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Review
. 2022 Oct:141:104811.
doi: 10.1016/j.neubiorev.2022.104811. Epub 2022 Aug 9.

Epigenetic mechanisms regulate cue memory underlying discriminative behavior

Andrea Shang  1 , Kasia M Bieszczad  2
Affiliations
Review

Epigenetic mechanisms regulate cue memory underlying discriminative behavior

Andrea Shang et al. Neurosci Biobehav Rev. 2022 Oct.

Abstract

The burgeoning field of neuroepigenetics has introduced chromatin modification as an important interface between experience and brain function. For example, epigenetic mechanisms like histone acetylation and DNA methylation operate throughout a lifetime to powerfully regulate gene expression in the brain that is required for experiences to be transformed into long-term memories. This review highlights emerging evidence from sensory models of memory that converge on the premise that epigenetic regulation of activity-dependent transcription in the sensory brain facilitates highly precise memory recall. Chromatin modifications may be key for neurophysiological responses to transient sensory cue features experienced in the "here and now" to be recapitulated over the long term. We conclude that the function of epigenetic control of sensory system neuroplasticity is to regulate the amount and type of sensory information retained in long-term memories by regulating neural representations of behaviorally relevant cues that guide behavior. This is of broad importance in the neuroscience field because there are few circumstances in which behavioral acts are devoid of an initiating sensory experience.

Keywords: Behavior; Cue memory; DNA methylation; Epigenetics; Histone acetylation; Learning; Memory; Neurophysiology; Neuroplasticity; Neuroscience; Sensory systems.

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Figures

Fig. 1.
Fig. 1.. Experience elicits cue-dependent neurophysiological responses that can drive activity-dependent gene-expression gated by epigenetic mechanisms.
A simplified schematic in an auditory model shows the experiential effect of learning about an acoustic frequency cue on sound-elicited neurophysiological activity (highly activated vs. less highly activated vs. non-activated sensory cells; sp/s = spike rate). In cells highly responsive to the cue frequency (“BF cells”), activity-dependent gene expression is possible unless blocked by the presence of chromatin modifying enzymes (e.g., HDACs and DNMTs) that often work together to constrict chromatin conformation and repress transcription (A). If epigenetic repressors are removed naturally either by prior history (B) or by experimental manipulation (C), then cue-elicited activity in active BF cells (B) and even moderate activity in similarly tuned “nearby non-BF cells” (C) could sufficiently activate gene expression within those sensory cells to promote lasting changes that support the formation of cue-specific memory. The overarching message in this schematic is that the cue specificity of memory depends on whether cue responsive cells reach the threshold for de novo gene expression events. The hypothetical premise of this framework is two-fold: first, that gene expression within sensory cells activated by cues can initiate neuroplasticity events within sensory system circuits themselves that ultimately support the formation of cue-specific memory and behavior (e.g., top vs. middle row) including the degree of cue specificity in memory and behavior (e.g, middle vs. bottom row); and second, that all sensory systems participate broadly in memory system networks by contributing what cues and how much sensory detail is encoded in newly formed memories to underlie their sensory richness (c.f., Phan and Bieszczad, 2016).
Fig. 2.
Fig. 2.. Sensory systems are an initial part of the distributed network of memory.
Experience elicits lasting physiological changes in the sensory brain (c.f., Table 6) that are inherited to downstream brain regions. It is important to note that traditional associative regions (e.g., HPC, AMY) are dependent on initial processing of sensory cues within the sensory regions of the brain that have undergone an experience-dependent physiological change. While there is massive feedback to sensory systems from extra-sensory regions, these influences on memory function are likely secondary to sensory system mediated processes at the time of experience. Thus, a network of physiological changes across multiple sensory and non-sensory associative brain regions together constitutes the characteristics of memory that ultimately control behavior. Abbreviations: HPC – hippocampus, AMY – amygdala, NAc – nucleus accumbens, VTA – ventral tegmental area, PFC – prefrontal cortex, Cer – cerebellum, ERC – entorhinal cortex, IC – insular cortex.
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