Cell type specific inhibition of calretinin-positive neurons in the dorsomedial thalamus reduces arousal

01/30/2020

Anna Jász¹, Gergely Komlósi and László Acsády¹

¹ Institute of Experimental Medicine

Stress-related sleep disorders affect many people worldwide, however neuronal links between sleep and stress are presently unclear. Dorsomedial thalamus (DMT) can potentially connect these two phenomena since the involvement of DMT in stress and wakefulness is well established. The aim of our present research is to investigate the role of DMT in stress-related sleep disorders. Earlier experiments by our research group have shown that graded optogenetic stimulation of DMT calretinin positive cells (DMT/CR+) can generate arousal (Mátyás et al., 2018). Based on these results, we investigated the effect of photoinhibition of DMT/CR+ on normal sleep and on sleep following a stressful situation. Prolonged inhibition of DMT/CR+ at the beginning of the mice’ inactive phase led to a significant decrease in the EMG activity and movements of the mice and a concomitant increase in the power of sleep related delta activity in the EEG. Reduced arousal was maintained after terminating the inhibition. Prolonged inhibition of DMT/CR+ cells led to a 50% decrease in sleep onset. In the next step we used the same protocol following the exposure of mice to predator (fox) odor in a novel environment and studied the effect of poststress inhibition of DMT/CR+ cells on the development of stress induced sleep disturbances. Our experiments demonstrated that photoinhibition of the DMT/CR+ cells results in decreased vigilance, consistent with the proposal that these neurons are involved in the regulation of forebrain arousal level. The involvement of DMT/CR+ cells in altered, stress related elevation of arousal level remains to be established.