampal projections of structures of the thalamoparietal associative system in rats

Afferent connections of the nucleus lateralis posterior (NLP) of the thalamus and area 7 of the parietal cortex with the retrosplenial region of the limbic cortex and hippocampus were studied in rats with retrograde axon transport of horseradish peroxidase. It was shown that the NLP receives ipsilateral projections from area 29d neurons, while area 7 receives ipsilateral axons from area 29d and 29c neurons. It was found that associations of the retrosplenial region with associative cortex are far more pronounced than with associative thalamus. Moreover, the afferent connections of area 7 with area 29d are more numerous than with area 29c. We disclosed no projections of areas 29a and 29b to thalamoparietal system structures. In addition to neocortical input from the limbic cortex, area 7 receives afferent fibers from the archicortex; neurons situated in hippocampus area CA1 are the source of these projections.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy Academy of Sciences, Leningrad. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 647–655, November–December, 1991.     

Alterations of spectral parameters of rat brain electrical activity after sciatic nerve section

Changes in electrophysiological brain characteristics accompanying the development of neurogenic pain syndrome induced by transsection of sciatic nerve were analyzed. At the maximum pain syndrome 3 weeks after the deafferentation, a reorganization of the brain electrical activity was observed in the limbic structures (hippocampus, amygdale, and nucleus accumbens), frontal cortex, and the caudate putamen. An increase in the relative spectral power of the delta and alpha bands and a decrease in the relative power of the beta2 band (as compared to baseline activity) took place. Alteration of the electrical activity in the limbic structures did not depend on manifestations of the neurogenic pain syndrome (autotomy). The increase in the relative spectral power of the alpha-band activity in all the structures under study suggests the involvement of the reticular thalamic nucleus in pathogenesis of neurogenic pain syndrome.