Chemogenetic Regulation of the TARP-lipid Interaction Mimics LTP and Reversibly Modifies Behavior
CELL REPORTS(2023)
摘要
Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, is believed to underlie memory formation. Hebbian, postsynaptically expressed LTP requires TARPγ-8 phosphorylation for synaptic insertion of AMPA receptors (AMPARs). However, it is unknown whether TARP-mediated AMPAR insertion alone is sufficient to modify behavior. Here, we report the development of a chemogenetic tool, ExSYTE (Excitatory SYnaptic Transmission modulator by Engineered TARPγ-8), to mimic the cytoplasmic interaction of TARP with the plasma membrane in a doxycycline-dependent manner. We use this tool to examine the specific role of synaptic AMPAR potentiation in amygdala neurons that are activated by fear conditioning. Selective expression of active ExSYTE in these neurons potentiates AMPAR-mediated synaptic transmission in a doxycycline-dependent manner, occludes synaptically induced LTP, and mimics freezing triggered by cued fear conditioning. Thus, chemogenetic controlling of the TARP-membrane interaction is sufficient for LTP-like synaptic AMPAR insertion, which mimics fear conditioning.
更多查看译文
关键词
chemogenetics,lipid,AMPA receptor,auxiliary subunits,phosphorylation,CaMKII,synaptic transmission,synaptic plasticity,fear conditioning,amygdala
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要