0119 A DEDICATED BRAINSTEM CIRCUIT CONTROLS REM SLEEP

Abstract Introduction: It remains unclear which neural circuit triggers REM sleep and REM sleep atonia, but glutamate neurons in the subcoeruleus (SubCGLUT) are hypothesized to control REM sleep as well as REM sleep atonia by activating GABA neurons in the ventral medulla (vMGABA). Here, we aimed to determine how optogenetic activation and inhibition of the SubCGLUT-vMGABA circuit impact REM sleep and REM sleep atonia. Methods: To control the neuronal activity of the glutamatergic SubC neurons, we bilaterally infused 200nL of an adeno-associated viral vector (AAV) containing either a light-sensitive excitatory opsin (AAV-EF1α-DIO-ChETA-eYFP) or a light-sensitive inhibitory opsin (AAV- EF1α-DIO-ARCH-eYFP) or an inert control protein (AAV- EF1α-DIO-eYFP) into the SubC of 33 Vglut2-cre mice. Animals were instrumented for EEG and EMG recordings. SubCGLUT neurons were activated or silenced specifically during REM sleep. In another set of animals, the SubCGLUT-vMGABA circuit was inhibited continuously during REM sleep at the level of the vM. Only animals that had histological verification of eYFP expression in the SubC region and projection fibers in the vM were used for analysis. We used Vglut2 fluorescent in situ hybridization and/or Vglut2-tdTomato expressing mice to confirm the specificity of our virally-mediated opsin expression. Results: We found that activation of SubCGLUT neurons increased the length of REM sleep episodes by 77 ± 3% (n=5, p