A common neuronal ensemble in nucleus accumbens regulates pain-like behaviour and sleep

Haiyan Sun, Zhilin Li, Zhentong Qiu, Yu Shen, Qingchen Guo, Su-Wan Hu, Hai-Lei Ding, Shuming An () and Jun-Li Cao ()
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Haiyan Sun: Xuzhou Medical University
Zhilin Li: Xuzhou Medical University
Zhentong Qiu: Xuzhou Medical University
Yu Shen: Xuzhou Medical University
Qingchen Guo: Xuzhou Medical University
Su-Wan Hu: Xuzhou Medical University
Hai-Lei Ding: Xuzhou Medical University
Shuming An: Xuzhou Medical University
Jun-Li Cao: Xuzhou Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract A comorbidity of chronic pain is sleep disturbance. Here, we identify a dual-functional ensemble that regulates both pain-like behaviour induced by chronic constrictive injury or complete Freund’s adjuvant, and sleep wakefulness, in the nucleus accumbens (NAc) in mice. Specifically, a select population of NAc neurons exhibits increased activity either upon nociceptive stimulation or during wakefulness. Experimental activation of the ensemble neurons exacerbates pain-like (nociceptive) responses and reduces NREM sleep, while inactivation of these neurons produces the opposite effects. Furthermore, NAc ensemble primarily consists of D1 neurons and projects divergently to the ventral tegmental area (VTA) and preoptic area (POA). Silencing an ensemble innervating VTA neurons selectively increases nociceptive responses without affecting sleep, whereas inhibiting ensemble-innervating POA neurons decreases NREM sleep without affecting nociception. These results suggest a common NAc ensemble that encodes chronic pain and controls sleep, and achieves the modality specificity through its divergent downstream circuit targets.

Date: 2023
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DOI: 10.1038/s41467-023-40450-3

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