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

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