The goal of this proposal is to understand the cellular mechanisms of activity-dependent plasticity through molecular genetic studies of rat visual system development. We have previously cloned a large number of candidate plasticity-related genes (CPGs). Preliminary screening of these CPGs has identified six whose expression is modulated by light-driven neural activity in the visual cortex of the adult rat, and is also regulated during postnatal cortical development. In this proposal two of these CPGs, CPG2 and CPG15, will be used as molecular probes to test the following hypothesis: 1) CPG expression is regulated by physiological activity during rat visual system development. 2) CPGs regulated by physiological stimuli participate in activity- dependent developmental plasticity. To show that CPG2 and CPG15 developmental expression during the critical period for ocular dominance segregation. To further relate activity- dependent expression of CPG2 and CPG15 to critical period plasticity we will study how this expression is effected by monocular deprivation in rats where critical period plasticity is delayed by dark rearing. Based on sequence homologies, CPG2 and CPG15 have predictable cellular and subcellular distributions. To test these predictions, we propose to generate polyclonal antibodies against bacterially expressed CPG2 and CPG15. These antibodies will permit immunolocalization of the endogenous proteins. To test CPG2 and CPG15 participation in cellular events related to plasticity we will apply antisense oligonucleotides to primary neuronal cultures in order to abolish cellular expression of these proteins. As we expect CPG2 and CPG15 to be participating in synaptic restructuring associated with synaptic plasticity, the effects of antisense oligonucleotide application will be assayed by a morphological analysis of changes in dendritic structure and alterations in spine density.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29EY011894-02
Application #
2711220
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1997-07-01
Project End
1998-08-31
Budget Start
1998-07-01
Budget End
1998-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724