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.     

Field potentials evoked in the subiculum following postsynaptic discharge of hippocampal pyramidal neurons

Evoked potentials, represented by population spikes and slow waves, have been recorded from the subiculum, along its whole dorso-ventral extent, following postsynaptic activation and discharge of hippocampal pyramidal neurons. These potentials can be associated with synaptic excitatory effects generated on radially oriented neurons by hippocampal impulses reaching the subiculum at any dorso-ventral level, according to a segmental organization.     

Activity of rabbit's neocortical and hippocampal neurons in orienting-exploratory behavior and freezing

By plotting autocorrelation histograms, the character of impulsation of neurons in bilateral derivations from cortical visual and somatosensory areas and hippocampal field CA1 was studied in rabbits during free behavior under the influences of emotional stimuli. During active orienting-exploratory reaction of rabbits, most cortical and hippocampal neurons manifested bursting discharges and theta-frequency oscillation (predominantly 4-5 Hz in cortex and 4-5, 6-7 in hyppocampus). During freezing, as compared with active locomotor reaction, the number of neurons with equiprobabilistic discharges increased; in impulsation of neurons with periodicity, the intensity of delta-frequency oscillation increased (predominantly 2-4 Hz) but theta-frequency oscillation decreased. The number of neurons with delta-frequency oscillation during freezing was greater then in calmly sitting rabbits.     

Effect of electrical stimulation of the hippocampus and neocortex on cingulate cortical neurons in rabbits

Extracellular unit activity of the anterior and posterior zones of the cingulate cortex and also of the anterior and posterior cortical association areas was analyzed in unanesthetized rabbits. In the posterior zone considerably more cells (60%) responded to hippocampal stimulation than in the anterior zone (18%). In 43% of these cells in the posterior zone but only in 5% in the anterior zone, the responses followed the frequency of stimulation. Unit responses in the posterior zone could be divided into two discrete groups: those with short (12.3 ± 6.5 msec) and those with long (50.2 ± 10.0 msec) latent periods. Inhibitory phenomena also were well marked during hippocampal stimulation. More than one-third of cells of the cingulate cortex responded to stimulation of the posterior association zones by spikes which followed the stimulus, and by subsequent inhibition. Responses of this kind to stimulation of the anterior association zones were found in only a few cells in the anterior zone of the cingulate cortex. The results are discussed in the light of data from morphological investigations relating to connections between these structures.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 270–277, May–June, 1982.     

Effect of cortisol microiontophoresis on discharge time structure of dorsal hippocampal neurons in rabbits

The effect of microiontophoretic application of cortisol to single neurons of the dorsal hippocampus on the character of distribution of interspike intervals in their discharges was studied in chronic experiments on rabbits. Cortisol modified the time structure of regular and rhythmic discharges of hippocampal neurons. Regularization of discharges in the form of bursting activity appeared as the result of cortisol in cells with irregular spontaneous activity. Activity of more than half of the neurons, in which bursting discharges corresponded in frequency to the theta-rhythm, was intensified as a result of microapplication of cortisol. In neurons discharging complex spikes, in which under normal conditions a phenomenon of reduction of spike amplitude was observed within each burst, no definite rule as regards changes in the time structure of the discharges could be observed after administration of the hormone. It is suggested that cortisol plays a modulating role in mechanisms of generation of spike activity by hippocampal neurons.P. K. Anokhin Research Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 6, pp. 628–635, November–December, 1981.     

Spontaneous activity of hippocampal neurons and stimulation rhythm acquisition in young rabbits during learning: age features

Ontogenetic mechanisms of memory formation were studied using an experimental model of conditioned reflex to time, i.e., trace acquisition of a stimulation rhythm by hippocampal CA1 neurons of young (1-4 weeks old) and adult rabbits (5-6 months old). It was found that age-related development of learning ability includes several stages: complete absence of memory traces (6-7 days old), rapid acquisition without consolidation (8-14 days old), and formation of perfect memory (25-30 days old). Both specific and nonspecific changes in spontaneous activity of neurons were observed. Changes in the rate of discharges related to rhythmic stimulation were accompanied by changes in spontaneous activity. With the development of an animal, spike activity increased in parallel with improving of the functional properties of neurons, their structural organization, formation of the afferent contacts in the hippocampus completed after a period of three weeks from birth, and formation of metabolic processes, modulatory systems, and traffic function of hippocampal neurons. A capability for plastic reorganization is of great importance for adaptation mechanisms and conditioned behavior of a developing animal in accordance with structural maturation and development of the functional regulation of neuronal reactivity in the hippocampus.     

