神经科学
海马结构
长时程增强
谢弗侧枝
突触可塑性
神经传递
加巴能
莫里斯水上航行任务
γ-氨基丁酸受体
生物
兴奋性突触后电位
受体
抑制性突触后电位
生物化学
作者
Yan Yu,Jingjing Li,Xiao-Qian He,Zi-Ying Lai,Rui Hao,Yu Qi,Dong-Qing Cao,Ming Fu,Hong Ma,Qiyuan Xie,Mu Sun,Zhi‐Li Huang,Lingjing Jin,Huihui Sun,Nonghua Lü,Rui Wang,Wing-Ho Yung,Ying Huang
摘要
As the only ionotropic receptor in the 5-HT receptor family, the 5-HT3 receptor (5-HT3 R) is involved in psychiatric disorders and its modulators have potential therapeutic effects for cognitive impairment in these disorders. However, it remains unclear how 5-HT3 Rs shape synaptic plasticity for memory function.Extracellular as well as whole-cell electrophysiological recordings were used to monitor hippocampal LTP and synaptic transmission in hippocampal slices in 5-HT3 AR knockout or 5-HT3 AR-GFP mice. Immunocytochemistry, qRT-PCR and western blotting were used to measure receptor expression. We also assessed hippocampal dependent cognition and memory, using the Morris water maze (MWM) and novel object recognition.We found that 5-HT3 R dysfunction impaired hippocampal LTP in Schaffer collateral (SC)-CA1 pathway in hippocampal slices, by facilitating GABAergic inputs in pyramidal cells. This effect was dependent on 5-HT3 Rs on axon terminals. It resulted from reduced expression and function of the cannabinoid receptor 1 (CB1 R) co-localized with 5-HT3 Rs on axon terminals, and then led to diminishment of tonic inhibition of GABA release by CB1 Rs. Inhibition of CB1 Rs mimicked the facilitation of GABAergic transmission by 5-HT3 R disruption. Consequently, mice with hippocampal 5-HT3 R disruption exhibited impaired spatial memory in MWM tasks.These results suggest that 5-HT3 Rs are crucial in enabling hippocampal synaptic plasticity via a novel CB1 R-GABAA -dependent pathway to regulate spatial memory.
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