In the mammalian neural network, synapses are the connection sites of information transfer between neurons. Changes in synaptic strength, called synaptic plasticity, in the form of long-term potentiation (LTP) and long-term depression (LTD), is generally believed to be the cellular mechanism underlying learning and memory. And now, LTP and LTD of excitatory glutamatergic synapses around pyramidal neurons of area CA1, has been studied extensively. α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, as the major receptors to mediate synaptic transmission of excitatory glutamatergic synapses, are necessary for the expression of LTP and LTD. Recent studies have demonstrated that AMPA receptors are continuously recycled between plasma membrane and intra-cellular by means of exocytosis, endocytosis and lateral diffusion. Therefore, regulation of AMPA receptors trafficking results in a rapid change in the number of AMPA receptors on the postsynaptic membrane, then influencing on the expression of either LTP or LTD. In our study, peptides targeted on AMPA receptors have been synthesized by bioinformatics to block LTP/LTD. Using blind whole-cell recordings from CA1 pyramidal neurons in acute hippocampal slice, we find that intracellular application of Pep-A2 can specifically interfere with LTP rather than LTD, and Pep-A3 can specifically affect LTD but not LTP. Also a preliminary investigation of the crucial sites has been carried on, thereby providing a foundation for further studies on the mechanisms of LTP and LTD. Drug addiction, as a pathological learning and memory, is involved with modulation of synaptic plasticity. However, there are few reports on the effect of drug addiction by inhibiting LTP/LTD respectively（Wang YT，2007）. In another study, we find that Tat-A2/Tat-A3 can impair the expression of morphine induced conditioned place preference (CPP), with systemically treating the mice with the Tat-peptides before the test phases of the CPP paradigm. This result suggests that both LTP and LTD are necessary for the expression of morphine CPP. Meantime, it helps us further understand the mechanisms of drug addiction and develop effective medicine.
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