Ⅰ Contribution Of Postsynaptic NMDA Receptors To In Vivo Burst Spiking Of Hippocampal CA1Pyramidal CellsⅡ Time Window Of Fear-memory Extinction

The hippocampus is a key brain area of learning and memory, and spontaneous activity of hippocampal neurons is thought to be critical for learning and memory. In vivo study of hippocampal spontaneous activity characteristics and its mechanisms pave the way to understand hippocampal memory function and to solve key questions on hippocampus related diseases. Previous studies have found that the spontaneous activity in the hippocampus consists of a large number of complex burst spikes (CBs), which are attributed to be the neural basis of hippocampus-dependent memory acquisition and the subsequent process of memory consolidation. However, the cellular and molecular mechanisms accounting for the hippocampal CBs remained largely unknown. In this study, we perform in vivo patch-clamp recording from hippocampal CA1pyramidal cells in anesthetized rats, and observed the CBs that were similar to previous demonstration by extracellular recording. The frequency of CBs ranged from0. Olto2.88Hz (0.46±0.75, mean±SD); Each CBs in individual cells usually composed2-5action potential (AP) discharges. By applying NMDA receptor antagonist MK801through the recording pipette, we found that the proportion of CBs is significantly reduced, particularly in the CBs with4and5APs, while the proportions of the CBs with2and3Aps as well as the single spiking were not significantly changed. Thus, we conclude that the spontaneous multi-^eaks CBs of hippocampal CA1pyramidal cells depends on postsynaptic NMDA receptors, and propose a new mechanism of NMDA receptors used by the hippocampus for learning and memory, which relies on the CB activity. Once acquired, early memory is subsequently consolidated to be permanent memory. With respect to fear memory, numerous studies have examined the extinction process as well as the underlying mechanisms, particularly regarding treating post-traumatic stress disorder (PTSD).Whether this type of fear memory can be extinct without or only within a limited time window remains controversial. we redesigned the extinction experiment by differentiate the time window between the extinction and the fear conditioning in four groups:1hour,24hours,72hours and7days after trace fear conditioning, and then test their Forgotten Index in short-term (1day after Extinction) and long-term (3weeks after Extinction) respectively. The Result shows that all groups achieved evenly good extinction effect in the short term (1hour group is relatively poor) and long-term (three weeks after extinction without a sign of spontaneous recovery). Since the baseline forgotten index of each extinction group verify due to different time span, it may cause the difference in extinction effect among four groups. To separate contextual fear memory from emotion, we induce re-train experiment (2times of CS-US pairing) and found72hours group showed significant better maintaining of extinction while other group show no significant difference with control group. That is to say, after3weeks of success extinction of fear memory, if fear event ever strikes again, rats cannot sustain their first extinction effectively except the72hour group. This result indicates that the fear memory has a clear time window after associative conditioning, which requires a precise period of time (72hours after fear conditioning) to be effectively disassociated, namely, extinct.