How visual information is processed and transformed in the nervous system is a fundamental question in vision research. Given its clear importance in visually-guided behaviors and the available genetic tools, the mouse superior colliculus (SC) holds great promise for understanding visual signal transformation and its mechanisms. The SC is a layered structure important for multimodal integration and sensorimotor transformation, and its superficial layers are purely visual and receive direct retinotopic inputs from the retina. In his proposal, the investigators will study the brain circuitry and synaptic mechanisms underlying the important transformations that take place in the retinocollicular pathway, especially the processing of motion direction. First, 2-photon calcium imaging will be performed to determine the direction selectivity of individual SC neurons and their spatial organization. These experiments will establish whether there is a depth-, region-, and/or cell type-specific organization of direction selectivity in the superficial SC, thereby forming a foundation for the following aims. Second, the investigators will determine the response properties of the retinal input that project to the SC. Genetically-encoded calcium indicators will be expressed in retinal ganglion cells and 2- photon imaging will be performed to visualize their axonal terminals in the colliculus. Third, the methods of imaging retinal terminals and collicular neurons will be used in a line of transgenic mice where retinocollicular projections are spatially altered, in order to determine whether direction selective retinal input is required for the direction selectivity in th SC. Finally, the investigator will perform in vivo whole cell recording to study visually-evoked responses in the SC. These experiments will be performed in transgenic mice where excitatory SC neurons can be silenced by optogenetic stimulation, thereby exposing the retinal input to the recorded cells. By comparing the selectivity of the total and retinal input to individual SC neurons, these experiments will start to reveal the synaptic mechanisms underlying the processing and transformation of direction selectivity in the retinocollicular pathway. Together, these experiments will generate important data needed for a complete understanding of visual processing in the brain. Because normal visual processing is compromised in a number of neurological and psychiatric disorders, such as dyslexia, schizophrenia and autism spectrum disorders, these studies will provide insights for the understanding and treatment of these disorders.

Public Health Relevance

A long-term goal of our research is to reveal the brain circuitry and synaptic mechanisms of visual signal processing and transformation. Because normal visual processing is compromised in a number of neurological and psychiatric disorders, such as dyslexia, schizophrenia and autism spectrum disorders, our studies will provide important insights for the understanding and treatment of these disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY026286-04
Application #
9613250
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Flanders, Martha C
Project Start
2015-12-01
Project End
2020-11-30
Budget Start
2018-12-01
Budget End
2020-11-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Virginia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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:
Liu, Pan; Thomson, Benjamin R; Khalatyan, Natalia et al. (2018) Selective permeability of mouse blood-aqueous barrier as determined by 15N-heavy isotope tracing and mass spectrometry. Proc Natl Acad Sci U S A 115:9032-9037
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
Feng, Liang; Puyang, Zhen; Chen, Hui et al. (2017) Overexpression of Brain-Derived Neurotrophic Factor Protects Large Retinal Ganglion Cells After Optic Nerve Crush in Mice. eNeuro 4:
Puyang, Zhen; Gong, Hai-Qing; He, Shi-Gang et al. (2017) Different functional susceptibilities of mouse retinal ganglion cell subtypes to optic nerve crush injury. Exp Eye Res 162:97-103
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
Feng, Liang; Chen, Hui; Yi, Ji et al. (2016) Long-Term Protection of Retinal Ganglion Cells and Visual Function by Brain-Derived Neurotrophic Factor in Mice With Ocular Hypertension. Invest Ophthalmol Vis Sci 57:3793-802
Yi, Ji; Puyang, Zhen; Feng, Liang et al. (2016) Optical Detection of Early Damage in Retinal Ganglion Cells in a Mouse Model of Partial Optic Nerve Crush Injury. Invest Ophthalmol Vis Sci 57:5665-5671

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