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Experience-dependent epigenomic reorganization in the hippocampus.

ABSTRACT: 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 following memory acquisition and became more pronounced after 24 h. Gene ontology analysis revealed significant enrichment of functional categories related to synaptic transmission in genes that were hypomethylated at 24 h following threat learning. Integration of these data sets with previously characterized epigenetic and transcriptional changes in brain disease states suggested significant overlap between genes regulated by memory formation and genes altered in memory-related neurological and neuropsychiatric diseases. These findings provide a comprehensive resource to aid in the identification of memory-relevant therapeutic targets. Our results shed new light on the gene expression and DNA methylation changes involved in memory formation, confirming that these processes are dynamic and experience-dependent. Finally, this work provides a roadmap for future studies to identify linkage of memory-associated genes to altered disease states.

SUBMITTER: Duke CG

PROVIDER: S-EPMC5473107 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Experience-dependent epigenomic reorganization in the hippocampus.

Duke Corey G CG Kennedy Andrew J AJ Gavin Cristin F CF Day Jeremy J JJ Sweatt J David JD

Learning & memory (Cold Spring Harbor, N.Y.) 20170615 7

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 following memory acquisition and became more pronounced after 24 h. Gene ontology analysis revealed significant enrichment of functional categories rel ...[more]

PMID: 28620075

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Project description:To date, numerous mathematical models have been proposed on the basis of some types of Hebbian synaptic learning to account for the activity-dependent development of orientation maps as well as neuronal orientation selectivity. These models successfully reproduced orientation map-like spatial patterns. Nevertheless, we still have questions: (1) How does synaptic rewiring occur in the visual cortex during the formation of orderly orientation maps in early life? (2) How does visual experience contribute to the maturation of orientation selectivity of visual cortical neurons and reorganize orientation maps? (3) How does the sensitive period for orientation plasticity end? In this study, we performed animal experiments and mathematical modeling to understand the mechanisms underlying synaptic rewiring for experience-dependent formation and reorganization of orientation maps. At first, we visualized orientation maps from the intrinsic signal optical imaging in area 17 of kittens reared under single-orientation exposure through cylindrical-lens-fitted goggles. The experiments revealed that the degree of expansion of cortical domains representing the experienced orientation depends on the age at which the single-orientation exposure starts. As a result, we obtained the sensitive period profile for orientation plasticity. Next, we refined our previously proposed mathematical model for the activity-dependent self-organization of thalamo-cortical inputs on the assumption that rewiring is caused by the competitive interactions among transient synaptic contacts on the same dendritic spine. Although various kinds of molecules have been reported to be involved in such interactions, we attempt to build a mathematical model to describe synaptic rewiring focusing on brain-derived neurotrophic factor (BDNF) and its related molecules. Performing computer simulations based on the refined model, we successfully reproduced orientation maps reorganized in kittens reared under single-orientation exposure as well as normal visual experience. We also reproduced the experimentally obtained sensitive period profile for orientation plasticity. The excellent agreement between experimental observations and theoretical reproductions suggests that the BDNF-induced competitive interaction among synaptic contacts from different axons on the same spine is an important factor for the experience-dependent formation and reorganization of orientation selectivity and orientation maps.

Dataset Information

Experience-dependent epigenomic reorganization in the hippocampus.

Publications

Experience-dependent epigenomic reorganization in the hippocampus.

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