Inhibition in hippocampal pyramidal neurons during peripheral stimulation

Responses of hippocampal pyramidal neurons were investigated intracellularly in unanesthetized rabbits immobilized with tubocurarine. A single stimulus, applied to the sciatic nerve, evoked prolonged (up to 2.5 sec) hyperpolarization of the cell membrane, accompanied by inhibition of action potentials. The latent period of the evoked hyperpolarization was 48±16.4 msec, and its amplitude 2.5±1.9 mV. In some neurons the development of hyperpolarization potentials was preceded by excitation. The suggestion is made that hyperpolarization of the membrane of pyramidal cells during peripheral stimulation is manifested as an inhibitory postsynaptic potential (IPSP), generated with the participation of hippocampal interneurons. The possibility of prolonged tonic action of interneurons from outside as a cause of prolonged inhibition of the pyramidal neurons is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 3, pp. 278–284, November–December, 1969.     

Guanine nucleotides inhibit NMDA and kainate-induced neurotoxicity in cultured rat hippocampal and neocortical neurons

Previous evidence suggests that guanine nucleotides can directly inhibit N-methyl-d-aspartate (NMDA) and AMPA/kainate receptors and antagonize a variety of cellular functions elicited by these glutamate receptor agonists. We investigated the possibility that the guanine nucleotides GTP, GDP, and GMP exert a neuroprotective effect on cultured rat hippocampal or neocortical neurons exposed to the excitotoxicants NMDA (30 microM) or kainate (300 microM). On co-application with NMDA all three nucleotides revealed a comparable rescue effect from 100 microM nucleotide concentrations onwards, with a higher inhibitory potential in hippocampal than in neocortical cultures. Similarly, kainate-induced neurotoxicity was inhibited by all three nucleotides but the inhibitory potential was lower than after application of NMDA. Guanosine had no effect on either culture system. GTP and GDP where hydrolyzed by hippocampal and cortical cultures with GMP accumulating in the medium, suggesting that hydrolysis of GTP had no effect on the effective nucleotide concentration. Our results show that GTP, GDP, and GMP inhibit NMDA- and kainate-mediated neurotoxicity in cultured hippocampal and neocortical neurons. They suggest that guanine nucleotides may be candidates for broadly antagonizing glutamate receptor-mediated neurotoxicity.     

The morphochemical characteristics and plastic restructurings of the hippocampal neurons after rhythmic stimulation of an extremity in old rabbits]

The rhythmic activity of CA1 hippocampal neurons was studied after the rhythmic (1-2 Hz) electrocutaneous forelimb stimulation (10-20 min) of 6-84-months-old rabbits. The spectral analysis of neuronal activity revealed the age-dependent decrease in ability to reproduce the rhythm of stimulation. The cytochemical data showed that the protein synthesis in the neurons under study also declined with age.     

Effect of peripheral stimulation on neocortical electrical activity in the chronic premesencephalic cat

Chronic experiments on 19 adult cats showed that on the second or third day after premesencephalic section through the brain stem preserving the lemniscal pathways, auditory, olfactory, and cutaneous stimulation evoke diffuse neocortical activation. Although photic stimulation evoked responses in the visual cortex, it could not desynchronize the neocortical activity. It is postulated that diffuse neocortical activation in cats with a complete block of the mesencephalic recticular formation in response to auditory, olfactory, and cutaneous stimulation arises through excitation of the posterior hypothalamus.Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 7, No. 5, pp. 493–499, September–October, 1975.     

Effect of kyotorphin on the reactivity of hippocampal neurons

The effects of kyotorphin (Tyr-Arg) on CA1 and CA3 field responses were studied on rat hippocampal slice preparations. Slice perfusion with 10(-6)-10(-4) M of kyotorphin resulted in reactivity changes both in mossy fibers (CA3) and Schaffer collaterals (CA1). The principal effect was the increase in pop-spike amplitude. Kyotrophin (10(-6)-10(-5) M) and metenkephalin (10(-7)-10(-6) M) were found to produce similar reactivity changes (facilitation) in CA1 region of most preparations. However, kyotorphin effect, in contrast to enkephalin-induced facilitation was not blocked by naloxone. The data suggest that the mechanisms of kyotorphin action in the hippocamp are not related to endogenous enkephalin release.     

Effect of electrical stimulation of the septum on subicular neurons with different kinds of spontaneous activity in rabbits

The effect of electrical stimulation of the medial nucleus of the septum and of hippocampal area CA₁ on subicular neurons with three different types of spontaneous activity (with theta-modulation, with delta-modulation and complex spikes, and with irregular single-spike activity) was studied in unanesthetized rabbits by extracellular recording of unit activity. Cells with theta-activity were found to respond in a distinctive functional manner to stimulation of the medial nucleus of the septum: Their reactivity was higher but latent periods of their responses were much shorter than those of cells with delta-activity and irregular discharges. Stability of modulation of theta-cell activity increased both during and after stimulation of the medial septal nucleus. Electrical stimulation of hippocampal area CA₁, on the other hand, led to disappearance of rhythm modulation. Average response latencies of all three types of cells to stimulation of area CA₁ were equal. The results indicate special properties of the septal input to subicular cells with theta-modulation.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 17, No. 3, pp. 326–333, May–June, 1985.     

