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

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.

Subregion-specific rules govern the distribution of neuronal immediate-early gene induction

“…Based on our results, we propose several principles defining the distribution of IEG expression within neuronal assemblies. Consistent with previous observations, we find that the induction of IEGs within neuronal assemblies is graded (1,4), with substantial variation between cells (49)(50)(51)(52). It should be noted that IEGs vary in their basal expression levels (i.e., background levels), in their specificity of induction by experience (25), and in the level of induction they achieve (26,28,33,38).…”

“…S3). This dataset was used to calculate the mean expression of each IEG within each group of neurons expressing different numbers of IEGs (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Plotting the mean expression of each IEG (row) as a function of the number of coexpressed IEGs (column), demonstrated a strong correlation between the coherence of IEG expression and the expression levels of each IEG found within it ( Fig.…”

“…neurons | experience | inducible transcription | immediate-early genes | cell assemblies T he induction of activity-dependent transcription programs in the brain leads to long-lasting cellular adaptations necessary for the commitment of experiences to long-term memory (1)(2)(3)(4)(5)(6). The primary response to neuronal stimulation involves the induction of a set of immediate-early genes (IEGs), which predominantly encode early-response transcription factors (7)(8)(9)(10).…”

Acute social isolation alters neurogenomic state in songbird forebrain

“…S6). Thus, we suggest that increased CORT may well support aspects of the chamber response, perhaps as a permissive factor for altered gene expression (35), but alone is insufficient to account for all of the effects on gene expression that we observed. These experiments raise questions about how isolation is perceived: What sensations or sensory pathways contribute to awareness of whether a bird is alone or not?…”

“…EGR1, which showed the largest decrease after isolation (Fig. 1), has been extensively used as an indicator of neural activity associated with learning, memory, and perception of salience (35). In songbird research, the EGR1 ortholog is commonly .…”