Optimal functioning of the nervous system requires selective wiring of neural circuits, the precision of which is achieved through experience-dependent refinement after birth. A classic model system of experience- dependent neural development is ocular dominance plasticity in the visual system, where monocular visual deprivation in a critical period of early life shifts cortical responses. The investigators have recently discovered that normal binocular vision in the critical period drives the matching of orientation preference between the two eyes in the visual cortex, thus revealing a physiological purpose for critical period plasticity in normal development. The proposed experiments aim to study the synaptic and circuit mechanisms of the newly- discovered binocular matching process. First, single unit extracellular recording, in vivo whole cell recording, and computational analysi will be carried out to determine how visual cortical cells respond to binocular stimulation before the critical period and the role of synaptic inhibition in this binocular integration process. Second, chronic 2-photon calcium imaging will be performed to reveal how individual cortical cells change their monocular orientation tunings to match between the two eyes. Finally, the investigators will investigate the role of inhibition in the binocular matching process by studying the consequence of reducing inhibition, and by studying binocular response properties of subtypes of inhibitory interneurons. Together, these experiments will provide important data needed for a complete understanding of binocular matching. Because ocular dominance plasticity and its critical period is a model system for human amblyopia and strabismus, a full understanding of cortical changes that normally take place during development will have important implications for the understanding and treatment of these diseases.

Public Health Relevance

The long-term goal of our research is to reveal the function and development of precise connections between neurons in the nervous system. These studies are of great clinical importance, because many neurological and psychiatric disorders result from miswiring of synaptic connections during development, such as cortical blindness, seizure, and autism spectrum disorders. Our studies will thus contribute to the understanding and treatment of these diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY020950-05
Application #
8783096
Study Section
Special Emphasis Panel (ZRG1-IFCN-Q (02))
Program Officer
Steinmetz, Michael A
Project Start
2010-09-30
Project End
2018-06-30
Budget Start
2014-09-01
Budget End
2015-06-30
Support Year
5
Fiscal Year
2014
Total Cost
$427,981
Indirect Cost
$141,842
Name
Northwestern University at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
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