The present invention provides compositions and methods for enhancing cognitive function and synaptic plasticity. According to the method, Ca<SUP>++</SUP> influx into excitatory neurons (nerve cells) is decreased by treatment with a number of different agents including divalent cations (e.g., Mg<SUP>++</SUP>), GABA<SUB>B</SUB> agonists, GABA<SUB>A</SUB> agonists, calcium channel blockers, and/or compounds that decrease action potential firing such as sodium channel blockers. Decreasing Ca<SUP>++</SUP> influx results in increased synaptic plasticity and enhanced cognitive function. In particular, decreasing Ca<SUP>++</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 Mg<SUP>++</SUP>) or by administration of GABA<SUB>B</SUB> agonists such as baclofen. The invention further provides screening methods useful in identifying compounds that enhance synaptic plasticity and cognitive function.
COMPOSITIONS AND METHODS FOR ENHANCING COGNITIVE FUNCTION AND SYNAPTIC PLASTICITY