0039 Investigating the role of striatal dopamine in sleep and narcolepsy-cataplexy

Abstract Introduction Dopamine release in the striatum is known to govern reward, motor, and sleep behaviors. There also exists a link between pharmacological manipulation of dopamine receptors cataplexy occurrence, yet precise spatial temporal dynamics relation onset are not understood. In present study, we evaluate orexin knockout (OX KO) mice during physiological Methods OX KO were implanted with EEG/EMG electrodes, dLight1.1 was expressed nucleus accumbens core (NAcc), shell (NAcSh), dorsolateral (DLS) perform vivo fiber photometry freely-moving animals. NAcc NAcSh mice, ChrimsonR retrogradely ventral tegmental area (VTA), allow for optogenetic control midbrain projections different regions striatum. We wildtype (WT) as control. Three stimulation parameters used independent recordings: phasic 20 Hz stimulation, 10-40 variable tonic 2 stimulation. Results First, show that while response rewarding behaviors muted animals, there no difference across state transitions WT Second, demonstrate striking increase both NAcSh, but DLS, at cataplexy. This occurs independently animals engaged immediately prior cataplexy, suggesting characteristic all episodes. Finally, find high frequency did affect frequency, low reduced REM occurrence. Conclusion differences events, changes states, identify key node regulation, which helps further our understanding limbic circuitry underlies narcolepsy symptoms. Support (if any) University Michigan Gilmore Award Rackham Graduate Research Award.