Cellular electrophysiological changes in the hippocampus of freely behaving rats during local microdialysis with epileptogenic concentration of N-methyl-D-aspartate

N-methyl-D-aspartate (NMDA) receptor dysfunctions are thought to be involve d in the pathophysiology of seizures of hippocampal origin. While the cellu lar effects of excessive NMDA receptor stimulation have been widely studied in vitro, no data are available on the sequence of cellular electrophysiol ogical events that follow the overstimulation of hippocampal NMDA receptors in awake, behaving subjects. Therefore, the present study addressed this p roblem. Intrahippocampal microdialysis with 500 mu M NMDA was performed in freely behaving rats, and the electrical activity of single neurons in the dialysis area were monitored. In all recorded neurons (n = 9), regardless o f their type, NMDA induced a long-lasting electrical silence preceded in mo st cells by a brief but robust firing rate increase. During these firing ra te increases, place cells lost the spatial selectivity of their discharges, and a gradual reduction in the amplitude of the action potentials was also observed. Remarkably, electroencephalographic (EEG) seizures developed exc lusively after the appearance of cellular electrical silence in the recordi ng/dialysis site. The NMDA-induced electrophysiological changes were revers ible. This study demonstrates that the combined single-cell recording-intra cerebral microdialysis technique can be readily used for inducing focal epi leptiform events in the hippocampus and monitoring the induced cellular ele ctrophysiological events in behaving animals. (C) 2000 Elsevier Science Inc .