Genes, plasticity and mental retardation

Abstract

Functional and structural plasticity is a fundamental property of the brain involved in diverse processes ranging from brain construction and repair to storage of experiences during lifetime. Our current understanding of different forms of brain plasticity mechanisms has advanced tremendously in the last decades, benefiting from studies of development and memory storage in adulthood and from investigations of diverse diseased conditions. In this review, we focus on the role of mental retardation (MR) genes and show how this developing area of research can enrich our knowledge of the cellular and molecular mechanisms of brain plasticity and cognitive functions, and of the dysfunctional mechanisms underlying MR. We describe two main groups of MR genes; those leading to dysfunctional neurodevelopmental programs and brain malformations, and those which rely on alterations in molecular mechanisms underlying synaptic organization and plasticity. We first explore the role of MR genes in key mechanisms of neurogenesis and neuronal migration during development and in the adult, such as actin and microtubule-cytoskeletal dynamics and signal transduction. We then define the contribution of MR genes to forms of activity-dependent synaptic modifications, such as those involved in molecular organization of the synapse, intracellular signaling regulating gene programs and neuronal cytoskeleton to control network remodeling. We trace the characteristics of MR genes playing key roles in many forms of brain plasticity mechanisms, and highlight specific MR genes that endorse distinct roles in different cell types or brain regions, and at various times of a brain lifetime.