Autism Spectrum Disorder-like Behavior Caused by Reduced Excitatory Synaptic Transmission in Pyramidal Neurons of Mouse Prefrontal Cortex

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Oct 13

PMID 33046712

Citations 59

Authors

Hiroaki Sacai

Kazuto Sakoori

Kohtarou Konno

Kenichiro Nagahama

Honoka Suzuki

Takaki Watanabe

Masahiko Watanabe

Naofumi Uesaka

Masanobu Kano

Affiliations

Soon will be listed here.

Abstract

Autism spectrum disorder (ASD) is thought to result from deviation from normal development of neural circuits and synaptic function. Many genes with mutation in ASD patients have been identified. Here we report that two molecules associated with ASD susceptibility, contactin associated protein-like 2 (CNTNAP2) and Abelson helper integration site-1 (AHI1), are required for synaptic function and ASD-related behavior in mice. Knockdown of CNTNAP2 or AHI1 in layer 2/3 pyramidal neurons of the developing mouse prefrontal cortex (PFC) reduced excitatory synaptic transmission, impaired social interaction and induced mild vocalization abnormality. Although the causes of reduced excitatory transmission were different, pharmacological enhancement of AMPA receptor function effectively restored impaired social behavior in both CNTNAP2- and AHI1-knockdown mice. We conclude that reduced excitatory synaptic transmission in layer 2/3 pyramidal neurons of the PFC leads to impaired social interaction and mild vocalization abnormality in mice.

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