The brain organizes information about the sensory world into maps. Prominent examples are the maps of eye-preference and retinotopy in the lateral geniculate nucleus, superior colliculus and visual cortex. Experiments in this proposal will advance our understanding of mechanisms responsible for the development of precise neural circuitry in the mammalian brain. We will employ a broad range of techniques, including molecular biological, cell biological, neuroanatomical, electrophysiological and advanced optical imaging techniques in vitro and in vivo. We focus our experiments on maps of eye preference and retinotopy in the superior colliculus and lateral geniculate nucleus of the mouse. These structures are the dominant target of retinal projections to the brain. The lateral geniculate nucleus is the primary relay of visual information to the visual cortex, and the superior colliculu is a sensory motor structure that has emerged as an ideal model system for the examination of neural circuit development and function. It is widely hypothesized that molecular cues are responsible for the establishment of coarse map structure in the lateral geniculate and superior colliculus, and activity dependent processes subsequently refine these sensory motor circuits to functional precision. We first propose to definitively establish whether patterned spontaneous activity is necessary for the development of visual maps. We next propose to manipulate the temporal pattern of activity in the developing retina to examine the dependence of retinocollicular development of retinal ganglion cell activity. We finally propose to manipulate th spatial pattern of activity in the developing retina to examine the dependence of visual map development on the spatial character of spontaneous retinal activity. In all, the experiments in this proposal are designed to investigate the mechanisms responsible for the development of precise neural circuits in the mammalian brain, with a specific emphasis on the emergence of visual maps in the mouse superior colliculus.

Public Health Relevance

We are interested in understanding how complex brain circuits develop. We focus on the visual system, as its function is relatively well understood and it is especially important to human behavior. Our experiments have the potential to help develop techniques to restore visual function following eye trauma or disease, such as glaucoma or age related macular degeneration.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY015788-13
Application #
9452969
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Greenwell, Thomas
Project Start
2005-08-01
Project End
2019-12-31
Budget Start
2018-01-01
Budget End
2019-12-31
Support Year
13
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
Diao, Yupu; Cui, Liyuan; Chen, Yuqing et al. (2018) Reciprocal Connections Between Cortex and Thalamus Contribute to Retinal Axon Targeting to Dorsal Lateral Geniculate Nucleus. Cereb Cortex 28:1168-1182
Seabrook, Tania A; Burbridge, Timothy J; Crair, Michael C et al. (2017) Architecture, Function, and Assembly of the Mouse Visual System. Annu Rev Neurosci 40:499-538
Thompson, Andrew; Gribizis, Alexandra; Chen, Chinfei et al. (2017) Activity-dependent development of visual receptive fields. Curr Opin Neurobiol 42:136-143
Crair, Michael C; Mason, Carol A (2016) Reconnecting Eye to Brain. J Neurosci 36:10707-10722
Xu, Hong-Ping; Burbridge, Timothy J; Ye, Meijun et al. (2016) Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits. J Neurosci 36:3871-86
Xu, Hong-Ping; Burbridge, Timothy J; Chen, Ming-Gang et al. (2015) Spatial pattern of spontaneous retinal waves instructs retinotopic map refinement more than activity frequency. Dev Neurobiol 75:621-40
Ackman, James B; Crair, Michael C (2014) Role of emergent neural activity in visual map development. Curr Opin Neurobiol 24:166-75
Ribic, Adema; Liu, Xinran; Crair, Michael C et al. (2014) Structural organization and function of mouse photoreceptor ribbon synapses involve the immunoglobulin protein synaptic cell adhesion molecule 1. J Comp Neurol 522:900-20
Burbridge, Timothy J; Xu, Hong-Ping; Ackman, James B et al. (2014) Visual circuit development requires patterned activity mediated by retinal acetylcholine receptors. Neuron 84:1049-64
Furman, Moran; Xu, Hong-Ping; Crair, Michael C (2013) Competition driven by retinal waves promotes morphological and functional synaptic development of neurons in the superior colliculus. J Neurophysiol 110:1441-54

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