The hippocampal area Cornu Ammonis (CA) CA2 is important for social interaction and is innervated by Substance P (SP)-expressing supramammillary (SuM) nucleus neurons. SP exerts neuromodulatory effects on pain processing and central synaptic transmission. Here we provide evidence that SP can induce a slowly developing NMDA receptor- and protein synthesis-dependent potentiation of synaptic transmission that can be induced not only at entorhinal cortical (EC)-CA2 synapses but also at long-term potentiation (LTP)-resistant Schaffer collateral (SC)-CA2 synapses. In addition, SP-induced potentiation of SC-CA2 synapses transforms a short-term potentiation of EC-CA2 synaptic transmission into LTP, consistent with the synaptic tagging and capture hypothesis. Interestingly, this SP-induced potentiation and associative interaction between the EC and SC inputs of CA2 neurons is independent of the GABAergic system. In addition, CaMKIV and PKMζ play a critical role in the SP-induced effects on SC-CA2 and EC-CA2 synapses. Thus, afferents from SuM neurons are ideally situated to prime CA2 synapses for the formation of long-lasting plasticity and associativity.

中文翻译：

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P物质在大鼠海马区CA2诱导可塑性和突触标记/捕获

海马区Cornu Ammonis（CA）CA2对于社交互动很重要，并且受表达P物质（SP）的上乳（SuM）核神经元的支配。SP对疼痛处理和中枢突触传递发挥神经调节作用。在这里，我们提供证据表明SP可以诱导缓慢发展的NMDA受体和蛋白质合成依赖性的突触传递增强，这种增强不仅可以在内嗅皮层（EC）-CA2突触中诱导，而且可以在长期增强（LTP）耐药性中诱导Schaffer侧支（SC）-CA2突触。此外，SP诱导的SC-CA2突触增强将EC-CA2突触传递的短期增强转化为LTP，这与突触标记和捕获假设相符。有趣的是，SP诱导的CA2神经元的EC和SC输入之间的增强和相关相互作用独立于GABA能系统。此外，CaMKIV和PKMζ在SP诱导的SC-CA2和EC-CA2突触中起关键作用。因此，来自SuM神经元的传入分子处于理想的位置，可以引发CA2突触，从而形成持久的可塑性和缔合性。