How information is routed to the neocortex as a function of behavioral state is a fundamental but poorly understood question in modern neuroscience. The thalamic reticular nucleus (TRN) is an inhibitory structure that is hypothesized to gate information throughput from thalamus to cortex, but experimental evidence clarifying the details of this process is lacking. To overcome these limitations, interrogate intac TRN microcircuits and understand their role in behavior we will create novel molecular tools that confer genetic targeting specificity to this brain structure Aim I. Using innovative genome editing technologies, we will maximize targeting success, while minimizing the time taken to validate these tools. Using these tools, we will ask how TRN microcircuits are functionally organized addressing how the thalamus may differentially gate multiple competing inputs to guide behavioral output, Aim II. In addition to opening several venues for further basic understanding of brain microcircuits, state regulation and cognition, this research will be of tremendous translational impact. In a parallel collaboration between Halassa and Feng, we are studying a mouse model of monogenic human autism with a primary TRN dysfunction. The genetic methods we are creating will equip us with the ability to develop molecular and optical interventional tools for treatment of this disorder and other neurodevelopmental diseases.

Public Health Relevance

This project will develop new transgenic mouse lines for Cre-recombinase specific expression in the thalamic reticular nucleus (TRN). The thalamic reticular nucleus is a critical but poorly understood structure in the mammalian forebrain, involved in regulating sleep and attentional states. The mice will be used to answer physiological questions in addition to serving a springboard for translational studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH105779-02
Application #
9062515
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
Beckel-Mitchener, Andrea C
Project Start
2015-05-15
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016