PT  - JOURNAL ARTICLE
AU  - Eduardo F. Gallo
AU  - Julia Greenwald
AU  - Eric Teboul
AU  - Kelly M. Martyniuk
AU  - Yulong Li
AU  - Jonathan A. Javitch
AU  - Peter D. Balsam
AU  - Christoph Kellendonk
TI  - Dopamine D2 receptors modulate the cholinergic pause and inhibitory learning
AID  - 10.1101/2020.09.07.284612
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.07.284612
4099  - http://biorxiv.org/content/early/2020/09/07/2020.09.07.284612.short
4100  - http://biorxiv.org/content/early/2020/09/07/2020.09.07.284612.full
AB  - 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).Competing Interest StatementThe authors have declared no competing interest.