Membrane-associated glucocorticoid activity is necessary for modulation of long-term memory via chromatin modification
Open accessAbstract
Glucocorticoid hormones enhance the consolidation of long-term memory of emotionally arousing training experiences. This memory enhancement requires activation of the cAMP-dependent kinase pathway and the subsequent phosphorylation of cAMP response-element binding (CREB) protein. Here, we demonstrate that glucocorticoids enhance the consolidation of hippocampus-dependent and hippocampus-independent aspects of object recognition memory via chromatin modification. More specifically, systemic corticosterone increases histone acetylation, a form of chromatin modification, in both the hippocampus and insular cortex following training on an object recognition task. This led us to examine whether increasing histone acetylation via histone deacetylase (HDAC) inhibition enhances memory in a manner similar to corticosterone. We found a double dissociation between posttraining HDAC inhibitor infusion into the insular cortex and hippocampus on the enhancement of object recognition and object location memory, respectively. In determining the molecular pathway upstream of glucocorticoids' effects on chromatin modification, we found that activation of membrane-associated glucocorticoid receptors (GRs) and the subsequent interaction between phospho-CREB and CREB-binding protein (CBP) appear to be necessary for glucocorticoids to enhance memory consolidation via chromatin modification. In contrast, mineralocorticoid receptors (MRs) do not appear to be involved. The findings also indicate that glucocorticoid activity has differential influences on hippocampus-dependent and hippocampus-independent components of memory for objects.
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OPP memory was enhanced by post-sample microinjections of the HDAC inhibitor sodium butyrate into the dorsal hippocampus.
“OPP memory was enhanced by post-sample microinjections of the HDAC inhibitor sodium butyrate into the dorsal hippocampus”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Roozendaal et al., 2010
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- Authors
- Roozendaal, B., Hernandez, A., Cabrera, S. M., Hagewoud, R., Malvaez, M., Stefanko, D. P., Haettig, J., & Wood, M. A.
- Affiliations
- University Medical Center Groningen (NL)
- University of California, Irvine (US)
- University of Groningen (NL)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-04-06
- Volume
- 30
- Issue
- 14
- Pages
- 5037-5046
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2861482
- OpenAlex
- W2121227254
- Cited by
- 233
- References
- 41
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 13 · 2021: 8 · 2020: 13 · 2019: 10 · 2018: 12 · 2017: 15 · 2016: 22 · 2015: 16 · 2014: 25 · 2013: 22 · 2012: 19
- FWCI
- 16.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Science Foundation (0618211)
- Whitehall Foundation
- National Institute of Mental Health (R01MH081004)
- National Institute of General Medical Sciences (K12GM068524)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- glucocorticoids, corticosterone, long-term memory consolidation, object recognition memory, object location memory, histone acetylation, chromatin modification, histone deacetylase inhibition, CREB, CREB-binding protein, CREB phosphorylation, mineralocorticoid receptor, hippocampus, insula, emotional arousal
- MeSH terms
- Animals, Cell Membrane, Chromatin, Glucocorticoids, Male, Memory, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Glucocorticoid, Rats, Sprague-Dawley, Recognition, Psychology, Mice, Rats, Gene Knock-In Techniques
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