[Detection of c-fos expression in animal brain in a pilocarpine model of temporal lobe epilepsy].

The dynamics of the involvement of different brain structures in a pathological process is very important for decoding the mechanisms of temporal lobe epilepsy. In this work, the experimental model of temporal lobe epilepsy induced by lithium chloride and pilocarpine was used. The method of immunochemical detection of the immediate early gene c-fos was used as an indicator of functioning neurons in the brain. The c-fos expression was determined at different time points (30, 60 and 90 min) after the pilocarpine injection. An increase in the c-fos expression was observed in neuronal populations during the development of the status epilepticus, the time and degree of involvement of different brain structures being different. The expression of c-fos was first observed in the piriform cortex, the olfactory tubercle, thalamic nuclei, lateral habenular nuclei, and the caudate putamen. Then the hippocampus, the septal formation, the amygdala, and basal ganglia were involved in the activation process. In the hypothalamic areas, c-fos expression was observed latest. These data contribute to understanding the mechanisms of temporal lobe epilepsy and searching for the ways of its therapy.

[Changes in the electrical activity of the medial septal region, piriform cortex and amygdala during epileptogenesis in the model of temporal lobe epilepsy].

Local field potentials (EEGs) in the medial septal area, amygdala and piriform cortex were recorded in waking guinea pigs in the control and during epileptogenesis in the model of chronic temporal lobe epilepsy (lithium-pilocarpin model of status epilepticus). Analysis of changes in rhythmical activity and interstructural relations was carried out at different stages of epileptogenesis. Increased frequency of rhythmic activity in delta, theta, and alphabands was observed during epileptogenesis. Correlation relations between the activities of the medical septum with the piriform cortex and amygdala clearly decreased to 5 months after development of status epilepticus. Changes in the frequency of oscillations and structural correlations developed in time from two months on and reached a maximum 5 months after the status epilepticus development. It point to intensification of the pathological changes during formation of the epileptic focus. A possible role of the observed EEG changes in the formation of a pathological centre is discussed.

[Coherence and phase analysis of theta-oscillations in the septohippocampal system during seizures].

Interrelations of the hippocampus and medial septal area (MSA) in the theta band (4-8 Hz) were studied during seizures produced by electrical kindling in waking guinea pigs. Field activity (EEG) was analyzed using the wavelet transform. A decrease in coherence of theta-oscillations in the hippocampus and MSA was observed during seizures. Phase analysis showed that in the beginning of kindling the MSA led in phase, but after formation of the pathological focus, MSA lagged the hippocampus. The data may contribute to understanding mechanisms of temporal lobe epilepsy.

Correlational relationships between the hippocampus and medial septal area and their changes during epileptogenesis.

EEG traces were recorded from the hippocampus and medial septal area of conscious guinea pigs in control conditions and on repeated stimulation of the perforant path. Changes in the correlations of activity in these structures during stimulation-evoked convulsions (a model of acute epilepsy) and during the process of epileptogenesis (a model of chronic epilepsy) were analyzed. A high correlation between baseline activity in the hippocampus and medial septal area seen in control conditions decreased sharply with the appearance of acute and chronic convulsions. Kindling led to hippocampus-independent generation of field convulsive discharges in the medial septal area. During kindling, there was a gradual disintegration of activity in the hippocampus and septum, which provides evidence for impairment of the operation of the septo-hippocampal network during epileptogenesis.

[Relationships between the hippocampus and medial septal region and their alterations during epileptogenesis].

EEGs of the hippocampus and the medial septal region (MSR) in the control conditions and during repeated stimulation of the perforant path were simultaneously recorded in awake guinea pigs. Changes in correlation of activity of these structures during seizures provoked by the stimulation (model of acute epilepsy) and in the process of epileptogenesis induced by the kindling (model of chronic epilepsy) were analyzed. A high correlation of the baseline activities of the hippocampus and MSR observed in the control sharply decreased during acute and chronic seizures. Kindling led to emergence of the MSR capability of hippocampus-independent generation of the field seizure discharges. In the process of kindling the progressive disintegration of activities of the hippocampus and the MSR was revealed being indicative of disorders in functioning of the septohippocampal network during epileptogenesis.

[Medial septal region as a target for modulation of seizure discharges in the hippocampus in a model of acute temporal lobe epilepsy].

Investigation of changes in the hippocampal EEG produced by GABAergic and cholinergic substances delivered into the medial septum region was performed in awake rabbits. Changes in the threshold of seizure discharges in the hippocampus evoked by perforant path stimulation (model of acute epilepsy) were also examined. Injections of GABAA receptor antagonist picrotoxin or agonist of cholinergic receptors carbacholine in low doses induced an increase in the power of delta- and theta modulation and appearance of 7-12-Hz oscillations. The threshold of hippocampal seizure afterdischarges decreased. In higher doses, these substances evoked 7-15-Hz oscillations followed by seizures. GABAA receptor agonist muscimol and muscarinic receptor antagonist scopolamine decreased the power of the theta rhythm and increased the seizure threshold. Picrotoxin or carbacholine injected after muscimol or scopolamine, respectively, did not evoke seizures. Thus, we have shown the possibility to control hippocampal activity by local changes in the GABAergic and cholinergic systems of the medial septum region.