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Long-term potentiation (LTP) is a cellular model for learning and memory and believed to be critical for plastic changes in the brain.Depending on the central nervous system region, LTP has been proposed to contribute to many key physiological functions and pathological conditions, such as memory, chronic pain, and drug addiction.While the induction of LTP in general requires activation of postsynaptic glutamate receptors, the expression of LTP can be mediated by postsynaptic mechanisms and/or presynaptic enhancement of glutamate release.In this talk, I will evaluate recent progress made in the mechanisms of LTP in the anterior cingulate cortex (ACC) and explore its functional significance in synaptic changes after peripheral injury..While ACC LTP induced by a pairing protocol is postsynaptically induced and expressed, injury triggered synaptic potentiation in the ACC contains both presynaptic enhancement of glutamate release and postsynaptic potentiation of AMPA receptor-mediated responses.LTP not only takes place in ACC synapses receiving sensory inputs, but also ACC deep neurons that send top-down modulatory influences.Understanding presynaptic and postsynaptic mechanisms for ACC potentiation may help us to treat chronic pain in near future.