COMPOSITIONS AND METHODS FOR ENHANCING COGNITIVE FUNCTION AND SYNAPTIC PLASTICITY

摘要

The present invention provides compositions and methods for enhancing cognitive function and synaptic plasticity. According to the method, CaSUP++/SUP influx into excitatory neurons (nerve cells) is decreased by treatment with a number of different agents including divalent cations (e.g., MgSUP++/SUP), GABASUBB/SUB agonists, GABASUBA/SUB agonists, calcium channel blockers, and/or compounds that decrease action potential firing such as sodium channel blockers. Decreasing CaSUP++/SUP influx results in increased synaptic plasticity and enhanced cognitive function. In particular, decreasing CaSUP++/SUP influx associated with uncorrelated neural activity results in long-lasting increases in synaptic plasticity and cognitive function. This is achieved by administration of agents that cause a voltage-dependent block of NMDA receptors (e.g., divalent cations such as MgSUP++/SUP) or by administration of GABASUBB/SUB agonists such as baclofen. The invention further provides screening methods useful in identifying compounds that enhance synaptic plasticity and cognitive function.