The molecular and cellular biology of enhanced cognition

Although there is considerable evidence for animals and people with cognitive enhancements, mechanistic studies of enhanced cognition are comparatively rare.Genetic manipulations of more than 30 different genes have been shown to enhance learning and memory (L&M) in mutant mice. These 'smart' mice provide powerful tools to investigate the cellular and molecular mechanisms underlying L&M enhancements.Strikingly, long-term potentiation (LTP) is enhanced in most of the mutant mice with enhanced L&M, providing a compelling argument for a role of LTP-like mechanisms in L&M.It is possible to enhance synaptic plasticity and L&M by manipulating various neuronal signalling molecules, ranging from membrane receptors to nuclear transcription factors. Interestingly, N-methyl-D-aspartate (NMDA) receptor signalling and subsequent cyclic-AMP response-element-binding protein (CREB)-dependent transcription are upregulated in many mutant mice with enhanced L&M.Targeting the molecular mechanisms that are associated with L&M enhancements may lead to the development of general therapies for cognitive disorders, and could represent a novel strategy to address the extraordinary complexity of the genetic and environmental factors responsible for the myriad of cognitive disorders that affect a surprisingly large percentage of the population.