Molecular re-engineering of excitation-inhibition balance in memory circuits

Abstract

Memory-regulating agents and methods that target actin binding LIM protein family, member 3 (ABLIM3).

What is claimed is: 
     
         1 . A method of identifying a candidate small molecule inhibitor of Ablim3, the method comprising:
 providing a test sample comprising a population of cells that express Ablim3;   contacting the sample with a test compound;   detecting subcellular localization of Ablim3 protein in the cells in the presence of the test compound;   determining whether the Ablim3 protein is localized to adherens junctions in the cells in the presence of the cells;   selecting as a candidate inhibitor a test compound that reduces localization of Ablim3 protein to adherens junctions.   
     
     
         2 . The method of  claim 1 , wherein the cells express an Ablim3 reporter construct, wherein Ablim3 is linked to a detectable label, preferably a fluorescent protein. 
     
     
         3 . The method of  claim 1 , further comprising evaluating actin cytoskeleton in the cells, and selecting as a candidate inhibitor a test compound that reduces localization of Ablim3 protein to adherens junctions and does not disrupt the actin cytoskeleton. 
     
     
         4 . The method of  claim 1 , further comprising:
 administering a candidate compound to an animal model;   evaluating an effect of the candidate compound on memory in the animal model; and   selecting a compound that improves memory in the animal model.   
     
     
         5 . The method of  claim 1 , wherein the compound improves pattern separation in the animal model. 
     
     
         6 . The method of  claim 1 , wherein the test compound is a polypeptide, polynucleotide, inorganic large or small molecule, or organic large or small molecule.