气候变化领域集成服务门户(CCPortal): Multiple cannabinoid signaling cascades powerfully suppress recurrent excitation in the hippocampus

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DOI	10.1073/pnas.2017590118
	Multiple cannabinoid signaling cascades powerfully suppress recurrent excitation in the hippocampus
	Jensen K.R.; Berthoux C.; Nasrallah K.; Castillo P.E.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	Recurrent excitatory neural networks are unstable. In the hippocampus, excitatory mossy cells (MCs) receive strong excitatory inputs from dentate granule cells (GCs) and project back onto the proximal dendrites of GCs. By targeting the ipsi- and contralateral dentate gyrus (DG) along the dorsoventral axis of the hippocampus, MCs form an extensive recurrent excitatory circuit (GC-MC-GC) whose dysregulation can promote epilepsy. We recently reported that a physiologically relevant pattern of MC activity induces a robust form of presynaptic long-term potentiation (LTP) of MC-GC transmission which enhances GC output. Left unchecked, this LTP may interfere with DG-dependent learning, like pattern separation—which relies on sparse GC firing—and may even facilitate epileptic activity. Intriguingly, MC axons display uniquely high expression levels of type-1 cannabinoid receptors (CB1Rs), but their role at MC-GC synapses is poorly understood. Using rodent hippocampal slices, we report that constitutively active CB1Rs, presumably via βγ subunits, selectively inhibited MC inputs onto GCs but not MC inputs onto inhibitory interneurons or CB1Rsensitive inhibitory inputs onto GCs. Tonic CB1R activity also inhibited LTP and GC output. Furthermore, brief endocannabinoid release from GCs dampened MC-GC LTP in two mechanistically distinct ways: during induction via βγ signaling and before induction via αi/o signaling in a form of presynaptic metaplasticity. Lastly, a single in vivo exposure to exogenous cannabinoids was sufficient to induce this presynaptic metaplasticity. By dampening excitatory transmission and plasticity, tonic and phasic CB1R activity at MC axon terminals may preserve the sparse nature of the DG and protect against runaway excitation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CB1R; Dentate gyrus; LTP; Metaplasticity; Presynaptic
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180880
作者单位	Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, United States; Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, United States
推荐引用方式 GB/T 7714	Jensen K.R.,Berthoux C.,Nasrallah K.,et al. Multiple cannabinoid signaling cascades powerfully suppress recurrent excitation in the hippocampus[J],2021,118(4).
APA	Jensen K.R.,Berthoux C.,Nasrallah K.,&Castillo P.E..(2021).Multiple cannabinoid signaling cascades powerfully suppress recurrent excitation in the hippocampus.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Jensen K.R.,et al."Multiple cannabinoid signaling cascades powerfully suppress recurrent excitation in the hippocampus".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).