Genetic Mechanisms of Experience-Dependent Neuronal Plasticity

The brain has a remarkable ability to adapt its function in response to both environmental and internal cues. The cellular composition of the brain is largely static after birth; thus, persistent experience-dependent changes in brain function depend on altered programs of gene expression that result in the plasticity of circuit connectivity and network function. High-throughput sequencing studies have comprehensively cataloged stimulus-dependent programs of gene expression in the brain. The current challenge is to integrate this information in the context of specific cells and circuits to understand the mechanisms by which transcriptional regulation coordinates adaptive plasticity of the brain and behavior. Here, I review molecular genetics studies that reveal how neuronal activity-regulated gene products orchestrate intricate cellular and intercellular adaptations in response to changes in patterns of brain activity. I also discuss examples of genetic mutations that impair experience-dependent transcriptional plasticity in the context of neurodevelopmental disorders.