Neuropsychiatric disorders with developmental origins affect more than 15% of children in the United States and poses a major public health concern requiring $35 billion a year to address in large part due to secondary disability. Clinical efforts to diagnose, treat, and monitor disease have been hindered because they rely on observations of non-specific clusters of symptoms, thus limiting current pharmacologic therapeutics to symptom management. Initial studies report that distal cortical areas fail to connect in these disorders, however, the development of more effective pharmacological interventions requires a better basic understanding of normal maturation and implicated pathophysiology. These processes can be examined in mice. Such work in our lab has identified a necessary driver of maturation?Lynx1? for a projection commonly impaired from the frontal cortex to the visual cortex that mediates visual attention processing. This proposal seeks to more fully examine how Lynx1 promotes normal neural development in this key cortical connection and will investigate the functional and structural consequences of aberrant development in the absence of this important molecule. I hypothesize that Lynx1, an endogenous nicotinic receptor inhibitor, regulates the integration of this projection into forming neural networks that enact visual attention. This pathophysiological insight will promote the development of more effective diagnosis and targeted therapies for neurodevelopmental disorders.

Public Health Relevance

Neurodevelopmental disorders are prevalent in the United States, yet efficacious treatments are lacking and tools for diagnosis are limited. This proposal seeks to identify maturation mechanisms guiding long-range cortical connectivity involved in these disorders through functional and structural studies in mice. This pathophysiological insight will promote the development of more effective diagnosis and targeted therapies for neurodevelopmental disorders.

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 #
5F30MH111143-02
Application #
9350170
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Driscoll, Jamie
Project Start
2016-09-01
Project End
2020-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029