Savotchenko A. Role of endogenous neuraminidase in modulation of network activity in the rat hippocampus

The dissertation thesis is devoted to investigation of modulating role of endogenous neuraminidase in network activity of rat hippocampus. The effect of inhibition of the endogenous NEU activity on the level of PSA expression was estimated using lectin histochemistry. Our data shows that blockade of endogenous neuraminidase activity leads to a rapid extracellular accumulation of PSA. In our study, extracellular field recordings from the CA1 pyramidal layer demonstrated spontaneous recurrent oscillations in 5 of 15 cultured slices at DIV 14-21. About 10-15 min after application of N-Acetyl-2, 3-dehydro-2-deoxyneuraminic acid (NADNA), we observed an increase in the firing frequency. The amplitude of synchronous oscillations also significantly increased. We show that in slices pretreated with endogenous neuraminidase blocker duration of synchronous oscillations induced by gabazine was considerably increased comparatively to control untreated slices. This study adds further information that changes in the level of neuraminidase activity is an important factor, which can affect neuronal network excitability. Acute application of NADNA increases the firing frequency and amplitude of spontaneous synchronous oscillations in low magnesium model of seizures. Seizure-like activity (SLA) recorded from hippocampal slices pretreated with NADNA had a recurrent cycle of activity in the following sequence: initial burst; tonic activity; tonic-clonic activity; and clonic activity. In the untreated slices we did not find a uniform sequence in SLA features. The tonic phase of seizure-like activity in the low magnesium model of ictogenesis was significantly increased in slices pretreated with NADNA. Thus our data indicates that the degree of synchronization is influenced by the amount of active neuraminidase in neuronal tissue. Using the specific blocker NADNA we show that downregulation of endogenous neuraminidase activity causes a significant increase in the level of induced postsynaptic potential in CA1 area of stratum radiatum. During application of neuraminidase blocker, we did not find any significant differences in paired-pulse synaptic plasticity of rat hippocampus. Also the posttetanic potentiation of rat CA1 hippocampus remained intact due to application of specific blocker. To evaluate whether the suppression of neuraminidase activity leads to alteration of long-term potentiation (LTP), we used 100 Hz stimulation of Schaffer collaterals to record field potentials from CA1 stratum radiatum. We show a significant decrease in the level and probability of long-term potentiation of CA1 area in rat hippocampus. We examined the impact of endogenous neuraminidase in short-term depression (STD) and shown the increase of STD level as a result of supressed neuraminidase activity.