Determining how neuronal connections become highly organized early in life is fundamental to understanding of how the nervous system develops. Precise patterns of neural connections emerge during development as inappropriate connections are eliminated, and appropriate ones are maintained. This competitive process is driven by neuronal activity such that cells that """"""""fire together, wire together."""""""" Connectivity in many parts of the developing visual system undergo restructuring through processes driven by action potential activity from the retina, even before the onset of vision. This proposal addresses the role of spontaneous periodic bursting activity in establishing functionally discrete projections from the retina to its central targets in the ferret. Specifically it focuses on how the innervation patterns of ON and OFF retinal ganglion cells are refined during development by mechanisms based on temporal differences in their spontaneous bursting patterns.
Specific aim 1 addresses what cellular interactions occur in the inner retina to create distinct spontaneous activity patterns of ON and OFF ganglion cells at appropriate periods in development. Interactions mediated by GABA and glutamate will be investigated using electrophysiological and calcium imaging techniques.
Specific aim 2 is to determine the temporal relationship between the bursting rhythms of ON and OFF cells, and investigate what information in their activity pattern could to segregation of their connectivity. Correlated activity between ON and OFF ganglion cells will be examined by recording extracellularly from pairs of cells. Modeling techniques will be used to test and predict how spontaneous patterns in ON and OFF ganglion cells can specify ON and OFF retinogeniculate connectivity.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010699-08
Application #
6518529
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
1994-07-01
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
8
Fiscal Year
2002
Total Cost
$311,115
Indirect Cost
Name
Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Bleckert, Adam; Zhang, Chi; Turner, Maxwell H et al. (2018) GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells. Proc Natl Acad Sci U S A 115:E12083-E12090
Gamlin, Clare R; Yu, Wan-Qing; Wong, Rachel O L et al. (2018) Assembly and maintenance of GABAergic and Glycinergic circuits in the mammalian nervous system. Neural Dev 13:12
Ge, Yuan; Kang, Yunhee; Cassidy, Robert M et al. (2018) Clptm1 Limits Forward Trafficking of GABAA Receptors to Scale Inhibitory Synaptic Strength. Neuron 97:596-610.e8
Zhang, Chi; Kolodkin, Alex L; Wong, Rachel O et al. (2017) Establishing Wiring Specificity in Visual System Circuits: From the Retina to the Brain. Annu Rev Neurosci 40:395-424
Gore, Bryan B; Miller, Samara M; Jo, Yong Sang et al. (2017) Roundabout receptor 2 maintains inhibitory control of the adult midbrain. Elife 6:
Sinha, Raunak; Hoon, Mrinalini; Baudin, Jacob et al. (2017) Cellular and Circuit Mechanisms Shaping the Perceptual Properties of the Primate Fovea. Cell 168:413-426.e12
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
Chozinski, Tyler J; Halpern, Aaron R; Okawa, Haruhisa et al. (2016) Expansion microscopy with conventional antibodies and fluorescent proteins. Nat Methods 13:485-8
Moore-Dotson, Johnnie M; Beckman, Jamie J; Mazade, Reece E et al. (2016) Early Retinal Neuronal Dysfunction in Diabetic Mice: Reduced Light-Evoked Inhibition Increases Rod Pathway Signaling. Invest Ophthalmol Vis Sci 57:1418-30
Hoon, Mrinalini; Sinha, Raunak; Okawa, Haruhisa et al. (2015) Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells. Proc Natl Acad Sci U S A 112:12840-5

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