突触相关蛋白SIP30介导神经病理性痛情绪反应和相关记忆的突触机制

我们前期在脊髓水平的研究首次揭示SIP30作为ERK和CREB的下游靶标特异性介导神经病理性痛的发生和发展，同时，在皮层水平的研究证明前扣带皮层（ACC）内ERK/CREB信号通路参与痛厌恶情绪的形成。我们最近的研究进一步提示，SIP30在ACC的表达参与神经病理性痛诱导的痛厌恶情绪的形成，SIP30对ACC神经元突触传递的影响可能是该作用产生的细胞机制。我们提出如下研究假说：外周神经损伤引起伤害性信息经脊髓传入到脑，激活ACC脑区，上调SIP30表达水平；SIP30进一步通过突触前机制增加兴奋性神经递质（如谷氨酸）在ACC内的释放，或/和通过突触后机制（如通过SIP30结合蛋白或神经调质）调控AMPA或NMDA受体的功能，从而介导痛厌恶情绪和相关记忆的产生。通过本研究，我们将揭示SIP30介导痛厌恶情绪和相关记忆形成的突触机制，明确参与调控SIP30的胞内信号分子、相关蛋白和递质/调质。

Our previous study at the spinal cord level, for the first time, discovered that SIP30, as a downstream target of ERK and CREB, specifically mediates the establishment and maintenance of neuropathic pain. In the meanwhile, we found that, at the cortex level, ERK/CREB signaling pathway in the rACC is necessary for pain-related aversion. More recently, we also found that SIP30 is also involved in the formation of neuropathic pain induced aversive (or repulsive) emotion and related memory. We hypothesized that SIP30 is up-regulated in ACC by the signal of peripheral nerve damage, which in turn increases the release of excitatory neurotransmitters from ACC neuron through pre-synaptic mechanism, and/or regulates the functions of AMPA and NMDA receptors through post-synaptic mechanism; therefore, mediates the formation of pain related aversive (or repulsive) emotion and memory. Our proposed study will unveil the mechanism of SIP30 involvement in the formation of pain related aversive (or repulsive) emotion and memory, and elucidate the molecular players that are involved in SIP30 function.