MANIPULATION OF PYRAMIDAL CELL FIRING IN THE HIPPOCAMPUS OF FREELY BEHAVING RATS BY LOCAL APPLICATION OF K+ VIA MICRODIALYSIS

In this study, microdialysis was performed in the hippocampus of freel y behaving rats, and the firing of pyramidal cells, including place ce lls, was recorded at the site of the microdialysis probe. For 10-min p eriods, the artificial cerebrospinal fluid (ACSF) in the microdialysis system was replaced with ACSF containing 50 mM K+ (high K+ solution). Complementary in vitro tests determined that microdialysis with such high K+ solution produced an outflow of 5% of the perfused K+ from the microdialysis probe. Application of K+ with this method into the CA1 region significantly increased the firing of the local pyramidal cells , including place cells, during both movement and sleep. On average, K + exposures increased the firing rate of the neurons to 306% and 448% of the control firing rate during movement and sleep, respectively. Af ter the termination of the K+ outflow, the cells continued to discharg e for 5-30 min with a significantly higher frequency than before the K + challenge. This phenomenon also occurred in both behavioral states. During the period of enhanced firing, the out-of-field firing rate of the recorded place cells was dramatically increased. It was also found that during the K+ applications, otherwise silent pyramidal cells oft en became electrically active. The K+-induced firing modifications wer e usually not accompanied by behavioral or EEG changes. The data raise the possibility that transient elevations in the extracellular K+ con centration contribute to the ionic/molecular processes which are respo nsible for plastic firing pattern modifications in hippocampus. Pharma cological manipulation of place cells with the described method offers a new strategy to understand the molecular bases of spatial memory. ( C) 1996 Wiley-Liss, Inc.