Differences in activity of hippocampal and neocortical neurons in active and passive rabbits in negative emotional situations

Activities of individual hippocampal (CA1 area) and neocortical parietal-temporal neurons were compared in active and passive rabbits in negative emotional situations during emotionally significant stimuli by plotting histograms of autocorrelations. As compared to passive animals, in active rabbits, the mean firing rate of hippocampal neurons was higher, bursting and periodic oscillations of discharges occurred more frequently. Oscillation periods in the theta 1 band (6.0-9.0 Hz) appeared more frequently (in the baseline state and active exploratory or defensive reactions), whereas those in the theta 2 band (4.0-5.9 Nz), on the contrary, were infrequently observed (during freezing). The greatest changes in activity ofhippocampal neurons were observed during active locomotor responses of active rabbits. Intergroup differences in neocortical neuronal activities were less pronounced than in hippocampus. The results indicate that individual typological features in behaviour of animals appear in negative emotional situations and are reflected in activity of activity ofhippocampal (area CA1) and to lesser extent parietal-temporal neocortical neurons. The results suggest different activation levels of the septohippocampal system of active and passive rabbits and possible differences in the afferent input to the CA1 field.     

Interhemisphere asymmetry of hippocampus and neocortex in correlates of active and passive behavioural strategy in negative emotional situations

The interhemisphere interaction of neurons in bilateral derivations from parietal and sensomotor areas of neocortex and the area CA1 of hippocampus were studied in rabbits with active and passive behavioural strategy in the open field by plotting histograms of crosscorrelation. In passive animals, there was asymmetry in bilateral neuronal interaction: with right-sided dominance in the neocortex and with left-sided that--in the hippocampus. On the contrary, in active rabbits, the left-sided dominance was observed in the neocortex, and the lateralization was not revealed in the hippocampus. The brain laterality was reflected in motor asymmetry of animals in preferring left or right turns in the open field. Passive rabbits made relatively more left turns, and the active animals--right turns. Systemic administration of agonist GABA(B) receptors phenibut decreased behavioural responses to emotional stimuli and eliminated interhemisphere asymmetry observed usually in negative emotional situations. Thus the interhemisphere asymmetry of the neocortex and hippocampus is correlated with individual typological characteristics of animals and reflects the readiness to preferential forms of behavioural responses in active and passive rabbits.     

Effects of intra-amygdala injection of GABA(A)-receptor agonist and antagonist on behavior of active and passive rabbits in negative emotional situations

The effects of right-side or left-side intra-amygdala injections of the GABA(A)-receptor agonist muscimol hydrobromide (0.1 microg/1 microl) and antagonist bicuculline methiodide (0.05, 0.1, 0.5 microg/1 microl) on the behavior of active and passive rabbits were studied in open field, light-dark test and during presentation of emotionally significant stimuli. The effect of compounds injection was differed in active and passive rabbits. The active rabbits were more sensitive to bicuculline injection and the passive rabbits to muscimol administration. Bicuculline induced anxiolytic-like effects on the active animals in open field, light-dark test and motor-activating effects during emotionally significant stimuli. Muscimol induced anxiolytic-like effects on the passive rabbits and sedative effects on the both groups of rabbits. The differences in effectiveness of right-side and left-side intra-amygdala injections on behavior of rabbits were revealed: more powerful changes were during injection of bicuculline in left and muscimol in right amygdala. Anxiolytic-like effects were revealed during injection of bicuculline into left amygdala of active rabbits and muscimol into right amygdala of passive rabbits. These findings indicate that there are individual-typological and interhemispheric differences in functioning of GABAergic system of amygdala.     

Influence of anxiolytic afobazole on amygdalar neuronal activity and behavior of rabbits in emotionally negative situations

The influence of systemic injection of anxiolytic afobazole (1 mg/kg) on interaction between neurons of the basal and central amygdaloor nuclei and behavior of rabbits in negative emotional situations was studied in order to reveal characteristics of amygdalar neuronal network properties during unconditioned fear. An afobazole injection results in a prolongation of stay in the light compartment of dark-light chamber, in a decrease in freezing probability after exposure of emotional stimuli, in appearance of some aggressive reactions in open field. Behavioral alterations were accompanied by duration increase and latency changes of amygdalar neuronal inhibitory interactions, by increase of probability of neuronal interactions on delta-range frequency, by decrease of interactions on theta-range frequency. Under the influence of afobazole the asymmetry with right dominance in interhemispheric interaction of amygdalar neurons decreased. Changes in network properties ofamygdalar neurons during afobazole injection testify to reduction of activation level of this structure taking place at the expense of enhancement of inhibitory interactions between neurons.     

