Identification of glutamatergic inputs to the sublaterodorsal tegmental nucleus and their role in REM sleep control

Rapid eye movement (REM) sleep is characterized by rapid eye movements, cortical activation, and paralysis of skeletal muscles. Sublaterodorsal tegmental nucleus (SLD) glutamate neurons play a critical role in generating REM sleep, and glutamate release in the SLD is needed to generate REM sleep. However, the source of glutamate inputs to SLD neurons remains poorly understood. Here, we characterized brain-wide glutamatergic inputs to the SLD using genetically-assisted tract tracing in mice and find input from the cortex and the brainstem (including in region surrounding the injection area, in the pons and the medulla). Because the vlPAG is a region known to regulate REM sleep, we wanted to characterize the activity of vlPAG→SLD glutamate neurons and did so using in vivo fiber photometry. We found that population activity of vlPAG glutamate neurons varied across the sleep-wake cycle. We also found that vlPAG glutamate neurons tended to increase their activity seconds before REM sleep onset and decreased their activity at REM sleep offset. However, more precise tools are needed to determine that vlPAG glutamate neurons function to gate the initiation and termination of REM sleep by controlling the activity of glutamate SLD neurons.