MOLECULAR RE-ENGINEERING OF EXCITATION-INHIBITION BALANCE IN MEMORY CIRCUITS
Memory-regulating agents and methods that target actin binding LIM protein family, member 3 (ABLIM3).
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.