Synpatic plasticity is termed as the change of synaptic efficacy, which putatively underlies learning and memory. The direction or degree for synaptic plasticity can be persistently changed by prior synaptic or cellular activity. This plasticity of synaptic plasticity is termed metaplasticity. The mechanism of metaplasticity is not fully understood, especially when the synaptic strength is changed by synaptic activity. Metaplasticity and synaptic plasticity can be induced simultaneously by the same synaptic activity. Therefore, in the synaptic plasticity studies in vitro or in anaesthetized animals in vivo, one hardly predicts the magnitude of LTP or LTD unless the previous activity history of the synapses is known. Here, we have recorded simultaneously the excitatory postsynaptic currents (EPSC) and miniature EPSC (mEPSC) in the Schaffer-CAl synapses in 3-week old Wistar rat slice using whole-cell voltage-clamp techniques. We find an inverse relationship between mEPSC and long-term depression (LTD) induction, in which lower frequency or smaller amplitude of mEPSC is significantly correlated to larger magnitude of LTD. Exposure to behavioral stress immediately before slice preparation or low calcium concentration in bath solution is able to decrease the frequency and amplitude of mEPSC. Under these conditions, the magnitude of LTD does not become significantly larger. However, the frequency or amplitude of mEPSC still inversely correlates to the magnitude of LTD. The correlation coefficient is increased in the stressed condition, but it is decreased by the low calcium bath solution. These findings suggest that the frequency or amplitude of mEPSC may indicate the occurrence of metaplasticity by previous synaptic activity or experience to predict the degree for subsequent LTD induction. Calcium plays a crucial role in synaptic plasticity and metaplasticity. Vanilloid receptor type 1 (VRl, also known as TRPVl), a non-selective cation channel, is expressed widely in brain regions including the hippocampus. Endougenious ligands can activate VRl. It is unclear whether VRl is involved in hippocampal synaptic plasticity. Here we report that the VRl,agonist capsaicin does not affect the basal excitatory postsynaptic currents (EPSC) in the hippocampal CAl area in young rat slice. But it blocks long-term depression (LTD) induction by low frequency stimulation (LFS, 3Hz) and enhances long-term potentiation (LTP) induction by high frequency stimulation (HFS, 200Hz). VRl activation can change the direction of synaptic plasticity, a typical metaplasticity phemomena. Moreover, capsaicin enables LTP induction by HFS at 50Hz that failed to induce LTP in control condition. These are not due to the direct actions of capsaicin on NMDA receptor since it does not affect the NMDA receptor mediated-currents or I-V curve of the currents. Either the CaMKII inhibitor KN-93 or the VRl antagonist capsazepine blocks the actions of capsaicin on the induction of LTP and LTD. These findings suggest that VR1 is able to modulate metaplasticity in the CAl area of the hippocampus, potentially regulating certain types of learning and memory.
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