Direction-selective ganglion cells respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null direction, and are critical for driving ocular-motor reflexes that stabilize images on the retina as we move through a visual scene. The preferred direction of direction-selective ganglion cells cluster along the cardinal directions (up, down, left and right) and the direction-selective ganglion cells sensitive to each cardinal direction are organized into mosaics such that at each point in space, each direction of motion is represented. The predominant model for the generation of direction selectivity in the retina is that a particular class of interneurons forms inhibitory synapses on the null side of the dendritic tree of direction- selective ganglion cells. The mechanisms that instruct the emergence of mosaics comprised of cells that receive an asymmetric distribution of inhibitory inputs during development are unknown. Here we propose to use a combination of state-of-the-art electrophysiological and imaging techniques to determine the mechanisms that underlie the development of these two essential features of direction-selectivity - the circuits that underlie the null side inhibition and the existence of direction-selective ganglion cells mosaics. In particular, we will determine whether spontaneous retinal activity plays a critical role in the formation of these circuits.

Public Health Relevance

Our research goal is to determine the factors that instruct the development of visual responses in the mammalian retina. In particular, we are studying the circuits that underlie the ability of the retina to detect the direction of motion of an object in the visual scene. This direction-selectivity is critical for the normal visually-driven reflexes that stabilize an image on the retina as we move through a visual scene. Our work will determine what role neural activity in the retina plays in the wiring up of these direction-selective circuits. Developing a detailed understanding of the organizing principles that govern the normal development of the circuits may make it possible to understand the origin of neurological birth defects. Very early in the development, before visual experience is possible, both electrical and chemical activity is generated spontaneously throughout the immature visual system. There is growing evidence that this early activity is critical for the appropriate development of circuits that mediate vision. These findings give us insights as to why exposure of fetuses to pharmacological agents can lead to a variety of neuropathologies. In addition, gaining insights into the role of neural activity will provide critical insights into devising strategies that allow the nervous system to rewire normal functioning neural circuits in response to developmental abnormalities that affect vision.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01EY019498-06
Application #
8689040
Study Section
Biology and Diseases of the Posterior Eye (BDPE)
Program Officer
Greenwell, Thomas
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Morrie, Ryan D; Feller, Marla B (2016) Development of synaptic connectivity in the retinal direction selective circuit. Curr Opin Neurobiol 40:45-52
Rosa, Juliana M; Morrie, Ryan D; Baertsch, Hans C et al. (2016) Contributions of Rod and Cone Pathways to Retinal Direction Selectivity Through Development. J Neurosci 36:9683-95
Vlasits, Anna L; Morrie, Ryan D; Tran-Van-Minh, Alexandra et al. (2016) A Role for Synaptic Input Distribution in a Dendritic Computation of Motion Direction in the Retina. Neuron 89:1317-30
Firl, Alana; Ke, Jiang-Bin; Zhang, Lei et al. (2015) Elucidating the role of AII amacrine cells in glutamatergic retinal waves. J Neurosci 35:1675-86
Rosa, Juliana M; Bos, Rémi; Sack, Georgeann S et al. (2015) Neuron-glia signaling in developing retina mediated by neurotransmitter spillover. Elife 4:
Hamby, Aaron M; Rosa, Juliana M; Hsu, Ching-Hsiu et al. (2015) CaV3.2 KO mice have altered retinal waves but normal direction selectivity. Vis Neurosci 32:E003
Vlasits, Anna L; Bos, Rémi; Morrie, Ryan D et al. (2014) Visual stimulation switches the polarity of excitatory input to starburst amacrine cells. Neuron 83:1172-84
Triplett, Jason W; Wei, Wei; Gonzalez, Cristina et al. (2014) Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits. Neural Dev 9:2
Sun, Lu O; Jiang, Zheng; Rivlin-Etzion, Michal et al. (2013) On and off retinal circuit assembly by divergent molecular mechanisms. Science 342:1241974
Ford, Kevin J; Félix, Aude L; Feller, Marla B (2012) Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves. J Neurosci 32:850-63

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