Identification of glutamatergic inputs to the sublaterodorsal tegmental nucleus and their role in rapid eye movement 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 rapid eye movement sleep, and glutamate release in the sublaterodorsal tegmental nucleus is needed to generate rapid eye movement sleep. However, the source of glutamate inputs to sublaterodorsal tegmental nucleus neurons remains poorly understood. Here, we characterized brain-wide glutamatergic inputs to the sublaterodorsal tegmental nucleus 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 ventrolateral peri-aqueductal gray (vlPAG) is a region known to regulate rapid eye movement sleep, we wanted to characterize the activity of ventrolateral peri-aqueductal gray→sublaterodorsal tegmental nucleus glutamate neurons and did so using in vivo fiber photometry. We found that population activity of ventrolateral peri-aqueductal gray glutamate neurons varied across the sleep-wake cycle. We also found that ventrolateral peri-aqueductal gray glutamate neurons tended to increase their activity seconds before rapid eye movement sleep onset and decreased their activity at rapid eye movement sleep offset. However, more precise tools are needed to determine that ventrolateral peri-aqueductal gray glutamate neurons function to gate the initiation and termination of rapid eye movement sleep by controlling the activity of glutamate sublaterodorsal tegmental nucleus neurons.