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 use a broad combination of techniques, including molecular biological, cell biological and electrophysiological techniques both in vitro and in vivo. We focus our experiments on maps of eye-preference and retinotopy in the superior colliculus of the mouse, which 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 superior colliculus, and activity dependent processes subsequently refine these sensory motor circuits to functional precision. We propose to examine the nature of activity that is necessary for the development of visual maps, and determine whether this activity is permissive or instructive in shaping circuit development. We also propose to examine the normal development of single retinal ganglion cell axon arbors in the superior colliculus of the mouse, and determine how disrupting retinal activity disrupts arbor development. We finally propose to investigate the synaptic mechanisms that mediate activity-dependent refinement of visual maps in the superior colliculus. 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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Central Visual Processing Study Section (CVP)
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Steinmetz, Michael A
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Yale University
Schools of Medicine
New Haven
United States
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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
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
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
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
Li, Hong; Fertuzinhos, Sofia; Mohns, Ethan et al. (2013) Laminar and columnar development of barrel cortex relies on thalamocortical neurotransmission. Neuron 79:970-86
Zhang, Jiayi; Ackman, James B; Xu, Hong-Ping et al. (2012) Visual map development depends on the temporal pattern of binocular activity in mice. Nat Neurosci 15:298-307
Dhande, Onkar S; Bhatt, Shivani; Anishchenko, Anastacia et al. (2012) Role of adenylate cyclase 1 in retinofugal map development. J Comp Neurol 520:1562-83

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