4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-17560-3

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Funding

  1. Canadian Institutes of Health Research (CIHR) [MOP119421, PJT-155959, PJT168922]
  2. Canadian Natural Science and Engineering Research Council [NSERC RGPIN 341498, RGPIN-2017-06295]

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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 behavioral arrests in the knockout mice. These results indicate that NLG2-mediated GABAergic transmission at the nRT-thalamic circuit represents a common mechanism underlying both epileptic seizures and ASD. Neuroligins are postsynaptic cell adhesion molecules that are involved in synapse function and autism spectrum disorder. The authors show that NLG2-mediated GABAergic transmission at the thalamic reticular nucleus-thalamic circuit is a common mechanism underlying epileptic seizures and ASD.

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