Plasticity of the adult visual cortex plays an important role in normal processes of perceptual learning as well as in functional recovery following central nervous system lesions. We propose in particular that the normal integrative processes seen in visual cortex are recruited for adaptive changes following CNS lesions. To understand the mechanisms underlying adult cortical plasticity, as well as its perceptual consequences, we will work with an experimental model involving the reorganization of cortical topography following binocular retinal lesions. We have made a computational model that relates the normal properties of visual cortical neurons to the changes occurring after retinal lesions, and further relates these changes to perceptual fill-in. In the current study we propose to test the predictions of this model, and to quantify the nature of the functional changes in V1 that ensue following retinal lesions. Monitoring the functional reorganization will be done by electrophysiological recordings in awake behaving monkeys, allowing us to follow the process of reorganization over multiple time points and over large areas of cortex. These experiments are also intended to resolve controversies concerning the prevalence, extent and nature of the remapping of cortical topography in the lesion model. To address issues of mechanism, we will explore the involvement of different components of cortical circuitry in the reorganization. This will be done by in vivo 2-photon imaging of cells, dendrites and axons labeled by neuronal infection with genetically engineered AAV virus carrying genes encoding different fluorophores. We will investigate the relative contribution of long-range horizontal connections, feedback connections from higher order cortical areas, and interlaminar connections within V1, as well as changes in dendritic morphology. With these experiments we hope to learn about the central mechanisms of recovery following retinal degenerations, such as macular degeneration and other forms of CNS damage. Our approach is also designed to further our understanding of the perceptual consequences of the cortical changes induced by retinal damage. Beyond their value in the study of lesion dependent plasticity, these studies will be of relevance to understanding the mechanism of normal experience dependent changes in the visual pathway, such as those associated with perceptual learning. The proposed experiments will help reveal the mechanisms of functional recovery following lesions and degenerative diseases of the CNS, including adult macular degeneration. The studies will also be relevant to understanding the normal experience dependent changes associated with perceptual learning, since the same circuits are likely to be involved.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY018119-05
Application #
8212127
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Steinmetz, Michael A
Project Start
2008-02-01
Project End
2013-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
5
Fiscal Year
2012
Total Cost
$401,544
Indirect Cost
$163,944
Name
Rockefeller University
Department
Biology
Type
Other Domestic Higher Education
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065
Marik, Sally A; Yamahachi, Homare; Meyer zum Alten Borgloh, Stephan et al. (2014) Large-scale axonal reorganization of inhibitory neurons following retinal lesions. J Neurosci 34:1625-32
Marik, Sally A; Olsen, Olav; Tessier-Lavigne, Marc et al. (2013) Death receptor 6 regulates adult experience-dependent cortical plasticity. J Neurosci 33:14998-5003
Chen, Jiabin; Yamahachi, Homare; Gilbert, Charles D (2010) Experience-dependent gene expression in adult visual cortex. Cereb Cortex 20:650-60
Marik, Sally A; Yamahachi, Homare; McManus, Justin N J et al. (2010) Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex. PLoS Biol 8:e1000395
Yamahachi, Homare; Marik, Sally A; McManus, Justin N J et al. (2009) Rapid axonal sprouting and pruning accompany functional reorganization in primary visual cortex. Neuron 64:719-29