Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system.
Sensory experience and the resulting synaptic activity within the brain are critical for the proper development of neural circuits. Experience-driven synaptic activity causes membrane depolarization and calcium influx into select neurons within a neural circuit, which in turn trigger a wide variety of cellular changes that alter the synaptic connectivity within the neural circuit. One way in which calcium influx leads to the remodeling of synapses made by neurons is through the activation of new gene transcription. Recent studies have identified many of the signaling pathways that link neuronal activity to transcription, revealing both the transcription factors that mediate this process and the neuronal activity-regulated genes. These studies indicate that neuronal activity regulates a complex program of gene expression involved in many aspects of neuronal development, including dendritic branching, synapse maturation, and synapse elimination. Genetic mutations in several key regulators of activity-dependent transcription give rise to neurological disorders in humans, suggesting that future studies of this gene expression program will likely provide insight into the mechanisms by which the disruption of proper synapse development can give rise to a variety of neurological disorders.
F.M. Kirby Neurobiology Center, Children's Hospital Boston, and Departments of Neurology and Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. Flavell@fas.harvard.edu
Steven W
SW
Flavell
Michael E
ME
Greenberg
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D013569:Synapses / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
D014157:Transcription Factors