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Sleepless nights and social plights: medial septum GABAergic hyperactivity in a neuroligin 3–deficient autism model
Claire E. Cho, … , Dahee Jung, Reesha R. Patel
Claire E. Cho, … , Dahee Jung, Reesha R. Patel
Published October 1, 2024
Citation Information: J Clin Invest. 2024;134(19):e184795. https://doi.org/10.1172/JCI184795.
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Commentary

Sleepless nights and social plights: medial septum GABAergic hyperactivity in a neuroligin 3–deficient autism model

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Abstract

Social deficits represent a core symptom domain of autism spectrum disorder (ASD), which is often comorbid with sleep disturbances. In this issue of the JCI, Sun et al. explored a medial septum (MS) circuit linking these behaviors in a neuroligin 3 conditional knockout model of autism. They identified GABAergic neuron hyperactivity following neuroligin 3 deletion in the MS. This hyperactivity resulted in the inhibition of the downstream preoptic area (POA) and hippocampal CA2 region, resulting in sleep loss and social memory deficits, respectively. Inactivating the hyperactive MS GABA neurons or activating the POA or CA2 rescued the behavioral deficits. Together, these findings deepen our understanding of neural circuits underlying social and sleep deficits in ASD.

Authors

Claire E. Cho, Dahee Jung, Reesha R. Patel

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Figure 1

MSGABA neurons regulate social memory and sleep in Nlg3-cKO mice.

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MSGABA neurons regulate social memory and sleep in Nlg3-cKO mice.
Nlg3 k...
Nlg3 knockout induces hyperactivity of GABA neurons in the MS. Hyperactivated MSGABA neurons impair social memory by reducing CA2 activity and induces sleep loss by decreasing POA activity.

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