STIMULATION ON THE POSITIVE PHASE OF HIPPOCAMPAL THETA-RHYTHM INDUCESLONG-TERM POTENTIATION THAT CAN BE DEPOTENTIATED BY STIMULATION ON THE NEGATIVE PHASE IN AREA CA1 IN-VIVO

Long-term potentiation (LTP) of synaptic transmission induced by high- frequency stimulation (HFS) is considered to be a model for learning p rocesses; however, standard HFS protocols consisting of long trains of HFS are very different from the patterns of spike firing in freely be having animals. We have investigated tile ability of brief bursts of H FS triggered at different phases of background theta rhythm to mimic m ore natural activity patterns. We show that a single burst of five pul ses at 200 Hz given on the positive phase of tail pinch-triggered thet a rhythm reliably induced LTP in the stratum radiatum of the hippocamp us of urethane-anesthetized rats. Three of these bursts saturated LTP, and 10 bursts occluded the induction of LTP by long trains of HFS, Bu rst stimulation on the negative phase or at zero phase of theta did no t induce LTP or long-term depression. In addition, stimulation with 10 bursts on the negative phase of theta reversed previously established LTP. The results show that the phase of sensory-evoked theta rhythm p owerfully regulates the ability of brief HFS bursts to elicit either L TP or depotentiation of synaptic transmission. Furthermore, because co mplex spike activity of approximately five pulses on the positive phas e of theta rhythm can be observed in freely moving rats, LTP induced b y the present theta-triggered stimulation protocol might model putativ e synaptic plastic changes during learning more closely than standard HFS-induced LTP.