Effect of thrombin on survival of hippocampal neurons

The effect of thrombin on the rat hippocampal neurons death in model of neurotoxicity induced by hemoglobin or glutamate, was studied. Thrombin (10 nM) was shown to inhibit 100-mkM glutamate--or 10-mkM hemoglobin-induced apoptosis of the rat hippocampal neurons. With the aid of PAR1 (protease-activated receptor1) agonist peptide and PAR1 antagonist, the PAR1 was found to be necessary for protective action of thrombin in hippocampal neurons in models of neurotoxicity induced by hemoglobin or glutamate. Because the prolonged elevation [Ca2+] ib neurons is a critical part of neurodestructive processes in CNS, the effect of thrombin on Ca2+-homeostatis of neurons after its injury by the inducer of neuronal apoptosis: a synthetic agonist of the NMDA receptors N-methyl-D-aspartate (NMDA), was studied. We hypothesized that thrombin via receptors PAR may prove to be neuroprotective for the hippocampus. Thrombin was shown to stimulate via PAR1 a transient increase in [Ca2+] in neurons in a concentration-dependent manner. Thrombin (1 nM) decreased the [Ca2+] signal induced by activation of the NMDA-subtype of glutamate receptors. This thrombin effect may be one of the reasons of the protective action of thrombin in hippocampal neurons.     

Effect of NMDA-receptor ligands on neocortical and hippocampal EEG activity of rat brain.

Neocortex and hippocampus play important role in motor activity, neuronal plasticity and learning and memory mechanisms. Electroencephalographic (EEG) activity of neocortex and hippocampus of rat following NMDA-receptor agonist, N-methyl-D-aspartate (NMDA), 0.25-2 nmol in 10 microliters, ICV and noncompetitive NMDA-receptor antagonists, MK 801 (0.025-0.1 mg/kg, ip) and ketamine (10-50 mg/kg, ip) at OH, 1/2H, 4H, 8H and 24H was recorded. The electrodes were implanted stereotaxically in hippocampus and neocortex respectively. NMDA (0.25 and 1 nmol) showed longer lasting decrease in amplitude in hippocampus and in frequency in cortical neurons while 2 nmol produced epileptogenic neurotoxicity. Opposite effect i.e. increase in amplitude in both, hippocampus and neocortex was observed with MK 801 and ketamine and these agents also showed longer lasting influence. Administration of MK 801 (0.05 mg/kg) and ketamine (50 mg/kg) prior to NMDA 2 nmol protected 40% animals from NMDA-induced neurotoxicity and blockade of NMDA-induced long term influence. The EEG effect of NMDA agonist and NMDA-induced neurotoxicity at higher dose and its modification by NMDA-antagonist, MK 801 and ketamine suggest that beside NMDA agonists (NMDA), its antagonists may, also affect long lasting changes in hippocampus and cortex. These antagonists reverse NMDA-mediated long term influence in these brain areas.     

Extra-hippocampal projections of CCK neurons of the hippocampus and subiculum

A population of neurons in the hippocampus and subiculum contains cholecystokinin (CCK). Following transection of the dorsal fornix, a major afferent pathway of the hippocampus and associated structures. CCK levels were reduced in the septum and hypothalamus. A microdissection analysis indicated that the loss of CCK occurred in nuclei receiving direct projections from the hippocampus and subiculum, suggesting that CCK-containing neurons in the hippocampus and subiculum project to extrahippocampal regions.     

Low intensity tetanic stimulation induces long-term potentiation in hippocampal neurons

A minimal intensity of the stimulation necessary for the induction of long-term potentiation of synaptic transmission (LTP) was investigated by intracellular recording in guinea pig in vitro hippocampal slices. High frequency stimulation of afferent fibres at intensities evoking in CA 1 neurons control excitatory postsynaptic potentials (EPSPs) of amplitudes 1-5 mV, resulted usually in a long-lasting increase in response amplitude. LTP was not observed at lower stimulus strength. The coactivation of a certain, though small number of synaptic contacts is thus necessary for the production of LTP.     

Effect of psychostimulants on responses of neocortical neurons to afferent and subcortical stimuli

The effect of psychostimulants on unit responses of the pericruciate region of the cortex during sensory and subcortical stimulation was studied in experiments on 52 immobilized cats. Amphetamine (2 mg/kg) caused a definite increase in the number of spontaneously active cortical cells. Caffeine (40 mg/kg) had a weaker action. After administration of psychostimulants afferent stimuli more often induced tonic changes in the spontaneous unit activity. More polymodal neurons were found. Phasic responses were often facilitated but were recorded at the same frequency as in the control. Amphetamine and caffeine weakened inhibition of the unit discharges during stimulation of the caudate nucleus and potentiated activation caused by stimulation of the reticular formation. The character of interaction between sensory and reticular (caudate) stimuli was not modulated by the psychostimulants although its scale and intensity were varied. The possible role of the effects of amphetamine and caffeine in therapeutic psychostimulation is discussed.