NMDA receptor antagonism blocks experience-dependent expansion of hippocampal "place fields"

In agreement with theories of sequence learning, hippocampal place represen tations expand asymmetrically during repeated route following. This behavio rally induced, experience-dependent expression of neuronal plasticity was b locked by the NMDA(R) antagonist CPP, suggesting that it may result from th e temporal asymmetry and associative properties of LTP. NMDA(R) antagonism, however, had no effect on the range of the progressive shift of firing pha se of hippocampal cells, relative to the theta rhythm, as the rat traverses the cell's "place field." Thus, when place fields normally expand with exp erience, the relationship between firing phase and position is altered, as predicted by models that account for "phase precession" on the basis of asy mmetry of synaptic connection strengths. These effects of CPP mimic changes that occur during normal aging, suggesting mechanisms by which sequence le arning deficits may arise in aged animals.