Basal forebrain circuit for sleep-wake control

• Published in: Nature neuroscience Vol. 18; no. 11; pp. 1641 - 1647
• Main Authors: Xu, Min, Chung, Shinjae, Zhang, Siyu, Zhong, Peng, Ma, Chenyan, Chang, Wei-Cheng, Weissbourd, Brandon, Sakai, Noriaki, Luo, Liqun, Nishino, Seiji, Dan, Yang
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2015; Nature Publishing Group
• Subjects: 631/378/1385; 631/378/3920; 64/60; 9/74; Acetylcholine - metabolism; Animal Genetics and Genomics; Animals; Basal Forebrain - physiology; Behavioral Sciences; Biological Techniques; Biomedicine; Electroencephalography - methods; Experiments; GABAergic Neurons - metabolism; Mice; Nerve Net - physiology; Neurobiology; Neurons; Neurosciences; Parvalbumins - metabolism; Sleep; Sleep - physiology; Wakefulness - physiology; United States > US; California
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4143

The basal forebrain (BF) is important for sleep-wake control. In this study, the authors performed cell type–specific recording and manipulation of four genetically defined BF cell types in freely moving mice and mapped their synaptic connections in slices, providing a BF circuit diagram for sleep-wake control. The mammalian basal forebrain (BF) has important roles in controlling sleep and wakefulness, but the underlying neural circuit remains poorly understood. We examined the BF circuit by recording and optogenetically perturbing the activity of four genetically defined cell types across sleep-wake cycles and by comprehensively mapping their synaptic connections. Recordings from channelrhodopsin-2 (ChR2)-tagged neurons revealed that three BF cell types, cholinergic, glutamatergic and parvalbumin-positive (PV+) GABAergic neurons, were more active during wakefulness and rapid eye movement (REM) sleep (wake/REM active) than during non-REM (NREM) sleep, and activation of each cell type rapidly induced wakefulness. By contrast, activation of somatostatin-positive (SOM+) GABAergic neurons promoted NREM sleep, although only some of them were NREM active. Synaptically, the wake-promoting neurons were organized hierarchically by glutamatergic→cholinergic→PV+ neuron excitatory connections, and they all received inhibition from SOM+ neurons. Together, these findings reveal the basic organization of the BF circuit for sleep-wake control.