The role of the genome in experience-dependent plasticity: Extending the analogy of the genomic action potential

• Type of Material: Article
• Authors: David F. Clayton, Canadian Institute for Advanced Research; Ina Anreiter, Canadian Institute for Advanced Research; Maria Aristizabal, Canadian Institute for Advanced Research; Paul W. Frankland, Canadian Institute for Advanced Research; Elisabeth Binder, Emory University; Ami Citri, Canadian Institute for Advanced Research
• Language: English
• Date: 2020-09-22
• Publisher: NATL ACAD SCIENCES
• Publication Version: Final Published Version
• Copyright Statement: Published under the PNAS license
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1820837116
• Title of Journal or Parent Work: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• Volume: 117
• Issue: 38
• Start Page: 23252
• End Page: 23260
• Keywords: Science & Technology; plasticity; Science & Technology - Other Topics; MEMORY FORMATION; C-FOS; Multidisciplinary Sciences; SYNAPTIC PLASTICITY; genome; EPIGENETIC REGULATION; BDNF EXPRESSION; IMMEDIATE-EARLY GENE; GAG PROTEIN; DNA DEMETHYLATION; memory; TRANSGENERATIONAL INHERITANCE; MESSENGER-RNA
• Research Categories: Health Sciences, Human Development; Biology, Genetics

Abstract

Our past experiences shape our current and future behavior. These experiences must leave some enduring imprint on our brains, altering neural circuits that mediate behavior and contributing to our individual differences. As a framework for understanding how experiences might produce lasting changes in neural circuits, Clayton [D. F. Clayton, Neurobiol. Learn. Mem. 74, 185-216 (2000)] introduced the concept of the genomic action potential (gAP) - a structured genomic response in the brain to acute experience. Similar to the familiar electrophysiological action potential (eAP), the gAP also provides a means for integrating afferent patterns of activity but on a slower timescale and with longer-lasting effects. We revisit this concept in light of contemporary work on experience-dependent modification of neural circuits. We review the "Immediate Early Gene" (IEG) response, the starting point for understanding the gAP. We discuss evidence for its involvement in the encoding of experience to long-term memory across time and biological levels of organization ranging from individual cells to cell ensembles and whole organisms. We explore distinctions between memory encoding and homeostatic functions and consider the potential for perpetuation of the imprint of experience through epigenetic mechanisms. We describe a specific example of a gAP in humans linked to individual differences in the response to stress. Finally, we identify key objectives and new tools for continuing research in this area.