The mechanisms and function of spontaneous neural activity in the developing mammalian retina will be studied. Immature retinal neurons spontaneously generate correlated activity in the form of waves of action potentials that sweep across the retinal ganglion cell layer. These """"""""retinal waves"""""""" occur during the developmental period when retinal ganglion cell axons are segregating into eye-specific layers in the lateral geniculate nucleus. Experiments using a combination optical imaging, single cell electrophysiology, and multielectrode array recordings are proposed to investigate the mechanisms of inter-cellular coupling that underlie the generation of retinal waves. First, using knockout mice, we will identify the role of a particular gap junction coupled network in generating the correlation structure of spontaneous action potentials in retinal ganglion cells. Second, we will study the mechanisms underlying the ability of the neuromodulators adenosine and GABA to powerfully modulate network activity. One result of this work will be to determine general organizations principles responsible for generating the activity patterns required for driving activity-dependent developmental processes. This work should further our understanding of the organizing principles that govern the normal development of the human nervous system, making it possible to understand the origin of neurological birth defects and to devise strategies that allow the nervous system to regenerate functioning neural circuits after injury.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
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Greenwell, Thomas
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University of California Berkeley
Schools of Arts and Sciences
United States
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Morrie, Ryan D; Feller, Marla B (2016) Development of synaptic connectivity in the retinal direction selective circuit. Curr Opin Neurobiol 40:45-52
Arroyo, David A; Kirkby, Lowry A; Feller, Marla B (2016) Retinal Waves Modulate an Intraretinal Circuit of Intrinsically Photosensitive Retinal Ganglion Cells. J Neurosci 36:6892-905
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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
Dodani, Sheel C; Firl, Alana; Chan, Jefferson et al. (2014) Copper is an endogenous modulator of neural circuit spontaneous activity. Proc Natl Acad Sci U S A 111:16280-5

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