Optical mini-stroke of thalamic networks impairs sleep stability, topography and cognition

Abstract

AbstractModelling stroke in animals remains a challenge for translational research, especially for the infraction of small subcortical arteries. Using combined fibre optics and photothrombosis technologies, we developed a novel model of optically-induced infarcts (Opto-STROKE). Combining our model with electrophysiological recordings in freely-behaving mice, we studied early and late consequent patho-physiological changes in the dynamics of sleep-wake circuits and cognitive performance. Here, focusing on inducing Opto-STROKE lesions in the intralaminar thalamus (IL), which in humans cause severe impairments of arousal, cognition, and affective symptoms, our model recapitulated important deficits on sleep disorders presented in humans including arousal instability, concurrent to an augmented slow-wave activity and a reduction gamma power bands during wakefulness. Moreover, during NREM sleep, spindle density was decreased and topographically shifted to frontal cortices when compared to control animals. Remarkably, gamma power and spindle density were correlated with decreased pain threshold and impaired prefrontal cortex-dependent working memory in Opto-STROKE mice relative to controls. Collectively, our combined method influences both anatomical and functional outcomes of the classical stroke procedures and offers new insights on the fundamental role of the media thalamus as a hub for the regulation of both sleep-wake architecture and cognition.