Bogovyk R. The role of protease-activated receptors of the first type in the modulation of the activity of rat hippocampal neurons

The dissertation is devoted to the determination of the influence of protease - activated receptors of type 1 (PAR1) on the changes of local potentials in the hippocampus during the development of status epilepticus and on behavioral reactions during the latent and chronic period of epilepsy development in adult rats. The study shows changes in local potentials in the olfactory bulb during the development of status epilepticus (SE), together with the simultaneous registration of local potentials of the hippocampus and amygdala. To conduct these experiments, a four-channel wireless system was developed to record the electrophysiological potentials of the rat brain, which allows recording during epileptic seizures and behavioral tests. Using this system, it was determined that the interictal spikes of neuronal activity, which correspond to the onset of the seizure, appeared earlier in the olfactory bulb and changes in the power of local potentials of the olfactory bulb were much greater than in the hippocampus and amygdala, indicating at a possible role of olfactory bulb in the development of status epilepticus. Changes in the local potentials of the rat hippocampus during the development of status epilepticus in the lithium-pilocarpine model of epilepsy in conditions of inhibition of the function of protease-activated receptors of the first type (surfactant 1) were also studied. Blocking of PAR1 receptors reduced the power of theta and gamma rhythms during the transit phase of status epilepticus, but did not affect changes in rhythm power during the latent phase, indicating a decrease in the hypersynchronization of neural networks before SE formation. The effect of PAR1 blockade on the behavioral responses of rats with status epilepticus was also determined. Studies have been conducted on the locomotor activity of animals, the level of anxiety and emotional memory. Thus, it was determined that the blocking of PAR1 before the formation of status epilepticus, normalizes the level of anxiety and emotional memory in the latent period, and blocking after SE led to an improvement in these indicators in the chronic period of epilepsy. Thus, the study demonstrates not only the involvement of the olfactory bulb in the development of EC, but also the effect of surfactants on the local potentials of the hippocampus during the development of status epilepticus and the involvement of these receptors in regulating the anxiety behavior of epileptic rats. The key role of PAR1-dependent signaling in the formation of fear-induced memory in adult rats has been demonstrated.