期刊
MOLECULAR NEUROBIOLOGY
卷 57, 期 3, 页码 1332-1346出版社
SPRINGER
DOI: 10.1007/s12035-019-01828-x
关键词
TREK-1 (tandem of pore domain in a weak inwardly rectifying K+ channel (Twik)-related K+ channels); Hippocampus; Synaptic transmission; Synaptic plasticity; Cognitive impairment
资金
- NINDS NIH HHS [R56 NS097672, R01 NS062784, R01 NS116059, RO1NS062784, R56NS097972, P30 NS104177] Funding Source: Medline
TREK-1, a two-pore-domain K+ channel, is highly expressed in the central nervous system. Although aberrant expression of TREK-1 is implicated in cognitive impairment, the cellular and functional mechanism underlying this channelopathy is poorly understood. Here we examined TREK-1 contribution to neuronal morphology, excitability, synaptic plasticity, and cognitive function in mice deficient in TREK-1 expression. TREK-1 immunostaining signal mainly appeared in hippocampal pyramidal neurons, but not in astrocytes. TREK-1 gene knockout (TREK-1 KO) increases dendritic sprouting and the number of immature spines in hippocampal CA1 pyramidal neurons. Functionally, TREK-1 KO increases neuronal excitability and enhances excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). The increased EPSCs appear to be attributed to an increased release probability of presynaptic glutamate and functional expression of postsynaptic AMPA receptors. TREK-1 KO decreased the paired-pulse ratio and severely occluded the long-term potentiation (LTP) in the CA1 region. These altered synaptic transmission and plasticity are associated with recognition memory deficit in TREK-1 KO mice. Although astrocytic expression of TREK-1 has been reported in previous studies, TREK-1 KO does not alter astrocyte membrane K+ conductance or the syncytial network function in terms of syncytial isopotentiality. Altogether, TREK-1 KO profoundly affects the cellular structure and function of hippocampal pyramidal neurons. Thus, the impaired cognitive function in diseases associated with aberrant expression of TREK-1 should be attributed to the failure of this K+ channel in regulating neuronal morphology, excitability, synaptic transmission, and plasticity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据