Autism Spectrum Disorders (ASD) are a group of common neurodevelopmental disorders of diverse presentation, though sensory disturbances are consistently noted. Previous work has demonstrated a requirement for sensory input in the morphological maturation of subtypes of interneurons in the somatosensory cortex, but the effect this has on circuit activity and regional output is unknown. We hypothesize that sensory inputs recruit select interneuron subtypes to trigger the maturation of cortical circuits and that perturbations of this process cause lasting abnormalities in regional cortical output, which underlie the pathophysiology of neurodevelopmental disorders. To test our hypothesis, we will record the spontaneous network activity of subpopulations of neurons and in sensory deprived animals. We will identify the presynaptic inputs to these cells with an anatomical tracer. We will also utilize a mouse model of autism to reveal the function of a high-risk ASD gene in the maturation of circuits involving inhibitory interneurons and intracortical projection neurons. This investigation will fill a substantial gap in knowledge of ASD pathogenesis and the interaction between genetic background and activity-dependent developmental processes. The complete picture of ASD pathogenesis remains unclear. This project aims to describe how neuronal activity guides circuit development in the context of increased genetic risk, providing mechanistic insight into disease development and laying the groundwork for earlier diagnosis and novel treatment targets.

Public Health Relevance

Understanding and treating neurodevelopmental disorders of sensory perception requires a basic understanding of the development of circuits involved in somatosensation. With a mechanistic comprehension of the role of sensory input to different subyptes of cells and the synaptic receptors involved in intracortical coding of sensory stimuli, we can begin to understand the pathogenesis of disorders like Autism Spectrum Disorders, and develop improved treatments for the patients who suffer from sensory aberrations. ! !

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30MH117939-01A1
Application #
9612131
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Driscoll, Jamie
Project Start
2018-07-16
Project End
2022-07-15
Budget Start
2018-07-16
Budget End
2019-07-15
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Administration
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065