Neuronal activity is important for development of eye-specific segregation and cortical cell orientation specificity in the mammalian visual system. The proposed studies will block or change retinal activity using pharmacological agents or immunotoxins in developing ferrets. Results will show effects of altered patterns of activity on the establishment and maintenance of neuronal connections, of changes in the connection patterns. The first set of experiments (Aim 1) will look quantitatively at the normal time course of segregation of afferents from the two eyes in the lateral geniculate nucleus (LGN), and will determine whether activity blockade during the period of initial segregation actually prevents segregation or causes desegregation or both. The second set of experiments (Aim 2) will determine the effects of removing the normal pattern retinal ganglion cell activity (synchronized bursts of action potentials in neighboring ganglion cells) on the development of receptive field properties in LGN and primary visual cortex. In the third set of experiments (Aim 3), the initial normal segregation of axons from the two eyes will be prevented by activity blockade from PND 1-10, and then the animals will be allowed a period of recovery, resulting in LGNs where the axons from the two eyes are completely segregated, but normal laminae do not form. The effects of this altered retinogeniculate projection on the physiology of single ceils and on functional organization in the primary visual cortex will be studied using electrophysiological recordings, optical imaging, and transneuronal labeling. This will help to determine whether normal lamination of eye-specific inputs in the LGN is necessary for normal visual function. The final series of experiments (Aims 4 and 5) will look at the effects on cortical cell receptive fields of removing ON-center activity during development. Results from these experiments will show how patterns of activity may be involved in developing receptive field properties. The proposed experiments should further our knowledge of the rules of activity-dependent development, and the consequences of disrupting connections; this may have implications for human developmental disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011369-09
Application #
7082049
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Oberdorfer, Michael
Project Start
1996-07-01
Project End
2009-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
9
Fiscal Year
2006
Total Cost
$283,056
Indirect Cost
Name
University of California Davis
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Failor, Samuel Wilson; Ng, Arash; Cheng, Hwai-Jong (2018) Monocular enucleation alters retinal waves in the surviving eye. Neural Dev 13:4
Failor, Samuel; Chapman, Barbara; Cheng, Hwai-Jong (2015) Retinal waves regulate afferent terminal targeting in the early visual pathway. Proc Natl Acad Sci U S A 112:E2957-66
Davis, Zachary W; Chapman, Barbara; Cheng, Hwai-Jong (2015) Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields. J Neurosci 35:14612-23
Davis, Zachary W; Sun, Chao; Derieg, Brittany et al. (2015) Epibatidine blocks eye-specific segregation in ferret dorsal lateral geniculate nucleus during stage III retinal waves. PLoS One 10:e0118783
Speer, Colenso M; Sun, Chao; Liets, Lauren C et al. (2014) Eye-specific retinogeniculate segregation proceeds normally following disruption of patterned spontaneous retinal activity. Neural Dev 9:25
Rubin, Carol M; van der List, Deborah A; Ballesteros, Jose M et al. (2011) Mouse mutants for the nicotinic acetylcholine receptor ß2 subunit display changes in cell adhesion and neurodegeneration response genes. PLoS One 6:e18626
Speer, Colenso M; Sun, Chao; Chapman, Barbara (2011) Activity-dependent disruption of intersublaminar spaces and ABAKAN expression does not impact functional on and off organization in the ferret retinogeniculate system. Neural Dev 6:7
Speer, Colenso M; Mikula, Shawn; Huberman, Andrew D et al. (2010) The developmental remodeling of eye-specific afferents in the ferret dorsal lateral geniculate nucleus. Anat Rec (Hoboken) 293:1-24
Huberman, Andrew D; Feller, Marla B; Chapman, Barbara (2008) Mechanisms underlying development of visual maps and receptive fields. Annu Rev Neurosci 31:479-509
Sun, Chao; Speer, Colenso M; Wang, Guo-Yong et al. (2008) Epibatidine application in vitro blocks retinal waves without silencing all retinal ganglion cell action potentials in developing retina of the mouse and ferret. J Neurophysiol 100:3253-63

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