ИСТИНА

In this study we investigated the effect of memory-enhancing and anxiolytic prolin-containing dipeptide Noopept (NP) on spontaneous and evoked synaptic activity of CA1 pyramidal cells in rat's hippocampal slices. NP was synthesized as peptide analog of piracetam which is known as one of the most efficient memory-enhancing drugs (Giurgea, 1972; Winblad, 2005). NP is similar to piracetam in its chemical structure and functional characteristics, but displays its effects in much lower concentration (Ostrovskaya et al, 2006). Firstly, we examined the effect of NP on spontaneous IPSCs in CA1 pyramidal cells using patch-clamp technique in whole-cell configuration. NP (1µM) increased spike-dependent release of GABA from terminals of inhibitory interneurons. It was manifested in the increase of amplitude and frequency of spontaneous TTX-sensitive sIPSCs, whereas TTX-non sensitive mIPSCs remained unchanged. In current-clamp experiments we found that this effect resulted in the decrease of spontaneous spike activity of pyramidal cells and the increase of activity of a set of inhibitory interneurons resigning in stratum radiatum. In these cells NP induced a 2-3 fold increase of spiking rate that was accompanied by depolarization of cell membrane by 3-5 mV. Further, NP increased the probability of spikes evoked by stimulation of Shaffer collaterals in CA1 pyramidal cells. Thus, NP inhibits spontaneous activity of pyramidal neurons and facilitates their evoked responses, that could be interpreted as the increase of signal to noise ratio. One may speculate that these synaptic events mediated by NP underlines its nootropic activity. Supported by: Supported by: Russian Science Foundation (Grant 16-15-00235).