Communication between the synapse and the nucleus in neuronal development, plasticity, and disease.
Sensory experience is critical for the proper development and plasticity of the brain throughout life. Successful adaptation to the environment is necessary for the survival of an organism, and this process requires the translation of specific sensory stimuli into changes in the structure and function of relevant neural circuits. Sensory-evoked activity drives synaptic input onto neurons within these behavioral circuits, initiating membrane depolarization and calcium influx into the cytoplasm. Calcium signaling triggers the molecular mechanisms underlying neuronal adaptation, including the activity-dependent transcriptional programs that drive the synthesis of the effector molecules required for long-term changes in neuronal function. Insight into the signaling pathways between the synapse and the nucleus that translate specific stimuli into altered patterns of connectivity within a circuit provides clues as to how activity-dependent programs of gene expression are coordinated and how disruptions in this process may contribute to disorders of cognitive function.
Cohen
Sonia
S
F.M. Kirby Neurobiology Center, Children's Hospital Boston and Departments of Neurology and Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. cohen@fas.harvard.edu
Greenberg
Michael E
ME
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003072:Cognition Disorders / Q000503:physiopathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D017362:Cyclic AMP Response Element-Binding Protein; D051783:Methyl-CpG-Binding Protein 2; D016760:Proto-Oncogene Proteins c-fos; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D002118:Calcium