Autism spectrum disorder (ASD) is difficult to diagnose and treat because it is a heterogenous condition with diverse molecular and genetic etiologies. However, many models of ASD show a common disruption in the structural and functional connectivity between brain regions. This suggests the different etiologies of ASD may converge to impair the flow of neural activity through the brain, providing a shared mechanism that leads to behavioral changes.
To study how ASD disrupts the flow of neural activity through the brain, Tim Buschman and colleagues will combine mesoscale calcium imaging with a novel convolutional factorization algorithm1 to quantify the spatio-temporal dynamics of cortex-wide neural activity. Buschman and his team will use this approach to study the dynamics of neural activity in three different mouse models of ASD—a single gene mutation (Shank3), a copy number variation (deletion of the 16p11.2 locus) and a chemically induced model (valproic acid). This will identify what changes in neural dynamics are common in all three models and then relate these changes in neural activity to changes in behavior.
Once Buschman and his team understand how cortex-wide dynamics relate to behavioral phenotypes, they will use optogenetic spatio-temporally patterned stimulation to test whether rescuing disruptions in dynamics can rescue behavioral deficits. The long-term goal of this work is to provide a new understanding of how the flow of neural activity through the brain is disrupted in ASD, forming the foundation for new biomarkers and treatments for ASD.
- Identifying convergent cortical circuit impairments across multiple mouse models of autism
- Comparison of cortical circuit dysfunction in autism model mice
- Elucidating early disruptions of brain activity in mouse models of autism
- Role of autism risk genes in prefrontal circuits underlying social processing in mice
- Linking cortical circuit dysfunction and abnormal behavior in genetic mouse models of autism