RT Journal Article SR Electronic T1 Arousal-state dependent alterations in VTA-GABAergic neuronal activity JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0356-19.2020 DO 10.1523/ENEURO.0356-19.2020 A1 Ada Eban-Rothschild A1 Jeremy C. Borniger A1 Gideon Rothschild A1 William J. Giardino A1 Joshua G. Morrow A1 Luis de Lecea YR 2020 UL http://www.eneuro.org/content/early/2020/02/10/ENEURO.0356-19.2020.abstract AB Decades of research have implicated the ventral tegmental area (VTA) in motivation, learning and reward processing. We and others recently demonstrated that it also serves as an important node in sleep/wake regulation. Specifically, VTA-dopaminergic neuron activation is sufficient to drive wakefulness and necessary for the maintenance of wakefulness. However, the role of VTA-GABAergic neurons in arousal regulation is not fully understood. It is still unclear whether VTA-GABAergic neurons predictably alter their activity across arousal states, what is the nature of interactions between VTA-GABAergic activity and cortical oscillations, and how activity in VTA-GABAergic neurons relates to VTA-dopaminergic neurons in the context of sleep/wake regulation. To address these, we simultaneously recorded population activity from VTA-subpopulations and EEG/EMG signals during spontaneous sleep/wake states and in the presence of salient stimuli in freely-behaving mice. We found that VTA-GABAergic neurons exhibit robust arousal-state-dependent alterations in population activity, with high activity and transients during wakefulness and REM sleep. During wakefulness, population activity of VTA-GABAergic neurons, but not VTA-dopaminergic neurons, was positively correlated with EEG gamma power and negatively correlated with theta power. During NREM sleep, population activity in both VTA-GABAergic and VTA-dopaminergic neurons negatively correlated with delta, theta, and sigma power bands. Salient stimuli, with both positive and negative valence, activated VTA-GABAergic neurons. Together, our data indicate that VTA-GABAergic neurons, like their dopaminergic counterparts, drastically alter their activity across sleep-wake states. Changes in their activity predicts cortical oscillatory patterns reflected in the EEG, which are distinct from EEG spectra associated with dopaminergic neural activity.Statement of Significance Little is known about how ventral tegmental area (VTA) neural ensembles couple arousal to motivated behaviors. Using cell-type specific genetic tools, we investigated the population activity of GABAergic and dopaminergic neurons within the VTA across sleep/wake states and in the presence of salient stimuli. We demonstrate that coordinated neural activity within VTA-GABAergic neurons peaks during wakefulness and REM sleep. Furthermore, neuronal activity in VTA-GABAergic neurons is correlated with high frequency, low amplitude cortical oscillations during waking, but negatively correlated with high amplitude slower frequency oscillations during NREM sleep. Our results demonstrate that VTA-GABAergic neuronal activity is tightly linked to cortical arousal and highlight this population as a potential important node in sleep/wake regulation.