Muscarinic cholinergic receptors modulate inhibitory synaptic rhythms in hippocampus and neocortex.
Muscarinic cholinergic receptors modulate inhibitory synaptic rhythms in hippocampus and neocortex.
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DOI：
10.3389/fnsyn.2014.00018
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发表时间：
2014
影响因子：
3.7
通讯作者：
Tang AH
中科院分区：
文献类型：
--
作者：
Alger BE;Nagode DA;Tang AH
乙酰胆碱(ACh)受体(MAChRs)的激活对神经元的许多特性以及许多认知行为都有重要影响。小的神经元回路构成了神经元和行为之间的中间组织水平，mAChRs影响组成这些回路的细胞之间的相互作用。电路活动通常通过细胞外记录局部场电位(LFP)来评估，LFP类似于体内脑电，由协调的神经元相互作用产生。与生理相关的电路活动的连贯形式表现为LFP中的节律振荡。与动物行为最密切相关的节律振荡的频率在4-80赫兹的范围内，这被细分为θ(4-14赫兹)、贝塔(15-29赫兹)和伽马(30-80赫兹)频段。MAChRs的激活触发了海马区和大脑皮层这些频段的节律性振荡。由GABA能中间神经元介导的抑制反应构成了这些振荡的一个显著特征，实际上，在许多情况下似乎是它们的主要潜在因素。一个重要的问题是，哪些中间神经元参与了节律的产生。除了直接影响细胞和网络特性外，mAChRs还可以引起内源性大麻素(内源性大麻素，ECB)的动员，通过作用于大脑的主要大麻素受体CB1R，调节包括GABA在内的某些神经递质的释放。CB1Rs只在部分中间神经元上大量表达，密度较低时在谷氨酸能神经元上大量表达。外源性大麻素通常会扰乱theta(θ)和Gamma(γ)范围的振荡，这可能有助于这些药物的行为效应。重要的是要了解mAChR驱动的ECB如何影响神经元电路活动，因为这些信息将提供更深入的了解ACh本身的行为，以及ECB和外源性大麻类化合物在动物行为中的影响。在介绍了mAChR系统的一些基本方面之后，本文将重点介绍有关在海马区和大脑皮层产生θ和γ节律的机制和回路的最新发现。强调了光遗传学方法探索ACh在节律产生中的多种作用的能力。
Activation of muscarinic acetylcholine (ACh) receptors (mAChRs) powerfully affects many neuronal properties as well as numerous cognitive behaviors. Small neuronal circuits constitute an intermediate level of organization between neurons and behaviors, and mAChRs affect interactions among cells that compose these circuits. Circuit activity is often assessed by extracellular recordings of the local field potentials (LFPs), which are analogous to in vivo EEGs, generated by coordinated neuronal interactions. Coherent forms of physiologically relevant circuit activity manifest themselves as rhythmic oscillations in the LFPs. Frequencies of rhythmic oscillations that are most closely associated with animal behavior are in the range of 4–80 Hz, which is subdivided into theta (4–14 Hz), beta (15–29 Hz) and gamma (30–80 Hz) bands. Activation of mAChRs triggers rhythmic oscillations in these bands in the hippocampus and neocortex. Inhibitory responses mediated by GABAergic interneurons constitute a prominent feature of these oscillations, and indeed, appear to be their major underlying factor in many cases. An important issue is which interneurons are involved in rhythm generation. Besides affecting cellular and network properties directly, mAChRs can cause the mobilization of endogenous cannabinoids (endocannabinoids, eCBs) that, by acting on the principal cannabinoid receptor of the brain, CB1R, regulate the release of certain neurotransmitters, including GABA. CB1Rs are heavily expressed on only a subset of interneurons and, at lower density, on glutamatergic neurons. Exogenous cannabinoids typically disrupt oscillations in the theta (θ) and gamma (γ) ranges, which probably contributes to the behavioral effects of these drugs. It is important to understand how neuronal circuit activity is affected by mAChR-driven eCBs, as this information will provide deeper insight into the actions of ACh itself, as well as into the effects of eCBs and exogenous cannabinoids in animal behavior. After covering some basic aspects of the mAChR system, this review will focus on recent findings concerning the mechanisms and circuitry that generate θ and γ rhythms in hippocampus and neocortex. The ability of optogenetic methods to probe the many roles of ACh in rhythm generation is highlighted.