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Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models.

Abstract：

:Autism spectrum disorder (ASD) is a continuum of neurodevelopmental disorders and needs new therapeutic approaches. Recently, oxytocin (OXT) showed potential as the first anti-ASD drug. Many reports have described the efficacy of intranasal OXT therapy to improve the core symptoms of patients with ASD; however, the underlying neurobiological mechanism remains unknown. The OXT/oxytocin receptor (OXTR) system, through the lateral septum (LS), contributes to social behavior, which is disrupted in ASD. Therefore, we selectively express hM3Dq in OXTR-expressing (OXTR+) neurons in the LS to investigate this effect in ASD mouse models developed by environmental and genetic cues. In mice that received valproic acid (environmental cue), we demonstrated successful recovery of impaired social memory with three-chamber test after OXTR+ neuron activation in the LS. Application of a similar strategy to Nl3R451C knock-in mice (genetic cue) also caused successful recovery of impaired social memory in single field test. OXTR+ neurons in the LS, which are activated by social stimuli, are projected to the CA1 region of the hippocampus. This study identified a candidate mechanism for improving core symptoms of ASD by artificial activation of DREADDs, as a simulation of OXT administration to activate OXTR+ neurons in the LS.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Horiai M,Otsuka A,Hidema S,Hiraoka Y,Hayashi R,Miyazaki S,Furuse T,Mizukami H,Teruyama R,Tamura M,Bito H,Maejima Y,Shimomura K,Nishimori K

doi

10.1038/s41598-020-79109-0

subject

Has Abstract

pub_date

2020-12-17 00:00:00

pages

22173

issue

1

issn

2045-2322

pii

10.1038/s41598-020-79109-0

journal_volume

10

pub_type

杂志文章

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