胆碱能的
神经科学
多巴胺
毒蕈碱乙酰胆碱受体
多巴胺受体D2
受体
多巴胺受体
化学
乙酰胆碱
多巴胺能
抑制性突触后电位
烟碱激动剂
作者
Eduardo F. Gallo,Julia E. Greenwald,Eric Teboul,Kelly M. Martyniuk,Yulong Li,Jonathan A. Javitch,Peter D. Balsam,Christoph Kellendonk
标识
DOI:10.1101/2020.09.07.284612
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 points to a role of the pause 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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