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大鼠前额叶皮层第2/3层锥体细胞中代谢型胆碱能调制诱导的非尖峰平台电位和持续放电

Non-apical plateau potentials and persistent firing induced by metabotropic cholinergic modulation in layer 2/3 pyramidal cells in the rat prefrontal cortex.

作者信息

Hagger-Vaughan Nicholas, Kolnier Daniel, Storm Johan F

机构信息

Brain Signalling Laboratory, Section for Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

出版信息

PLoS One. 2024 Dec 10;19(12):e0314652. doi: 10.1371/journal.pone.0314652. eCollection 2024.

DOI:10.1371/journal.pone.0314652
PMID:39656720
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11630621/
Abstract

Here we describe a type of depolarising plateau potentials (PPs; sustained depolarisations outlasting the stimuli) in layer 2/3 pyramidal cells (L2/3PC) in rat prefrontal cortex (PFC) slices, using whole-cell somatic recordings. To our knowledge, this PP type has not been described before. In particular, unlike previously described plateau potentials that originate in the large apical dendrite of L5 cortical pyramidal neurons, these L2/3PC PPs are generated independently of the apical dendrite. Thus, surprisingly, these PPs persisted when the apical dendrite was cut off (~50 μm from the soma), and were sustained by local calcium application only to the somatic and basal dendritic compartments. The prefrontal L2/3PCs have been postulated to have a key role in consciousness, according to the Global Neuronal Workspace Theory: their long-range cortico-cortical connections provide the architecture required for the "global work-space", "ignition", amplification, and sustained, reverberant activity, considered essential for conscious access. The PPs in L2/3PCs caused sustained spiking that profoundly altered the input-output relationships of these neurons, resembling the sustained activity suggested to underlie working memory and the mechanism underlying "behavioural time scale synaptic plasticity" in hippocampal pyramidal cells. The non-apical L2/3 PPs depended on metabotropic cholinergic (mAChR) or glutamatergic (mGluR) modulation, which is probably essential also for conscious brain states and experience, in both wakefulness and dreaming. Pharmacological tests indicated that the non-apical L2/3 PPs depend on transient receptor potential (TRP) cation channels, both TRPC4 and TRPC5, and require external calcium (Ca2+) and internal Ca2+ stores, but not voltage-gated Ca2+ channels, unlike Ca2+-dependent PPs in other cortical pyramidal neurons. These L2/3 non-apical plateau potentials may be involved in prefrontal functions, such as access consciousness, working memory, and executive functions such as planning, decision-making, and outcome prediction.

摘要

在此,我们利用全细胞膜片钳记录技术,描述了大鼠前额叶皮层(PFC)切片中第2/3层锥体神经元(L2/3PC)的一种去极化平台电位(PPs;持续去极化,持续时间超过刺激时间)。据我们所知,这种PP类型此前尚未被描述过。特别地,与先前描述的起源于第5层皮层锥体神经元大顶树突的平台电位不同,这些L2/3PC的PPs独立于顶树突产生。因此,令人惊讶的是,当顶树突被切断(距胞体约50μm)时,这些PPs仍然持续存在,并且仅通过向胞体和基底树突部分局部施加钙来维持。根据全局神经元工作空间理论,前额叶L2/3PC被认为在意识中起关键作用:它们的长程皮质-皮质连接提供了“全局工作空间”、“点火”、放大以及持续的、回荡性活动所需的结构,这些活动被认为是意识通达所必需的。L2/3PC中的PPs引起持续放电,深刻改变了这些神经元的输入-输出关系,类似于被认为是工作记忆基础的持续活动以及海马锥体细胞中“行为时间尺度突触可塑性”的潜在机制。非顶树突L2/3的PPs依赖于代谢型胆碱能(mAChR)或谷氨酸能(mGluR)调制,这在清醒和做梦状态下对于有意识的脑状态和体验可能也至关重要。药理学测试表明,非顶树突L2/3的PPs依赖于瞬时受体电位(TRP)阳离子通道,即TRPC4和TRPC5,并且需要外部钙(Ca2+)和内部钙库,但不像其他皮质锥体神经元中的钙依赖性PPs那样依赖电压门控钙通道。这些L2/3非顶树突平台电位可能参与前额叶功能,如通达意识、工作记忆以及执行功能,如计划、决策和结果预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f73c/11630621/59ca2b8028b6/pone.0314652.g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f73c/11630621/e4e2ff43d954/pone.0314652.g002.jpg
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