Dissociation of tic generation from tic expression during the sleep-wake cycle

Abstract

AbstractMotor tics, the hallmark of Tourette syndrome, are modulated by different behavioral and environmental factors. A major modulating factor is the sleep-wake cycle in which tics are attenuated to a large extent during sleep. This study demonstrates a similar reduction in tic expression during sleep in an animal model of chronic tic disorders and investigates the underlying neural mechanism. We recorded the neuronal activity during spontaneous sleep-wake cycles throughout continuous GABAA antagonist infusion into the striatum. Analysis of video streams and concurrent kinematic assessments indicated tic reduction during sleep in both frequency and intensity. Extracellular recordings in the striatum revealed a state dependent dissociation between motor tic expression and their macro-level neural correlates (“LFP spikes”) during the sleep-wake cycle. LFP spikes, which are highly correlated with tic expression during wakefulness, persisted during tic-free sleep and did not change their properties despite the reduced behavioral expression. Local, micro-level, activity near the infusion site was time-locked to the LFP spikes during wakefulness but this locking decreased significantly during sleep. These results suggest that while LFP spikes encode motor tic generation and feasibility, the behavioral expression of tics requires local striatal neural activity entrained to the LFP spikes, leading to the propagation of the activity to downstream targets and consequently their motor expression. These findings point to a possible mechanism for the modulation of tic expression in TS patients during sleep and potentially during other behavioral states.SummaryThe expression of motor tics, the defining symptom of Tourette syndrome, is modulated by environmental and behavioral factors. In this study, we explored tic modulation during the sleep-wake cycle and its underlying neurophysiological mechanism, using the rat model of chronic motor tic expression. Behaviorally, during sleep, tic frequency and intensity declined considerably. Physiologically, however, the macro-level neural correlates (termed “LFP spikes”) of tics persisted throughout the sleep-wake cycle, whereas the micro-level correlates were reduced during sleep. This dissociation between neuronal activity and its behavioral expression leads not only to a better understanding of tic modulation during sleep but may also suggest potential ways of affecting tic expression during natural behavior and when exposed to external modulating factors.HighlightsThe wake-sleep cycle modulates tic expression in chronically tic-expressing ratsSleep attenuates tics in the rats reminiscent of the phenomenon in TS PatientsDuring tic-less sleep tic generation persists via LFP spikesDuring sleep tic expression is blocked via striatal activity desynchronization