Despite the importance of visual experience in the normal and pathological development of the visual cortex, the molecular mechanisms by which visual activity induces long-lasting changes in the function of cortical synapses have not been defined. The highly modifiable synapses between excitatory neurons in the mammalian visual cortex use glutamate as a neurotransmitter. As the primary effectors of synaptic glutamate release, changes in the number and/or function of post-synaptic glutamate receptors (GluRs) are likely to dramatically effect synaptic strength. This proposal uses binocular and monocular deprivation paradigms to regulate the strength of synaptic connections in the rat visual cortex, and tests the hypothesis that an experience-induced increase in synaptic strength is mediated by delivery of GluRs, while a deprivation-induced decrease in synaptic strength is due to the removal of synaptic GluRs. Analysis of GluR levels is performed in synatoneurosomes, a subcellular fraction which is enriched for intact, metabolically active glutamatergic synapses. The power of this procedure is revealed by the observation that levels of synaptoneurosomal GluRs are highly correlated with changes in the physiological and pharmacological response properties of synaptic GluRs, and in fact are highly predictive of changes in synaptic strength. The role of synaptic protein synthesis in the long-term experience- dependent maintenance of synaptic GluR levels will also be examined in vivo, and in isolated metabolically active synaptic profiles in vitro. Bidirectional, activity-dependent control of synaptic GluR composition would represent a novel mechanism for the regulation of synaptic efficacy in the developing visual cortex, and identify potential targets (GluR or GluR trafficking proteins) for pharmacological intervention, especially in the case of severe, therapy-resistant amblyopia.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Small Research Grants (R03)
Project #
5R03EY013818-02
Application #
6620732
Study Section
Special Emphasis Panel (ZEY1-VSN (04))
Program Officer
Oberdorfer, Michael
Project Start
2002-02-01
Project End
2005-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
2
Fiscal Year
2003
Total Cost
$148,000
Indirect Cost
Name
University of Maryland College Park
Department
Biology
Type
Schools of Earth Sciences/Natur
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
He, Hai-Yan; Ray, Baisali; Dennis, Katie et al. (2007) Experience-dependent recovery of vision following chronic deprivation amblyopia. Nat Neurosci 10:1134-6
He, Hai-Yan; Hodos, William; Quinlan, Elizabeth M (2006) Visual deprivation reactivates rapid ocular dominance plasticity in adult visual cortex. J Neurosci 26:2951-5
Castellani, Gastone C; Quinlan, Elizabeth M; Bersani, Ferdinando et al. (2005) A model of bidirectional synaptic plasticity: from signaling network to channel conductance. Learn Mem 12:423-32
He, Hai-Yan; Rasmusson, Douglas D; Quinlan, Elizabeth M (2004) Progressive elevations in AMPA and GABAA receptor levels in deafferented somatosensory cortex. J Neurochem 90:1186-93