Neuroligin 2 regulates absence seizures and behavioral arrests through GABAergic transmission within the thalamocortical circuitry.

ABSTRACT: Epilepsy and autism spectrum disorders (ASD) are two distinct brain disorders but have a high rate of co-occurrence, suggesting shared pathogenic mechanisms. Neuroligins are cell adhesion molecules important in synaptic function and ASD, but their role in epilepsy remains unknown. In this study, we show that Neuroligin 2 (NLG2) knockout mice exhibit abnormal spike and wave discharges (SWDs) and behavioral arrests characteristic of absence seizures. The anti-absence seizure drug ethosuximide blocks SWDs and rescues behavioral arrests and social memory impairment in the knockout mice. Restoring GABAergic transmission either by optogenetic activation of the thalamic reticular nucleus (nRT) presynaptic terminals or postsynaptic NLG2 expression in the thalamic neurons reduces the SWDs and behav

SUBMITTER: Cao F 

PROVIDER: S-EPMC7385104 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature