CONDITIONS FOR THE INDUCTION OF LONG-TERM POTENTIATION AND LONG-TERM DEPRESSION BY CONJUNCTIVE PAIRING IN THE DENTATE GYRUS IN-VITRO

The conditions under which long-term potentiation (LTP) and long-term depression (LTD) of excitatory postsynaptic currents were induced by t he conjunctive pairing-type protocol of afferent stimulation and post synaptic depolarization were studied in the medial perforant pathway-g ranule cell synapse of the dentate gyms in vitro. The conjunctive pair ing of I-Hz afferent stimulation and steady state postsynaptic depolar ization to 0 mV did not induce LTP or LTD. Inhibition of LTD induction with a phosphatase inhibitor or ruthenium red resulted in induction o f LTP after the conjunctive pairing. Such LTP induction was N-methyl-D -aspartate dependent. Conversely, inhibition of LTP induction with a k inase inhibitor resulted in LTD induction after the conjunctive pairin g. Thus the failure to induce LTP or LTD with the pairing protocol inv olving depolarization to 0 mV membrane potential was due to simultaneo us activation of intracellular processes that generate the induction o f LTP and LTD. Increasing the frequency of afferent stimulation to 200 Hz, even for just eight stimuli, resulted in LTP induction. The studi es show that two factors govern the induction of LTP/LTD, membrane pot ential and frequency of afferent stimulation, with either increased de polarization or increased afferent stimulation favoring LTP induction.