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基底前脑的动态胆碱能张力反映嗅觉行为中的奖赏寻求和强化。

Dynamic Cholinergic Tone in the Basal Forebrain Reflects Reward-Seeking and Reinforcement During Olfactory Behavior.

作者信息

Hanson Elizabeth, Brandel-Ankrapp Katie L, Arenkiel Benjamin R

机构信息

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States.

Postbaccalaureate Research Education Program, Baylor College of Medicine, Houston, TX, United States.

出版信息

Front Cell Neurosci. 2021 Feb 2;15:635837. doi: 10.3389/fncel.2021.635837. eCollection 2021.

Abstract

Sensory perception underlies how we internalize and interact with the external world. In order to adapt to changing circumstances and interpret signals in a variety of contexts, sensation needs to be reliable, but perception of sensory input needs to be flexible. An important mediator of this flexibility is top-down regulation from the cholinergic basal forebrain. Basal forebrain projection neurons serve as pacemakers and gatekeepers for downstream neural networks, modulating circuit activity across diverse neuronal populations. This top-down control is necessary for sensory cue detection, learning, and memory, and is disproportionately disrupted in neurodegenerative diseases associated with cognitive decline. Intriguingly, cholinergic signaling acts locally within the basal forebrain to sculpt the activity of basal forebrain output neurons. To determine how local cholinergic signaling impacts basal forebrain output pathways that participate in top-down regulation, we sought to define the dynamics of cholinergic signaling within the basal forebrain during motivated behavior and learning. Toward this, we utilized fiber photometry and the genetically encoded acetylcholine indicator GAChR2.0 to define temporal patterns of cholinergic signaling in the basal forebrain during olfactory-guided, motivated behaviors and learning. We show that cholinergic signaling reliably increased during reward seeking behaviors, but was strongly suppressed by reward delivery in a go/no-go olfactory-cued discrimination task. The observed transient reduction in cholinergic tone was mirrored by a suppression in basal forebrain GABAergic neuronal activity. Together, these findings suggest that cholinergic tone in the basal forebrain changes rapidly to reflect reward-seeking behavior and positive reinforcement and may impact downstream circuitry that modulates olfaction.

摘要

感觉知觉是我们如何内化外部世界并与之互动的基础。为了适应不断变化的环境并在各种情境中解读信号,感觉需要可靠,但对感觉输入的感知需要灵活。这种灵活性的一个重要调节因子是来自胆碱能基底前脑的自上而下的调节。基底前脑投射神经元充当下游神经网络的起搏器和守门人,调节不同神经元群体的回路活动。这种自上而下的控制对于感觉线索检测、学习和记忆是必要的,并且在与认知衰退相关的神经退行性疾病中受到不成比例的破坏。有趣的是,胆碱能信号在基底前脑内局部起作用,以塑造基底前脑输出神经元的活动。为了确定局部胆碱能信号如何影响参与自上而下调节的基底前脑输出通路,我们试图定义动机行为和学习过程中基底前脑内胆碱能信号的动态变化。为此,我们利用光纤光度法和基因编码的乙酰胆碱指示剂GAChR2.0来定义嗅觉引导的动机行为和学习过程中基底前脑胆碱能信号的时间模式。我们发现,在寻求奖励行为期间,胆碱能信号可靠地增加,但在一个“去/不去”嗅觉提示辨别任务中,奖励给予会强烈抑制胆碱能信号。观察到的胆碱能张力的短暂降低与基底前脑GABA能神经元活动的抑制相呼应。总之,这些发现表明,基底前脑的胆碱能张力迅速变化,以反映寻求奖励行为和正强化,并且可能影响调节嗅觉的下游回路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb11/7884767/3945b784978b/fncel-15-635837-g0001.jpg

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