Autism spectrum disorders (ASDs) comprise a wide constellation of neurobehavioral conditions that arise from abnormal patterns of brain development. Several genetic and environmental factors predispose individuals to developing ASDs, each manifesting in certain core behaviors. The long-term goals of our research are to understand the relative contributions of these factors in producing the neural changes that underlie ASDs. The primary objective here is to characterize the alterations to cortical layer 5 projections in the CNTNAP2-/- mouse model of autism. The central hypothesis is that the aberrant migration of neurons to layer 5 in these mice results in enhanced sensorimotor activity from cortical layer 5 to the thalamus and motor centers. Several anatomical and behavioral features of autistic subjects have been identified, which forms the basis for the proposed investigation.
The specific aims of the project are to: 1) Determine the neuroanatomical connections of the ectopic neurons that have migrated improperly to layer 5 in the primary sensory cortical areas of CNTNAP2-/- mice and 2) Assess the synaptic properties and functional topography of the layer 5 projections to the thalamus in CNTNAP2-/- mice. This study will utilize a mouse model of the disease to examine the resultant pathological alterations to these forebrain components, which are predicted to account for aspects of the core behaviors associated with ASDs: abnormal social interactions, reduced vocal communication, and repetitive and restrictive behaviors. The proposed experiments are expected to clarify the roles of these and other forebrain components in ASDs and guide our future investigations aimed at directly linking these morphological alterations with autism and ultimately restoring normal behavior in this model system. These experiments will have a positive impact by illuminating the previously unappreciated role of the corticothalamic pathways in ASDs.

Public Health Relevance

This study is relevant to public health since it will broaden our knowledge and perspective of the role of the corticothalamic pathways in autism spectrum disorders and provide a foundation for the further exploration of abnormal sensory and motor processing in related neurological diseases. Therefore, this research is relevant to part of NIH's mission, since it develops the basic knowledge that will lead to improved methods for preventing and treating autism spectrum disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
1R03MH104851-01A1
Application #
8970178
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Panchision, David M
Project Start
2015-05-15
Project End
2017-04-30
Budget Start
2015-05-15
Budget End
2016-04-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Louisiana State University A&M Col Baton Rouge
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
075050765
City
Baton Rouge
State
LA
Country
United States
Zip Code
70803