Consolidation refers to time-dependent processes that convert labile forms of brain plasticity or memory into more permanent forms. This has been best described in the hippocampus, but similar processes occur in the developing visual cortex and may be essential for the maturation of visual circuits. Our goal is to identify the cellular mechanisms governing the consolidation of a classic model of experience-dependent cortical plasticity (ocular dominance plasticity (ODP). To achieve this goal we will use our established methods of triggering ODP in the visual cortex combined with behavioral state monitoring, intracortical infusion, optical imaging of intrinsic cortical signals, immunohistochemistry and single-neuron electrophysiology in vivo. These techniques are combined in a simple experimental design that allows us to examine the role of kinase, translational and post-transcriptional pathways that may be necessary for long-lasting modifications of cortical circuitry. We propose the following specific aims: 1. Determine the role of protein kinase A (PKA) in the consolidation of ODP. In this specific aim, we will test the hypothesis that PKA signaling is required for the consolidation of cortical plasticity. This will be accomplished by a) inhibiting PKA activity b) activating PKA activity and c) inhibiting PKA-AKAP binding in the visual cortex during the consolidation phase of ODP. 2. Determine the role of protein synthesis in the consolidation of ODP. In this specific aim, we will test the hypothesis that protein synthesis is required for the consolidation of cortical plasticity. This will be accomplished by reversibly inhibiting dendritic and global protein synthesis in the visual cortex during the consolidation phase of ODP. 3. Determine the role of transcriptional regulation in the consolidation of ODP. In this specific aim, we will test the hypothesis that chromatin modification is required for the consolidation of ODP. This will be accomplished by measuring changes in histone acetylation and by increasing or decreasing histone acetylation in the visual cortex during the consolidation phase of ODP.

Public Health Relevance

The research in this proposal will provide important new insights into how endogenous brain activation leads to long-lasting changes in cortical circuits. This will improve our understanding of normal and pathological brain development and memory formation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY019022-05
Application #
8302365
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Araj, Houmam H
Project Start
2008-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$336,798
Indirect Cost
$122,958
Name
University of Pennsylvania
Department
Neurosciences
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Frank, Marcos G; Cantera, Rafael (2014) Sleep, clocks, and synaptic plasticity. Trends Neurosci 37:491-501
Aton, Sara J; Broussard, Christopher; Dumoulin, Michelle et al. (2013) Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons. Proc Natl Acad Sci U S A 110:3101-6
Frank, Marcos Gabriel (2012) Erasing synapses in sleep: is it time to be SHY? Neural Plast 2012:264378
Aton, Sara J; Seibt, Julie; Dumoulin, Michelle et al. (2009) Mechanisms of sleep-dependent consolidation of cortical plasticity. Neuron 61:454-66