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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013528-10
Application #
7796596
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Greenwell, Thomas
Project Start
2001-07-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
10
Fiscal Year
2010
Total Cost
$367,143
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Arroyo, David A; Feller, Marla B (2016) Spatiotemporal Features of Retinal Waves Instruct the Wiring of the Visual Circuitry. Front Neural Circuits 10:54
Bos, Rémi; Gainer, Christian; Feller, Marla B (2016) Role for Visual Experience in the Development of Direction-Selective Circuits. Curr Biol 26:1367-75
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 89:1317-1330
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
Morrie, Ryan D; Feller, Marla B (2016) Development of synaptic connectivity in the retinal direction selective circuit. Curr Opin Neurobiol 40:45-52
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
Morrie, Ryan D; Feller, Marla B (2015) An Asymmetric Increase in Inhibitory Synapse Number Underlies the Development of a Direction Selective Circuit in the Retina. J Neurosci 35:9281-6
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
Rosa, Juliana M; Bos, Rémi; Sack, Georgeann S et al. (2015) Neuron-glia signaling in developing retina mediated by neurotransmitter spillover. Elife 4:

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