Fundamental to understanding how neuronal circuits are created in cortex is defining the mechanisms by which electrical activity is transduced into structural changes in neurons and connections. Primary visual cortex (V1) has been a proving ground for describing the phenomena and mechanisms of activity- dependent plasticity during development. Within V1, ocular dominance plasticity, particularly during an early, well-defined critical period, is a model for understanding functional and structural changes initiated by visual activity. We propose to define the structural correlates of rapid functional plasticity during the critical period; in so doing, we seek to understand the mechanisms that sequentially transduce functional drive into structural changes in dendrites and axon terminals. In particular, spines are sites of the vast majority of excitatory synapses in cortex, and how their structure relates to functional plasticity in the intact cortex remains virtually unknown. We will use the techniques of intrinsic signal optical imaging, high resolution two-photon laser scanning microscopy in vivo and in vitro, and viral expression of exogenous proteins, in ferrets and mice, to examine: (1) the time course of functional changes in the ferret visual cortex during the critical period for ocular dominance plasticity; (2) the structural correlates of rapid functional changes in the ferret visual cortex; (3) structural changes in spines with varying synaptic drive in ferret visual cortex; (4) functional and structural changes in the mouse visual cortex following short- and long-term term visual deprivation, including changes in different layers and specific cell classes; (5) specific molecular mechanisms, including the roles of CaMKII, actin and the extracellular matrix, involved in translating functional changes to structural reorganization in the visual cortex. Together, these experiments will examine in unprecedented detail the extent and time course of structural changes at single synapses in the visual cortex, and reveal mechanisms underlying their dynamic regulation by vision. Such information is critical for explaining pathologies of cortical development, and for suggesting strategies for treatment. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017098-02
Application #
7163767
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Steinmetz, Michael A
Project Start
2006-01-01
Project End
2010-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2007
Total Cost
$400,538
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Miscellaneous
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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Mellios, Nikolaos; Sugihara, Hiroki; Castro, Jorge et al. (2011) miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity. Nat Neurosci 14:1240-2
Malik, Wasim Q; Schummers, James; Sur, Mriganka et al. (2011) Denoising two-photon calcium imaging data. PLoS One 6:e20490
Zheng, Henry W; Malik, Wasim Q; Runyan, Caroline A et al. (2011) Modeling two-photon calcium fluorescence of episodic V1 recordings using multifrequency analysis. Conf Proc IEEE Eng Med Biol Soc 2011:3016-9
Yu, Hongbo; Majewska, Ania K; Sur, Mriganka (2011) Rapid experience-dependent plasticity of synapse function and structure in ferret visual cortex in vivo. Proc Natl Acad Sci U S A 108:21235-40
Tropea, Daniela; Majewska, Ania K; Garcia, Rodrigo et al. (2010) Structural dynamics of synapses in vivo correlate with functional changes during experience-dependent plasticity in visual cortex. J Neurosci 30:11086-95
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