Microelectrophoretic investigation of cholinoceptive amygdalar neurons

Responses of spontaneously active amygdalar neurons to acetylcholine, atropine, and sodium L-glutamate, administered by microelectrophoresis, were investigated in acute experiments on unanesthetized cats. The most characteristic response to acetylcholine was an increase in firing rate (37.9% of cells). Activity of 8.6% of neurons was inhibited. Mainly cholinoceptive neurons responded to atropine. Responses of the same neuron to acetylcholine and atropine, applied consecutively through the microelectrode, were in every case of opposite sign. The latent periods of the responses to acetylcholine and atropine and the duration of the after-effect were longer than for responses to sodium L-glutamate.Institute of Physiology, Siberian Division, Academy of Sciences of the USSR, Novosibirsk. Translated from Neirofiziologiya, Vol. 4, No. 6, pp. 645–650, November–December, 1972.     

Changes in neurochemical properties of mesencephalic reticular neurons during negative emotional reactions

On microiontophoretic application of acetylcholine, noradrenalin, and serotonin to single neurons of the mesencephalic reticular formation of unanesthetized rabbits, qualitative changes in responses to one or more of these biologically active substances were discovered in about 50% of cells after electrical stimulation of the negative emotiogenic zone of the ventromedial hypothalamus. Changes in chemical sensitivity of reticular neurons to noradrenalin and serotonin were observed twice as often as to acetylcholine. It is suggested that a reorganization of the neurochemical properties of the central neurons may be one of the mechanisms of formation of negative emotional states.P. K. Anokhin Research Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 5, pp. 506–514, September–October, 1981.     

Network activity of "interneurons" and large cells of amygdala in active and passive rabbits

By plotting cross-correlation histograms differences were found in interaction of conjectural small "interneurons" and large principal cells of the central and basal amygdalar nuclei in negative emotional situations. The network activity of "nterneurons" was higher than in principal cells. "Interneurons" more frequently had excitatory and inhibitory input or output connections with neighbouring cells, latency of their connections with other cells was smaller than in principal neurons. Interaction of "interneurons" and principal cells differed in animals with active and passive behavioural strategy in negative emotional situations. As compared to active animals, in passive rabbits inhibitory connections to "interneurons" from other cells occurred more frequently, excitatory or inhibitory connections from "interneurons" to principal cells appeared more rare.     

Effect of GABA receptor agonist phenibut on behavior and respiration of rabbits in the negative emotional situation

The influence of systemic injection of GABA-receptor agonist--phenibut (40 mg/kg, s/c) on open field behavior, behavioral reactivity and changes in respiratory parameters after exposure of negative emotional stimuli was studied in three rabbit groups differentiated by locomotor activity in open field (active, passive and medium-active animals). The injection of phenibut results in decrease of rabbits horizontal locomotor activity and some components of research behavior in open field and also decrease of behavioral reactivity on emotional stimuli. At the same time the probability of both an active orienting exploratory or defensive reactions and passive reactions (freezing) were decreased. The influence of phenibut depended on typological features of rabbits: the most potent effect occurred upon behavior of active rabbits, less on passive animals and practically none on medium-active rabbits. The phenibut injection results in increase of duration of inhalation during exposure to emotional stimuli, whereas it decreased in normal.     

Effects of neurotensin on active and passive avoidance performance in rats with lesions of serotoninergic neurons

After a lesion of serotoninergic neurons performed by administration of 5.7-dihydroxytriptamine into the dorsal raphe nucleus, effects of neurotensin microinjections into the substantia nigra on rat behavior were investigated. Serotoninergic lesions resulted in enhanced fear of rats manifested as an increase in the number of intersignal avoidance reactions and intensification of escape reactions. Neurotensin microinjections into the substantia nigra diminished the neurotoxin action thus increasing the adaptive character of defensive behavior of rats with deficit of functions of serotonin neurons.     

Impulsation of hypothalamic and amygdalar neurons in bilateral derivations in the state of food motivation

The character of impulsation of single neurons in the lateral hypothalamic and amygdalar central nucleus of rabbits recorded in bilateral derivations during quiet wakefulness, after 24-h food deprivation, and after satiation was studied by plotting autocorrelation histograms and by counting the mean frequency of discharges. During the transition from hunger to satiation, the character of impulsation of neurons in hypothalamus and amygdala changed in different ways: (1) a greater number of hypothalamic than amygdalar neurons changed their mean discharge frequency (85 versus 56%, respectively); (2) in hunger, the number of hypothalamic neurons with delta-frequency oscillations decreased as compared to quiet wakefulness and satiation, and in the amyglala the number of neurons with beta2-frequency oscillations increased; (3) in hunger, the number of hypothalamic neurons with bursting and periodic discharges decreased and the number of amygdalar neurons with equiprobabilistic discharges increased. During state alternation (according to the autocorrelation histograms) the strongest changes in the character of neuronal discharges took place in the left hypothalamus and left amygdala. The maximum differences in neuronal impulsation between the left and right hypothalamus were observed in the state of hunger and between the left and right amygdala, after satiation.     

Interaction of aminoacyl-tRNA synthetases and tRNA: Positive and negative cooperativity of their active centres

The influence of tRNA on the kinetics of PP-ATP exchange and aminoacyl-tRNA formation catalysed by leucyl-, phenylalanyl-, and tryptophanyl-tRNA synthetases has been investigated. These enzymes were chosen because they belong to three main classes of quaternary structure ₁, ₂₂ and ₂, respectively. The present paper shows that the investigated synthetases manifest kinetic cooperativity of the active centres which is negative in the case of AAA formation and positive in the case of leucyl- and tryptophanyl-tRNA synthesis. The obtained data were interpreted with the aid of the trigger model of the enzyme.     

