Proceedings of The Physiological Society

Sleep Sleep and Circadian Rhythms (London, UK) (2018) Proc Physiol Soc 42, C28

Poster Communications

GABA and glutamate networks in the VTA regulate govern vigilance state

X. Yu1, W. Li2, Y. Ma1, K. Tossell1, J. J. Harris1,3, E. C. Harding1, W. Ba1, G. Miracca1, D. Wang2, L. Li2, J. Guo2, M. Chen4, Y. Li1, R. Yustos1, A. L. Vyssotski5, D. Burdakov3, Q. Yang2, H. Dong2, N. P. Franks1,6, W. Wisden1,6

1. Department of Life Sciences, Imperial College London, London, United Kingdom. 2. Department of Anesthesiology & Perioperative Medicine, Xijing Hospital, Xi'an, China. 3. The Francis Crick Institute, London, United Kingdom. 4. iHuman Institute, ShanghaiTech University, Shanghai, China. 5. Institute of Neuroinformatics, University of Zürich/ETH Zürich, Zürich, Switzerland. 6. Centre of Excellence in Neurotechnology and UK Dementia Research Institute, Imperial College London, London, United Kingdom.

We screened for novel circuits in the mouse brain that determine vigilance states. Using chemogenetic activation and EEG recordings, we converged on glutamatergic/nitrergic (NOS1) and GABAergic neurons in the VTA. Activating glutamatergic/NOS1 neurons, which were wake- and REM-sleep active, produced wakefulness via the nucleus accumbens and the lateral hypothalamus. Lesioning the glutamate cells impaired the consolidation of wakefulness, with many extra transitions to NREM sleep. In contrast, activation of GABAergic VTA neurons elicited a long-lasting NREM-like sleep akin to sedation. Lesioning them produced a large increase in wakefulness, which persisted for at least 4 months after lesioning. The VTA GABAergic neurons, however, are selectively wake- and REM sleep-active. Our findings suggest that VTAVgat neurons limit wakefulness by inhibiting the arousal-promoting VTA glutamatergic and/or dopamine neurons, as well as by projections to the lateral hypothalamus. Thus, the VTA, widely investigated for its contribution to goal- and reward-directed behaviors, contains circuitry with an unexpected role in regulating wakefulness.

Where applicable, experiments conform with Society ethical requirements