Effects of ketamine on selective long-term potentiation in the piriform cortex

Previous research in our laboratory has demonstrated a selective long-term potentiation (LTP) of the piriform cortex (PC) potential evoked by olfactory bulb stimulation following repeated administration of high-frequency trains. Period 1 of the evoked potential represents both a monosynaptic EPSP produced by activation of the lateral olfactory tract and a disynaptic EPSP produced by an extensive association fiber system. Period 1 remains unchanged following administration of LTP trains, while period 2, which is temporally associated with IPSPs, is dramatically increased in amplitude and duration.;This research tests the hypotheses that NMDA receptors mediate both the induction and expression of selective LTP in the piriform cortex. Ketamine (an NMDA antagonist) or saline was administered to separate groups of male Long-Evans rats immediately prior to each of 4 sets of potentiating rains. The saline group exhibited normal amounts of both short- and long-term potentiation of period 2, but the ketamine group failed to potentiate. These results are consistent with the hypothesis that activation of NMDA receptors is necessary for induction of selective LTP. The effects of ketamine in fully potentiated animals indicate that NMDA receptors are also involved in the expression of selective LTP, although they appear to play a lesser role in the short-term (5-15 min post-trains), as compared to the long-term (;The results of this research, together with previous research on selective LTP and research documenting the specificity of ketamine's effects on NMDA receptors, indicate that the most likely mechanism by which ketamine blocks induction of selective LTP is through antagonism of NMDA receptors at PC association fiber synapses. A hypothesis is proposed that selective LTP reflects a long-term increase, mediated by NMDA receptors, in the efficacy of association fiber synapses on inhibitory interneurons in the PC.