Interaction of neuropeptide Y and corticotropin-releasing factor signaling pathways in AR-5 amygdalar cells

Corticotropin-releasing factor (CRF) is a 41 amino acid neuropeptide which is involved in the stress response. CRF and neuropeptide Y (NPY) produce reciprocal effects on anxiety in the central nucleus of the amygdala. The molecular mechanisms of possible CRF-NPY interactions in regulating anxiety behavior is not known. In the central nervous system, the action of NPY leads to inhibition of cAMP production while CRF is known to stimulate levels of cAMP in the brain. Consequently, we hypothesized that NPY may antagonize anxiety-like behavior by counter-regulating CRF-stimulated cAMP accumulation and activation of the protein kinase A pathway. We have engineered an immortalized amygdalar cell line (AR-5 cells) which express via RT-PCR, the CRF₂, Y₁ and Y₅ NPY receptor. In addition, in these cells CRF treatment results in significant concentration-dependent increases in cAMP production. Furthermore, incubation of 3 μM CRF with increasing concentrations of NPY was able to significantly inhibit the increases in cAMP compared to that observed with 3 μM CRF treatment alone. These findings suggest that CRF and NPY may counter-regulate each other in amygdalar neurons via reciprocal effects on the protein kinase A pathway.     

Individual propensity to active or passive behavior during exposure to emotional stress in individuals with various blood cortisol levels

Effects of baseline and reactive blood cortisol on operator's performance were studied in subjects with active of passive behavioral reactions under exposure to stress. The type of behavioral reaction to stress (shift in the rates of omissions or false alarms) was found to be associated with the baseline blood cortisol and its levels averaged in the course of the experiment. Subjects with active reaction (stress produces an increase in the rate of errors of the false-alarm type) were characterized by the low cortisol level, whereas its high level was observed in subjects with passive reaction (stress produces an increase in the rate of errors of the omission type). Individuals with high baseline cortisol level and those with the passive reaction to stress exhibited enhanced cardiovascular reactivity during performance in normal conditions and its reduction during the performance under exposure to stress.     

Structure-preserving model reduction of passive and quasi-active neurons

The spatial component of input signals often carries information crucial to a neuron’s function, but models mapping synaptic inputs to the transmembrane potential can be computationally expensive. Existing reduced models of the neuron either merge compartments, thereby sacrificing the spatial specificity of inputs, or apply model reduction techniques that sacrifice the underlying electrophysiology of the model. We use Krylov subspace projection methods to construct reduced models of passive and quasi-active neurons that preserve both the spatial specificity of inputs and the electrophysiological interpretation as an RC and RLC circuit, respectively. Each reduced model accurately computes the potential at the spike initiation zone (SIZ) given a much smaller dimension and simulation time, as we show numerically and theoretically. The structure is preserved through the similarity in the circuit representations, for which we provide circuit diagrams and mathematical expressions for the circuit elements. Furthermore, the transformation from the full to the reduced system is straightforward and depends on intrinsic properties of the dendrite. As each reduced model is accurate and has a clear electrophysiological interpretation, the reduced models can be used not only to simulate morphologically accurate neurons but also to examine computations performed in dendrites.     

Dendritic morphology of hippocampal and amygdalar neurons in adolescent mice is resilient to genetic differences in stress reactivity

Many studies have shown that chronic stress or corticosterone over-exposure in rodents leads to extensive dendritic remodeling, particularly of principal neurons in the CA3 hippocampal area and the basolateral amygdala. We here investigated to what extent genetic predisposition of mice to high versus low stress reactivity, achieved through selective breeding of CD-1 mice, is also associated with structural plasticity in Golgi-stained neurons. Earlier, it was shown that the highly stress reactive (HR) compared to the intermediate (IR) and low (LR) stress reactive mice line presents a phenotype, with respect to neuroendocrine parameters, sleep architecture, emotional behavior and cognition, that recapitulates some of the features observed in patients suffering from major depression. In late adolescent males of the HR, IR, and LR mouse lines, we observed no significant differences in total dendritic length, number of branch points and branch tips, summated tip order, number of primary dendrites or dendritic complexity of either CA3 pyramidal neurons (apical as well as basal dendrites) or principal neurons in the basolateral amygdala. Apical dendrites of CA1 pyramidal neurons were also unaffected by the differences in stress reactivity of the animals; marginally higher length and complexity of the basal dendrites were found in LR compared to IR but not HR mice. In the same CA1 pyramidal neurons, spine density of distal apical tertiary dendrites was significantly higher in LR compared to IR or HR animals. We tentatively conclude that the dendritic complexity of principal hippocampal and amygdala neurons is remarkably stable in the light of a genetic predisposition to high versus low stress reactivity, while spine density seems more plastic. The latter possibly contributes to the behavioral phenotype of LR versus HR animals.