Neuroscience Day

September 29, 2021

Large Scale Analysis of Cortical Sensory Processing Dysfunction in a Mouse Model of Autism

Mingyu Ye, PhD

Additional Authors: George Touloumes, Ganna Palagina, Kalemaki Aikaterini,Stelios Smirnakis

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social interaction, restricted or repetitive patterns of behaviors. Many researches have focused on the social deficit of ASD, less is known regarding abnormality in sensory processing. Indeed, ASD individuals often manifest atypical sensory behaviors, such as indifference to pain, hyper-/hypo- sensitive to specific sounds, light, or excessive smelling or touching of objects, etc. Multiple hypotheses have been put forward regarding cortical circuit malfunction in autism, including: abnormal reliability of sensory encoding, excitation to inhibition (E/I) imbalance, malfunctions in cortical column processing, and others. Nevertheless, a detailed mechanistic understanding of how cortical circuits malfunction during sensory processing in autism is largely demanded. Until recently it has not been possible to obtain a comprehensive picture of how cortical microcircuits function in their entirety. Here using MeCP2 duplication mouse model of autism and applying recently developed large scale two-photon imaging techniques( random access mesoscopic imaging), combining with mouse genetics, AAV virus, optogenetics and computational modeling, we aim to address two major questions in the field: How is sensory processing failed in MECP2 duplication syndrome over the course of disease progression? What is the underlying mechanisms causing this dysfunction?

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