Nmda Receptordependence Of

Baseline excitatory synaptic transmission in the CNS, including at Schaffer-collateral synapses, depends on a glutamate-gated cation channel, the AMPA subtype of glutamate receptor (see Box 1). This is the basic housekeeping glutamate receptor that mediates most of excitatory synaptic transmission in the brain. In 1983 Graham Collingridge made the breakthrough discovery that induction of tetanus-induced forms of LTP are blocked by blockade of a different subtype of glutamate receptor, the N-methyl-D-aspartate (NMDA) receptor (5). Collingridge's fascinating discovery was that the glutamate analog amino-phosphono-valeric acid (APV), an agent that selectively blocks the NMDA subtype of glutamate receptors, could block LTP induction while leaving baseline synaptic transmission entirely intact (Figure 6).

This was the first experiment to give a specific molecular insight into the mechanisms of LTP induction. The properties of the NMDA receptor that allow it to function in this unique role of triggering LTP are important, and we will return to a detailed analysis of regulation of the NMDA receptor several times in this book. For our purposes right now, suffice it to say that pharmacologic blockers of NMDA receptor function have allowed the definition of different types of LTP that can be selectively induced with various physiologic stimulation protocols. For example, subsequent

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