Turning dreams on

Activation of GABAergic neurons in the ventral medulla can reliably induce REM sleep, the brain state associated with vivid dreaming.

HFSP Long-Term Fellow Franz Weber and colleagues
authored on Mon, 26 October 2015

Vivid dreams with typically highly emotional and illogical storylines occur during rapid eye movement (REM) sleep. The brain is highly active during REM sleep, probably making us dream, while skeletal muscles are paralyzed, thus preventing us from acting out our dreams. Earlier studies could localize the circuitry generating REM sleep within the brainstem. However, the detailed mechanisms and circuits controlling REM sleep remain poorly understood.

We found that activation of inhibitory (GABAergic) neurons in the ventral medulla induces REM sleep (Weber et al., 2015). To activate these neurons we specifically expressed the photo-sensitive ion channel channelrhodopsin in GABAergic neurons in mice. Then activating these neurons with blue laser light, while the mice were sleeping, reliably triggered REM sleep. Next, we wondered whether continuously stimulating GABAergic ventral medulla neurons during REM sleep might extend the duration of REM sleep periods. To address this question, we computed in real-time the brain state and only activated GABAergic ventral medulla neurons when the mouse spontaneously entered REM sleep and continued stimulating as long as the mouse stayed in REM sleep. Closed-loop stimulation of GABAergic ventral medulla neurons doubled the duration of REM sleep episodes. Hence, these neurons are not only involved in the induction of REM sleep, but are also important for the maintenance of this brain state. Finally, we also recorded the activity of identified GABAergic neurons in the ventral medulla, while the mice were naturally sleeping. All recorded neurons were most active during REM sleep supporting their role in inducing and maintaining REM sleep.

How do GABAergic neurons in the ventral medulla induce REM sleep?  REM sleep can only be entered from non-REM sleep. We found that activation of GABAergic neurons in a midbrain region, the ventrolateral periaqueductal gray, promotes NREM sleep. Interestingly, ventral medulla neurons innervate neurons in this region of the brain. Since GABAergic neurons are inhibitory, activation of GABAergic ventral medulla neurons during sleep should suppress non-REM promoting neurons in the ventrolateral periaqueductal gray. As a consequence, non-REM sleep is suppressed and the brain can switch from NREM into REM sleep.

In summary, our experiments revealed a key circuit within the brainstem that controls the induction and duration of REM sleep. The capability to turn on REM sleep on command might enable us to explore the still mysterious functions served by REM sleep and associated dreaming in future studies.

Reference

Control of REM Sleep by Ventral Medulla GABAergic Neurons. F. Weber, S. Chung, K.T. Beier, M. Xu, L. Luo and Y. Dan. Nature, 526, 435–438 (2015).

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