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Interagency Autism Coordinating Committee (IACC)
Autism Research Database
Office of Autism Research Coordination (OARC)
 
Project Element Element Description

Project Title

Project Title

Disrupted Network Activity in Neonatal Cortex of Mouse Models of Autism

Principal Investigator

Principal Investigator

Crair, Michael

Description

Description

The etiology of autism is complex and mysterious. Autism has a strong genetic basis but there is remarkable diversity and heterogeneity in genes that are associated with the disorder. Despite this heterogeneity, a convergence of evidence suggests that disruptions in synapse function, neuronal activity and circuit formation are the origin of behaviors associated with autism. Michael C. Crair and his colleagues aim to test the hypothesis that abnormal neuronal activity in the newborn brain leads to the emergence of abnormal functional connectivity that is the root cause of autism. This model reasons that genetic disruptions associated with autism produce profound alterations in ongoing activity in the early developing brain, potentially before overt behavioral symptoms are observed. This altered early brain activity causes neural circuit wiring defects through errors in Hebb-like mechanisms — changes in synaptic connections as a result of their mutual correlated activity, leading to the formation of memories or learned behavior — or related activity-dependent mechanisms. In this model, Crair and his group hypothesize that the diversity in genes associated with autism produce the heterogeneity of symptoms due to the spectrum of deficits in early neuronal activity that affect the wiring of neurons and circuits in the developing brain. The researchers employ in vivo techniques to optically image neuronal activity using genetically encoded calcium indicators across the entire neonatal mouse cortex. Ongoing spontaneous neuronal activity in the newborn mouse cortex is highly dynamic, but is repetitive and changes predictably with development. Preliminary experiments indicate that this activity, imaged live and noninvasively in an unanesthetized and mobile animal, is altered in mouse models of autism. These experiments are directly testing the hypothesis that disruptions in the neonatal brain produce neural circuit wiring defects that lead to autism-associated behaviors.

Funder

Funder

Simons Foundation

Fiscal Year Funding

Fiscal Year Funding

125000

Current Award Period

Current Award Period

2014-2016

Strategic Plan Question

Strategic Plan Question

Question 2: How Can I Understand What Is Happening?

Strategic Plan Objective

Strategic Plan Objective

Green dot: Objective has greater than or equal to the recommended funding. 2SB. Launch three studies that specifically focus on the neurodevelopment of females with ASD, spanning basic to clinical research on sex differences by 2011. IACC Recommended Budget: $8,900,000 over 5 years.

Project Link

Project Link

Disrupted Network Activity in Neonatal Cortex of Mouse Models of Autism (External web link)

Institution

Institution

Yale University

State/Country

State/Country

Connecticut

Project Number

Project Number

308450

Federal or Private?

Federal or Private?

Private

Received ARRA Funding?

Received ARRA Funding?

No

History/Related Projects

History/Related Projects

Disrupted Network Activity in Neonatal Cortex of Mouse Models of Autism | 62500 | 2014 | 308450

 
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