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

ABSTRACT: Motor tics, the hallmark of Tourette syndrome (TS), 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 GABA_A 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. Local field potential (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 whereas 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 patients with TS during sleep and potentially during other behavioral states.

SUBMITTER: Vinner Harduf E

PROVIDER: S-EPMC8081921 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.

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

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