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 alters 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 cortical and thalamic mechanisms that underlie the binocular matching process.
In aim one, two-photon calcium imaging will be performed chronically to reveal how individual cortical cells change their monocular orientation tunings to match between the two eyes. In addition, two-photon imaging and electrophysiological recording will be used to characterize the binocular response properties of subtypes of inhibitory neurons before, during, and after the critical period.
In aim two, electrophysiological recordings will be conducted to determine whether there are more binocular neurons in the dorsal lateral geniculate nucleus (dLGN) of young mice than in adults, and whether these binocular dLGN neurons show significant matching in their orientation preference before V1. Additional experiments will be performed to determine whether the early matching in the dLGN is experience-dependent by recording from mice reared in complete darkness from birth. Finally, by combining cortical silencing and in vivo whole cell recording, the investigators will examine whether the binocular responses of dLGN input determine the binocular tuning of individual V1 neurons. Together, these experiments will reveal a novel link between the developmental plasticity at two successive stages of visual processing, and determine the role of visual thalamus in guiding binocular development in V1. Because ocular dominance plasticity and its critical period is a model for amblyopia and strabismus, a full understanding of cortical and subcortical changes that normally take place during development will have profound 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 amblyopia, strabismus, cortical blindness, and autism spectrum disorders. Our studies will contribute to the understanding and treatment of these diseases.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Greenwell, Thomas
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Virginia
Schools of Arts and Sciences
United States
Zip Code
Shi, Xuefeng; Jin, Yanjiao; Cang, Jianhua (2018) Transformation of Feature Selectivity From Membrane Potential to Spikes in the Mouse Superior Colliculus. Front Cell Neurosci 12:163
Barchini, Jad; Shi, Xuefeng; Chen, Hui et al. (2018) Bidirectional encoding of motion contrast in the mouse superior colliculus. Elife 7:
Cang, Jianhua; Savier, Elise; Barchini, Jad et al. (2018) Visual Function, Organization, and Development of the Mouse Superior Colliculus. Annu Rev Vis Sci 4:239-262
Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron et al. (2017) Retinal origin of direction selectivity in the superior colliculus. Nat Neurosci 20:550-558
Levine, Jared N; Chen, Hui; Gu, Yu et al. (2017) Environmental Enrichment Rescues Binocular Matching of Orientation Preference in the Mouse Visual Cortex. J Neurosci 37:5822-5833
Gu, Yu; Cang, Jianhua (2016) Binocular matching of thalamocortical and intracortical circuits in the mouse visual cortex. Elife 5:
Levine, Jared N; Gu, Yu; Cang, Jianhua (2015) Seeing Anew through Interneuron Transplantation. Neuron 86:858-860
Krishnan, Keerthi; Wang, Bor-Shuen; Lu, Jiangteng et al. (2015) MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex. Proc Natl Acad Sci U S A 112:E4782-91
Inayat, Samsoon; Barchini, Jad; Chen, Hui et al. (2015) Neurons in the most superficial lamina of the mouse superior colliculus are highly selective for stimulus direction. J Neurosci 35:7992-8003
Wang, Lupeng; Liu, Mingna; Segraves, Mark A et al. (2015) Visual Experience Is Required for the Development of Eye Movement Maps in the Mouse Superior Colliculus. J Neurosci 35:12281-6

Showing the most recent 10 out of 20 publications