声音强度信息认知的突触微环路

Previous auditory study mainly performed in anaesthetized animals except for bat. However, sound isn’t been percepted in unconscious condition (i.e., anaesthesia). It is unexplored the microsynaptic circuits underlying the perception of sound information and its meaning. We found neurons mainly in the hippocampus CA3 only responsed monotonicaly to noise intensity in awake mouse, but not in anesthetized. The response patterns from PSTH could be invided two types: short- and long-delay types. Long-delay type may be related to perception of sound specific meaning acording to previous studies, and short-delay type may percept sound intensity information. Morphologic evidences show two pathways underlying auditory information processing in hippocampus: the lemniscal excitatory entorhinal-hippocampal pathway and the non-lemniscal inhibitory septohippocampal pathway. However, there is little functional evidence. Based on the previous studies and our preliminary experiments, we hypothesize that hippocampus integrates the orignal fractional frequency information from excitatory entorhinal-hippocampal and inhibitory septohippocampal inputs, and differentially gates perception of sound intensity information by selectly increasing excitatory inputs and decreasing inhibitory inputs for conditioned sound intensity. We partially confirmed this hypotheses by whole-cell recordings in vivo from awake fear conditioning mice. Therefore, we are going to systematically reveal the mechanism underlying perception of sound intensity information by loose patch and whole cell recording in vivo in awake animals, with opotogenetics, behavioral, immunohistological and pharmacological technics.

前期听觉系统研究除蝙蝠外多为麻醉动物。但在麻醉等无意识状态下没有声音认知。受技术限制声音认知的突触机制尚无研究。我们探查广泛脑区发现海马CA3在麻醉状态下没有声反应，在清醒状态下只对噪声呈长、短延时型反应。结合文献我们认为长延时型与声音特定意义认知相关，短延时型反映声音强度认知。尽管形态学依据显示海马接受脑干和内嗅皮层的输入，且认为海马经特异性和非特异性丘系投射处理声音信息，但尚无突触微环路的研究。而我们预实验已成功解析出其兴奋性和抑制性突触输入。故我们假说：海马CA3整合听觉原始分频信息，在有意识条件下，经特殊事件选择性改变内嗅-海马兴奋性输入和脑干-海马抑制性输入，从而差分门控声音信息认知。我们已通过声恐惧模型部分证实了这一假说。本课题拟通过清醒小鼠在体膜片钳记录，以及光遗传学、行为学、免疫组化和药物干预等方法，系统揭示声音信息及其代表意义认知的细胞和突触机制。

前期听觉系统研究除蝙蝠外多为麻醉动物。但在麻醉等无意识状态下没有声音认知。受技术限制声音认知的突触机制尚无研究。我们探查广泛脑区发现海马CA3在麻醉状态下没有声反应，在清醒状态下只对噪声呈长、短延时型反应。结合文献我们认为长延时型与声音特定意义认知相关，短延时型反映声音强度认知。我们假说：海马CA3整合听觉原始分频信息，在有意识条件下，经特殊事件选择性改变内嗅-海马兴奋性输入和脑干-海马抑制性输入，从而差分门控声音信息认知。我们已通过声恐惧模型，经清醒小鼠在体膜片钳记录，以及光遗传学、行为学、免疫组化和药物干预等方法，按计划系统揭示了声音信息在海马-内嗅的声反应及突触机制，还将课题分别延伸到前额叶和听觉系统的声反应特性与意义。发现一条新的声处理通路：来自脑干网状结构再经隔核、内嗅皮层到海马投射的噪声反应通路，发现一种可能与提高前额叶声反应的信噪比有关的增强特异性记忆的比较学习方法；解析了清醒动物下丘双耳声讯信息处理的突触微环路，发现下丘双声反应取决于下位核团整合并起到同侧或对侧输入信息的转换作用。在cereb cortex, frontier in neuroscienc等国际同领域期刊发表原创性科研论文9篇，其中一区论文1篇，二区论文6。远超过了当初预期的SCI收录论文3-5篇。为声信息的认知和双耳听觉提供新理论，为神经系统信息加工提出新视角。培养青年教师3人，博士生10人，硕士生12人。其中6我获自然科学基金面上和青年项目支助；8人赴美国和加拿大联合培养2年以上。