Dopamine D2 receptors modulate the cholinergic pause and inhibitory learning

被引：0
作者：
Eduardo F. Gallo
Julia Greenwald
Jenna Yeisley
Eric Teboul
Kelly M. Martyniuk
Joseph M. Villarin
Yulong Li
Jonathan A. Javitch
Peter D. Balsam
Christoph Kellendonk
机构：
[1] Fordham University,Department of Biological Sciences
[2] Columbia University,Department of Psychiatry
[3] New York State Psychiatric Institute,Division of Molecular Therapeutics
[4] Columbia University,Department of Neuroscience
[5] Peking University School of Life Sciences,State Key Laboratory of Membrane Biology
[6] Columbia University,Department of Molecular Pharmacology and Therapeutics
[7] Columbia University,Department of Psychology
[8] New York State Psychiatric Institute,Division of Developmental Neuroscience
来源：
Molecular Psychiatry | 2022年 / 27卷
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摘要：
Cholinergic interneurons (CINs) in the striatum respond to salient stimuli with a multiphasic response, including a pause, in neuronal activity. Slice-physiology experiments have shown the importance of dopamine D2 receptors (D2Rs) in regulating CIN pausing, yet the behavioral significance of the CIN pause and its regulation by dopamine in vivo is still unclear. Here, we show that D2R upregulation in CINs of the nucleus accumbens (NAc) lengthens the pause in CIN activity ex vivo and enlarges a stimulus-evoked decrease in acetylcholine (ACh) levels during behavior. This enhanced dip in ACh levels is associated with a selective deficit in the learning to inhibit responding in a Go/No-Go task. Our data demonstrate, therefore, the importance of CIN D2Rs in modulating the CIN response induced by salient stimuli and point to a role of this response in inhibitory learning. This work has important implications for brain disorders with altered striatal dopamine and ACh function, including schizophrenia and attention-deficit hyperactivity disorder (ADHD).
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页码：1502 / 1514
页数：12
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