Modulation of long-term potentiation in the hippocampus by pharmacological approach: A novel strategy for the development of cognitive enhancers

Learning and memory not only provide the foundations of cognition, but are also closely related to sensory and motor function. Neurodegenerative conditions such as Alzheimer’s disease and Parkinson’s disease are accompanied by deficits in synaptic function and cognition to varying degrees. The discovery of long-term potentiation (LTP) of hippocampal synaptic transmission, which has been recognized as a classical model of learning and memory at the cellular level, has spurred substantial progress in the development of cognitive enhancers in the past 20 years. Following intensive investigations into LTP, a variety of compounds and biologically active substances have been found to modulate hippocampal LTP via numerous molecular mechanisms including regulating presynaptic neurotransmitter release, postsynaptic N-methyl D-aspartate (NMDA) receptor activity, postsynaptic signal transduction and gene transcription. This review focuses on the progress of investigations into the overarching mechanisms of LTP, the drugs modulating LTP and prospects for the development of new drugs for treating cognitive impairments in the future.