Postsynaptic mechanisms of induction of NMDA-dependent long-term post-tetanic potentiation of synaptic transmission

Abstract

Experiments on hippocampus slices of rats showed that the pattern of induction of long-term post-tetanic potentiation of synaptic transmission is determined by the frequency of tetanic stimulation of Schaffer collaterals. With their high-frequency (>10/sec) stimulation, a phase of reversible increase in the amplitude of population EPSP (pEPSP) is observed within the initial 30-min-long interval; it is related to an increase in the intracellular Ca2+ concentration resulting from simultaneous activation of NMDA and metabotropic glutamate receptors and voltage-activated calcium channels. With the participation of calmodulin, Ca2+ activate Ca2+-calmodulin-dependent protein kinase II. The latter phosphorylates AMPA/kainate receptors (their kainate-responsive compartments), which promotes an increase in their chemosensitivity. Under conditions of low-frequency (<10/sec) tetanic stimulation of synaptic inputs, for the same reasons, an increase in the intradendritic Ca2+ concentration exerts no expressed influence on protein kinase II, but activates calcineurin. The latter, with the involvement of other phosphoprotein phosphatases, dephosphorylates AMPA/kainate receptors and turns some of them into the refractory state; this is expressed in a reversible depression of pEPSP. After 30 min of either high-frequency, or low-frequency stimulation, a non-decremental phase of long-term post-tetanic potentiation develops, which is related to the increase in the protein kinase C activity, phosphorylation of the AMPA-responsible compartments of AMPA/kainate receptors, their rising sensitivity, and a stable increase in the pEPSP amplitude