Molecular and Cellular Basis of Learning Difficulties in Genetic Disorders

Abstract

Recent advances have revealed a plethora of genes, signalling pathways, cellular and circuit processes involved in learning and memory. Convergent evidence demonstrates that molecular mechanisms that regulate long‐lasting changes in synaptic function are critical for learning and memory. This evidence has had a key role in unraveling mechanisms responsible for learning disabilities. For example, mutations in the neurofibromatosis type I ( NF1 ) gene are a common genetic cause for learning disabilities. Studies in mice revealed that these learning deficits are caused by increases in Ras signalling leading to enhancements in synaptic inhibition and synaptic plasticity deficits. These deficits can be reversed by manipulations that target Ras signalling or inhibition. Current clinical trials are testing the efficacy of these treatments in NF1 . Studies in other genetic causes for learning disabilities have shown that it is possible to develop mechanism‐based treatments for these disorders in mice that are effective even when they are started in adulthood. Key Concepts: The molecular mechanisms that regulate long‐lasting changes in synaptic function are critical for learning and memory. Our growing understanding of mechanisms of memory has been effectively used to unravel the causes for memory deficits associated with animal models of several key genetic disorders, including NF1, tuberous sclerosis and fragile X. It is possible to develop mechanism‐based treatments for developmental disorders that are effective even when treatment is started in adulthood.