1. Dopamine D2 receptors modulate the cholinergic pause and inhibitory learning
- Author
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Joseph M. Villarin, Eric Teboul, Peter D. Balsam, Christoph Kellendonk, Jonathan A. Javitch, Julia E. Greenwald, Kelly M. Martyniuk, Eduardo F. Gallo, Yulong Li, and Jenna Yeisley
- Subjects
virus diseases ,Striatum ,Nucleus accumbens ,Biology ,Inhibitory postsynaptic potential ,female genital diseases and pregnancy complications ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Dopamine ,Dopamine receptor D2 ,medicine ,Cholinergic ,Premovement neuronal activity ,neoplasms ,Molecular Biology ,Neuroscience ,Acetylcholine ,medicine.drug - Abstract
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).
- Published
- 2021