Frequency dependence of long-term potentiation and depression in the dentate gyrus of the freely moving rat.

Abstract

Long-term potentiation (LTP) or long-term depression (LTD) can be produced in the dentate gyrus (DG) of the hippocampus with high-or low-frequency stimulation trains, respectively. Although LTP can be elicited in a variety of preparations, we know of no reports of LTD unaccompanied by seizure activity in the awake rat. In this experiment, test pulses at alternating high (95% of maximum response) and moderate (50-75% of maximum) intensities were presented at 0.05 Hz to the perforant path of freely moving rats in order to assess changes in DG population spike amplitude. Trains were delivered at 10-min intervals, and intratrain frequency was adjusted either upward from 3 Hz or downward from 400 Hz until all subjects had received three consecutive tetani at each of 3, 6, 12.5, 25, 50, 100, 200, and 400 Hz. Potentiation was observed at high frequencies regardless of whether ascending (ASC) or descending (DES) test order was used. Depression occurred at low frequencies, but only in ASC rats. The LTD observed in this preparation was not very robust and was clearly seen only when moderate-intensity test pulses were used. The threshold frequency (at which depression gives way to potentiation) was approximately 6-9 Hz for DES rats but was 100-120 Hz for ASC animals. Prior stimulation therefore affected the response to subsequent trains. These results are generally consistent with the hypothesis of a variable threshold for LTP induction. Our findings can also be explained by postulating a wide "labile range" at moderate frequencies within which no plastic changes occur.