Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 597.
Neurobiology/Aging Program, Life Sciences Institute, National University of Singapore, Singapore 117 456.
Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8741-E8749. doi: 10.1073/pnas.1711267114. Epub 2017 Sep 25.
The hippocampal area (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.
海马区（CA）CA2 对社交互动很重要，它由表达 P 物质（SP）的上乳突核神经元支配。SP 对疼痛处理和中枢突触传递具有神经调节作用。在这里，我们提供的证据表明，SP 可以诱导 NMDA 受体和蛋白质合成依赖性的突触传递的缓慢发展的增强，这种增强不仅可以在海马脑区（EC）-CA2 突触上诱导，也可以在长期增强（LTP）抵抗的 Schaffer 侧枝（SC）-CA2 突触上诱导。此外，SP 诱导的 SC-CA2 突触的增强将 EC-CA2 突触传递的短期增强转化为 LTP，与突触标记和捕获假说一致。有趣的是，这种 SP 诱导的 CA2 神经元 EC 和 SC 输入之间的增强和关联相互作用与 GABA 能系统无关。此外，CaMKIV 和 PKMζ 在 SP 对 SC-CA2 和 EC-CA2 突触的作用中起着关键作用。因此，来自 SuM 神经元的传入神经可以使 CA2 突触为形成持久的可塑性和关联性做好准备。
