Optogenetic Interrogation of Subpeduncular Tegmentum Reveals Roles in Sleep and Behavioral Arrest

In the developing mammalian neural tube, the V2a class of neurons is generated throughout the brainstem and spinal cord. Many studies have revealed that the primary function of these neurons is the patterning of motor behaviors such as breathing (Crone et al., 2012), reaching (Azim et al., 2014) and locomotion(Crone et al., 2009). In this report we show that optical stimulation of V2a neurons at the mid-hindbrain junction produces quantifiable changes in cortical oscillations. We find that brief (1min) stimulation of these neurons produces 3-7Hz oscillations in the prefrontal cortex (PFC) as well as behavioral arrest for the duration of stimulation. Similar slow oscillations in the medial PFC are known to correlate with freezing behavior (Karalis et al., 2016). Long term (8h) stimulation of the same V2a neurons promotes wakefulness that is sustained for days after stimulation. These experiments were performed in double transgenic mice (chx10 +/cre Rosa ChR2-GFP/+; p62-p106) expressing channelrhodopsin (ChR2) in V2a neurons with a sample size of 8 animals for each experiment. Littermate controls undergoing identical procedures and stimulation protocols but lacking ChR2 showed no cortical or behavioral response with optical stimulation at mid-hindbrain junction. This study is unique in its examination of cortical oscillations with optical stimulation of V2a at the mid-hindbrain junction. These findings suggest that V2a neurons at the mid-hindbrain junction can potentially mediate motor behaviors and wakefulness by modulating slow oscillations in the PFC.