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

David F. Clayton*, Ina Anreiter, Maria Aristizabal, Paul W. Frankland, Elisabeth B. Binder, Ami Citri*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations


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.

Original languageAmerican English
Pages (from-to)23252-23260
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number38
StatePublished - 22 Sep 2020

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  • Genome
  • Memory
  • Plasticity


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