Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons

Long-term potentiation (LTP) of excitatory transmission in the hippocampus likely contributes to learning and memory. The mechanisms underlying LTP at these synapses are not well understood, although phosphorylation and redis tribution of AMPA receptors may be responsible for this form of synaptic pl asticity. We show here that miniature excitatory postsynaptic currents (mEP SCs) in cultured hippocampal neurons reliably demonstrate LTP when postsyna ptic NMDA receptors are briefly stimulated with glycine. LTP of these synap ses is accompanied by a rapid insertion of native AMPA receptors and by inc reased clustering of AMPA receptors at the surface of dendritic membranes. Both LTP and glycine-facilitated AMPA receptor insertion are blocked by int racellular tetanus toxin (TeTx), providing evidence that AMPA receptors are inserted into excitatory synapses via a SNARE-dependent exocytosis during LTP.