Inhibition of Cerebellar Dentate Nucleus-Zona Incerta Glutamatergic Circuit Improves Sleep Disturbances in Chronic Temporal Lobe Epilepsy Model.

BACKGROUND

Patients with chronic temporal lobe epilepsy (TLE) frequently experience various sleep disorders, characterized by reduced sleep duration, diminished sleep stages, and disrupted sleep patterns. Recent research has identified a population of GABAergic neurons in the ventral zona incerta (ZI) that is instrumental in promoting sleep, along with a neural pathway that connects the cerebellar dentate nucleus (CDN) to the ZI. However, the precise role of this circuit in regulating sleep patterns remains inadequately understood.

METHODS

This study employed anatomical, chemogenetic, optogenetic, and immunofluorescence staining techniques to investigate the potential of the CDN-ZI circuit in ameliorating sleep disturbances associated with TLE.

RESULTS

Our findings indicate that pilocarpine-treated mice exhibit significant sleep fragmentation and reduced sleep duration, particularly during non-rapid eye movement sleep. By employing optogenetic and chemogenetic methods to target CDN glutamatergic neurons, we observed a decrease in sleep fragmentation, an increase in overall sleep duration, and an enhancement in sleep quality in pilocarpine-treated mice. The inhibition of the CDN-ZI glutamatergic circuit through optogenetic and chemogenetic methods resulted in substantial improvements in sleep disturbances following TLE.

CONCLUSIONS

Targeting the CDN-ZI glutamatergic circuit represents a promising therapeutic strategy for addressing sleep disorders resulting from chronic TLE.