Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation

• Published in: Frontiers in Neuroanatomy Vol. 7; no. 7; p. 43
• Main Authors: ラザルス ミハエル, 裏出 良博, Zhang Jian-Ping, Xu Qi, Yuan Xiang-Shan, Cherasse Yoan, Schiffmann Serge N., de Kerchove d'Exaerde Alban, Qu Wei-Min, Urade Yoshihiro, Lazarus Michael, Huang Zhi-Li, Li Rui-Xi
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers research foundation 01.12.2013; Frontiers Research Foundation; Frontiers Media S.A
• Subjects: adeno-associated virus; Adenosine; Adenosine A2A receptors; Animals; Arousal; Axons; Brain; Brain stem; Caffeine; Cre-Lox; Diencephalon; Dorsal raphe nucleus; Forebrain; Green fluorescent protein; Hypothalamus (lateral); Immunohistochemistry; Mouse; Neurons; Neuroscience; Neurosciences; Nucleus Accumbens; Pallidum (ventral); Periaqueductal gray area; Preoptic area; Raphe nuclei; Sleep; Sleep and wakefulness; Substantia innominata; Ventral tegmentum; China; Japan; Cre-Lox; sleep; mouse; adeno-associated virus; nucleus accumbens; green fluorescent protein
• ISSN: 1662-5129; 1662-5129
• DOI: 10.3389/fnana.2013.00043

Adenosine A(2A) receptors (A(2A) Rs) in the nucleus accumbens (Acb) have been demonstrated to play an important role in the arousal effect of adenosine receptor antagonist caffeine, and may be involved in physiological sleep. To better understand the functions of these receptors in sleep, projections of A(2A)R neurons were mapped utilizing adeno-associated virus (AAV) encoding humanized Renilla green fluorescent protein (hrGFP) as a tracer for long axonal pathways. The Cre-dependent AAV was injected into the core (AcbC) and shell (AcbSh) of the Acb in A(2A)R-Cre mice. Immunohistochemistry was then used to visualize hrGFP highlighting the perikarya of the A(2A)R neurons in the injection sites, and their axons in projection regions. The data revealed that A(2A)R neurons exhibit medium-sized and either round or elliptic perikarya with their processes within the Acb. Moreover, the projections from the Acb distributed to nuclei in the forebrain, diencephalon, and brainstem. In the forebrain, A(2A) R neurons from all Acb sub-regions jointly projected to the ventral pallidum, the nucleus of the diagonal band, and the substantia innominata. Heavy projections from the AcbC and the ventral AcbSh, and weaker projections from the medial AcbSh, were observed in the lateral hypothalamus and lateral preoptic area. In the brainstem, the Acb projections were found in the ventral tegmental area, while AcbC and ventral AcbSh also projected to the median raphe nucleus, the dorsal raphe nucleus, and the ventrolateral periaqueductal gray. The results supply a solid base for understanding the roles of the A(2A)R and A(2A)R neurons in the Acb, especially in the regulation of sleep.