Circuit-level theories for sensory dysfunction in autism: convergence across mouse models

Frontiers in Neurology

Neurology

Han Chin Wang¹  Daniel E. Feldman²  Hannah R. Monday² 

[1] Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, United States;null;

关键词: autism;    sensory;    cortex;    theory;    excitability;    neural coding;    circuit;    inhibition;   

DOI  :  10.3389/fneur.2023.1254297

 received in 2023-07-06, accepted in 2023-08-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

Individuals with autism spectrum disorder (ASD) exhibit a diverse range of behavioral features and genetic backgrounds, but whether different genetic forms of autism involve convergent pathophysiology of brain function is unknown. Here, we analyze evidence for convergent deficits in neural circuit function across multiple transgenic mouse models of ASD. We focus on sensory areas of neocortex, where circuit differences may underlie atypical sensory processing, a central feature of autism. Many distinct circuit-level theories for ASD have been proposed, including increased excitation–inhibition (E–I) ratio and hyperexcitability, hypofunction of parvalbumin (PV) interneuron circuits, impaired homeostatic plasticity, degraded sensory coding, and others. We review these theories and assess the degree of convergence across ASD mouse models for each. Behaviorally, our analysis reveals that innate sensory detection behavior is heightened and sensory discrimination behavior is impaired across many ASD models. Neurophysiologically, PV hypofunction and increased E–I ratio are prevalent but only rarely generate hyperexcitability and excess spiking. Instead, sensory tuning and other aspects of neural coding are commonly degraded and may explain impaired discrimination behavior. Two distinct phenotypic clusters with opposing neural circuit signatures are evident across mouse models. Such clustering could suggest physiological subtypes of autism, which may facilitate the development of tailored therapeutic approaches.

【 授权许可】

Unknown   
Copyright © 2023 Monday, Wang and Feldman.