Postsynaptic NMDA receptor-mediated calcium accumulation in hippocampal CAl pyramidal cell dendrites

IN the CAl hippocampal region, intracellular calcium is a putative second messenger1,2 for the induction of long-term potentiation (LTP), a persistent increase of synaptic transmission produced by high frequency afferent fibre stimulation3. Because LTP in this region is blocked by the NMDA (N-methyl-D-aspartate) receptor antagonist AP5 (DL-2-amino-5-phosphonovaleric acid) (ref. 4) and the calcium permeability of NMDA receptors is controlled by a voltage-dependent magnesium block5,6, a model has emerged that suggests that the calcium permeability of NMDA receptor-coupled ion channels7–10 is the biophysical basis for LTP induction11–15. We have performed microfluorometric measurements16 in individual CAl pyramidal cells during stimulus trains that induce LTP. In addition to a widespread component of postsynaptic calcium accumulation previously described17, we now report that brief high frequency stimulus trains produce a transient component spatially localized to dendritic areas near activated afferents. This localized component is blocked by the NMDA receptor antagonist AP5. The results directly confirm the calcium rise predicted by NMDA receptor models of LTP induction.