ИСТИНА

The aim of this study was to investigate whether novel prolin- containing dipeptide Noopept ( NP) influences synaptic transmission in central neurons. NP was synthesized as peptide analog of piraсetam which is known as one of the first generation nootropics racetam group (Giurgea, 1972; Winblad, 2005). NP is similar to piracetam in its chemical structure and memory- enhancing ability but displays the effect in much lower concentration. In addition to nootropic activity NP also displays an anxiolitic effect (Ostrovskaya et al, 2006). We examined the effect of NP on spontaneous and evoked IPSCs in CA1 pyramidal cells in rat hippocampal slices using patch-clamp technique in whole- cell configuration. It was found that NP( 1µM) increased spike- dependant release of GABA from terminals of inhibitory interneurons on CA1 pyramidal cells. The effect manifested itself in the increase of amplitude and frequency of spontaneous TTX-sensitive sIPSCs whereas TTX- non sensitive mIPSCs remained unchanged. We also found that IPSCs evoked by Shaffer collaterals stimulation, either short -latency (feed- forward), or long- latency (feed-back) ones increased after NP application. We hypothesized that NP directly excited inhibitory interneurons which terminate on CA1 pyramidal cells. To check this hypothesis we performed current clamp egistration of several (n =5) interneurons resigning in stratum radiatum (SR). In all cases NP induced a 2-3 fold increase of spiking rate that was accompanied by depolarization of cell membrane to 3-5 mV. In the experiments with direct measurement of neuronal [Ca2+]i in hippocampal organotypic slices we revealed that NP selectively increased [Ca2+]i activity in SR interneurons without significantly changing it in stratum pyramidal neurons. Taken together these date clarify that the target of NP action is inhibitory interneurons located in SR of hippocampus. Supported by: Russian Scientific Foundation (Grant 16-15-00235).