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尼古丁诱导的体外啮齿动物海马体θ频率振荡。

Nicotine induction of theta frequency oscillations in rodent hippocampus in vitro.

机构信息

Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.

出版信息

Neuroscience. 2010 Mar 10;166(1):84-93. doi: 10.1016/j.neuroscience.2009.11.072. Epub 2009 Dec 23.

Abstract

The hippocampus is an area important for learning and memory and exhibits prominent and behaviourally relevant theta (4-12 Hz) and gamma (30-100 Hz) frequency oscillations in vivo. Hippocampal slices produce similar types of oscillatory activity in response to bath-application of neurotransmitter receptor agonists. The medial septum diagonal band area (MS/DB) provides both a cholinergic and GABAergic projection to the hippocampus, and although it plays a major role in the generation and maintenance of the hippocampal theta rhythm in vivo, there is evidence for intrinsic theta generation mechanisms in the hippocampus, especially in area CA3. The aim of this study was to examine the role of the nicotinic receptor (nAChR) in the induction of oscillatory field activity in the in vitro preparation of the rat hippocampus. Bath-application of a low concentration of nicotine (1 muM) to transversely-cut hippocampal slices produced persistent theta-frequency oscillations in area CA3 of the hippocampus. These oscillations were reduced by both GABA(A) receptor antagonists and ionotropic glutamate receptor antagonists, indicating the involvement of local GABAergic and glutamatergic neurons in the production of the rhythmic theta activity. The nicotine-induced theta activity was inhibited by non-selective nAChR antagonists and partially by an alpha7* nAChR antagonist. The induction of theta frequency oscillations in CA3 by nicotine was mimicked alpha7* nAChR agonists but not by non-alpha7* nAChR agonists. In conclusion, theta activity in the hippocampus may be promoted by tonic stimulation of alpha7* nAChRs, possibly via selective stimulation of theta-preferring interneurons in the hippocampus that express post-synaptic alpha7* nAChRs.

摘要

海马体是学习和记忆的重要区域,在体内表现出突出的、与行为相关的θ(4-12 Hz)和γ(30-100 Hz)频率振荡。海马切片在应用神经递质受体激动剂的浴液中会产生类似类型的振荡活动。内侧隔核斜带区(MS/DB)向海马体提供胆碱能和 GABA 能投射,尽管它在体内海马体θ节律的产生和维持中起着主要作用,但海马体本身存在内在θ产生机制的证据,特别是在 CA3 区。本研究的目的是研究烟碱型乙酰胆碱受体(nAChR)在体外培养的大鼠海马体中诱导振荡场活动中的作用。低浓度尼古丁(1 μM)浴液应用于横向切割的海马切片,在海马体 CA3 区产生持续的θ频率振荡。这些振荡被 GABA(A)受体拮抗剂和离子型谷氨酸受体拮抗剂所减少,表明局部 GABA 能和谷氨酸能神经元参与了节律性θ活动的产生。非选择性 nAChR 拮抗剂和部分α7nAChR 拮抗剂抑制尼古丁诱导的θ活动。α7nAChR 激动剂模拟尼古丁诱导 CA3 中的θ频率振荡,但非α7nAChR 激动剂则不然。总之,海马体中的θ活动可能是由α7nAChR 的持续刺激促进的,可能是通过选择性刺激海马体中表达突触后α7*nAChR 的θ偏好中间神经元。

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