Grant: Travel Awards - Institute Community Support

INTRODUCTION: Rapid eye movement (REM) sleep is characterized by cortical activation, muscle atonia and rapid eye movements. The neuronal circuitry that regulates REM sleep remains speculative; however, the sublaterodorsal tegmental nucleus (SLD) located in the brainstem is hypothesized to be important for controlling REM sleep. Previous findings suggest that gamma aminobutyric acid (GABA) releasing cells in the SLD (SLD-GABA) are active during REM sleep, and lesions of these neurons impair REM sleep expression suggesting its link to REM sleep regulation. Here, we used optogenetic to inhibit the activity of SLD-GABA neurons in order to identify their potential role in REM sleep control in mice. METHOD: Optogenetic is a technique used to manipulate the activity of neurons using light stimulation. This technique requires the expression of light sensitive membrane bound protein called opsins. In our study, we drove expression of inhibitory opsins (eArch3.0) in the SLD-GABA neurons using a viral vector driven genetic manipulation. Optic fibers were implanted above SLD for focal light delivery and electrodes were implanted to record brain and muscle activity for sleep-wake identification. RESULTS: Compared to the sham controls, we found that inhibition of SLD-GABA neurons during REM or non-REM (NREM) sleep promotes transition into wakefulness (n=5; unpaired t-test, p<0.001*** and p<0.001***, respectively.) Moreover, we demonstrated that 20s inhibition of SLD-GABA neurons promote longer period of wakefulness than 10s (two-way ANOVA RM, p<0.01*) suggesting that inhibition of SLD-GABA neurons also maintains wakefulness. CONCLUSIONS: Our findings show that inhibition of SLD-GABA neurons terminates sleep and promotes wakefulness. Our study will provide a deeper understanding of the REM sleep circuit and potentially make contributions in improving the therapeutic treatment for disorders linked to REM sleep dysregulation like REM sleep behavior disorder and narcolepsy.