In the olfactory bulb, a cAMP/PKA/CREB-dependent form of learning occurs in the first week of life that provides a unique mammalian model for defining the epigenetic role of this evolutionarily ancient plasticity cascade. Odor preference learning in the week-old rat pup is rapidly induced by a 10-min pairing of odor and stroking. Memory is…

Gene transcription is a crucial step in the sequence of molecular, synaptic, cellular, and systems mechanisms underlying learning and memory. Here, we review the experimental evidence demonstrating that alterations in the levels and functionality of the methylated DNA-binding transcriptional regulator MeCP2 are implicated in the learning and…

Strong evidence supports a role for protein degradation in fear memory formation. However, these data have been largely done in only male animals. Here, we found that following contextual fear conditioning, females, but not males, had increased levels of proteasome activity and K48 polyubiquitin protein targeting in the dorsal hippocampus, the…

The spatial and temporal coordination of growth factor signaling is critical for both presynaptic and postsynaptic plasticity underlying long-term memory formation. We investigated the spatiotemporal dynamics of "Aplysia" cysteine-rich neurotrophic factor (ApCRNF) signaling during the induction of activity-dependent long-term…

O-GlcNAcylation of serine/threonine residues on target proteins occurs dynamically in postmitotic neurons of the hippocampus and may serve to control both the stability and activity of target proteins. Remarkably, the addition and removal of the O-GlcNAc posttranslational modifications are catalyzed by a pair of enzymes, the O-GlcNAc transferase…

The epigenome serves as a signal integration platform that encodes information from experience and environment that adds tremendous complexity to the regulation of transcription required for memory, beyond the directions encoded in the genome. To date, our understanding of how epigenetic mechanisms integrate information to regulate gene expression…

Storage of long-term memory requires not only protein synthesis but also protein degradation. In this article, we overview recent publications related to this issue, stressing that the balanced actions of protein synthesis and degradation are critical for long-term memory formation. We particularly focused on the brain-derived neurotrophic factor…

Behavioral flexibility is important in a changing environment. Previous research suggests that systems consolidation, a long-term poststorage process that alters memory traces, may reduce behavioral flexibility. However, exactly how systems consolidation affects flexibility is unknown. Here, we tested how systems consolidation affects: (1)…

Formation of long-term synaptic plasticity that underlies long-term memory requires new protein synthesis. Years of research has elucidated some of the transcriptional and translational mechanisms that contribute to the production of new proteins. Early research on transcription focused on the transcription factor cAMP-responsive element binding…

Using a hippocampus-dependent contextual threat learning and memory task, we report widespread, coordinated DNA methylation changes in CA1 hippocampus of Sprague-Dawley rats specific to threat learning at genes involved in synaptic transmission. Experience-dependent alternations in gene expression and DNA methylation were observed as early as 1 h…

Individual differences in cognitive decline during normal aging and Alzheimer's disease (AD) are common, but the molecular mechanisms underlying these distinct outcomes are not fully understood. We utilized a combination of genetic, molecular, and behavioral data from a mouse population designed to model human variation in cognitive outcomes to…

Multiple epigenetic mechanisms, including histone acetylation and nucleosome remodeling, are known to be involved in long-term memory formation. Enhancing histone acetylation by deleting histone deacetylases, like HDAC3, typically enhances long-term memory formation. In contrast, disrupting nucleosome remodeling by blocking the neuron-specific…

Long-term but not short-term memory and synaptic plasticity in many brain areas require neurotrophin signaling, transcription, and epigenetic mechanisms including DNA methylation. However, it has been difficult to relate these cellular mechanisms directly to behavior because of the immense complexity of the mammalian brain. To address that…

microRNAs (miRNAs) have emerged as potent regulators of learning, recent memory, and extinction. However, our understanding of miRNAs directly involved in regulating complex psychiatric conditions perpetuated by aberrant memory, such as in posttraumatic stress disorder (PTSD), remains limited. To begin to address the role of miRNAs in persistent…

Conditioned fear memories that are context-specific shortly after conditioning generalize over time. We exposed rats to a context reminder 30 d after conditioning, which served to reinstate context-specificity, and investigated how this reminder alters retrieval-induced activity in the hippocampus and anterior cingulate cortex (aCC) relative to a…