Activation of TRPC1 Channel by Metabotropic Glutamate Receptor mGluR5 Modulates Synaptic Plasticity and Spatial Working Memory.
Activation of TRPC1 Channel by Metabotropic Glutamate Receptor mGluR5 Modulates Synaptic Plasticity and Spatial Working Memory.
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DOI：
10.3389/fncel.2018.00318
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发表时间：
2018
影响因子：
5.3
通讯作者：
Gailly P
中科院分区：
文献类型：
--
作者：
Lepannetier S;Gualdani R;Tempesta S;Schakman O;Seghers F;Kreis A;Yerna X;Slimi A;de Clippele M;Tajeddine N;Voets T;Bon RS;Beech DJ;Tissir F;Gailly P
I组代谢型谷氨酸受体，特别是mGluR 5，已经涉及各种形式的突触可塑性，这些突触可塑性被认为是陈述性记忆的基础。我们观察到mGluR 5特异性激活含有TRPC 1的通道，TRPC 1是在海马CA 1 -3区高度表达的瞬时受体电位（TRPC）通道的典型家族的同种型。TRPC 1能够与TRPC 4和/或TRPC 5同种型形成四聚体复合物。TRPC 1/4/5复合物最近已参与海马中突触传递的效率。因此，我们使用TRPC 1表达缺乏的小鼠模型来研究mGluR 5-TRPC 1通路在突触可塑性和记忆形成中的参与。trpc 1-/-小鼠表现出空间工作记忆和恐惧条件反射的改变。mGluR的激活增加了WT神经元的突触兴奋性，但Trpc 1-/-小鼠的突触兴奋性没有增加。在Trpc 1-/-小鼠的脑切片中，由θ爆发触发的LTP不能随着时间的推移而维持。mGluR诱导的LTD在这些小鼠中也受损。最后，Pico 145对分离的神经元或脑切片的TRPC 1的急性抑制模拟了Trpc 1的遗传耗竭，并抑制了mGluR诱导的阳离子进入以及随后对突触可塑性的影响，不包括Trpc 1-/-小鼠的发育或代偿机制。总之，我们的研究结果表明TRPC 1在突触可塑性和空间工作记忆过程中发挥作用。
Group I metabotropic glutamate receptors, in particular mGluR5, have been implicated in various forms of synaptic plasticity that are believed to underlie declarative memory. We observed that mGluR5 specifically activated a channel containing TRPC1, an isoform of the canonical family of transient receptor potential (TRPC) channels highly expressed in CA1-3 regions of the hippocampus. TRPC1 is able to form tetrameric complexes with TRPC4 and/or TRPC5 isoforms. TRPC1/4/5 complexes have recently been involved in the efficiency of synaptic transmission in the hippocampus. We therefore used a mouse model devoid of TRPC1 expression to investigate the involvement of mGluR5-TRPC1 pathway in synaptic plasticity and memory formation. Trpc1-/- mice showed alterations in spatial working memory and fear conditioning. Activation of mGluR increased synaptic excitability in neurons from WT but not from Trpc1-/- mice. LTP triggered by a theta burst could not maintain over time in brain slices from Trpc1-/- mice. mGluR-induced LTD was also impaired in these mice. Finally, acute inhibition of TRPC1 by Pico145 on isolated neurons or on brain slices mimicked the genetic depletion of Trpc1 and inhibited mGluR-induced entry of cations and subsequent effects on synaptic plasticity, excluding developmental or compensatory mechanisms in Trpc1-/- mice. In summary, our results indicate that TRPC1 plays a role in synaptic plasticity and spatial working memory processes.
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影响因子：
5.1
作者：
Du, Lai-Ling;Wang, Lin;Zhou, Xin-Wen
通讯作者：
Zhou, Xin-Wen
影响因子：
4.7
作者：
Fitzjohn, SM;Kingston, AE;Collingridge, GL
通讯作者：
Collingridge, GL
影响因子：
4
作者：
GAILLY, P;BOLAND, B;GILLIS, JM
通讯作者：
GILLIS, JM
影响因子：
3
作者：
Anderson, William W.;Collingridge, Graham L.
通讯作者：
Collingridge, Graham L.
影响因子：
5.5
作者：
De Backer, F;Vandebrouck, C;Gillis, JM
通讯作者：
Gillis, JM