Chronic stress-induced hippocampal dendritic retraction requires CA3 NMDA receptors
Open accessAbstract
Chronic stress induces dendritic retraction in the hippocampal CA3 subregion, but the mechanisms responsible for this retraction and its impact on neural circuitry are not well understood. To determine the role of NMDA (N-methyl-D-aspartic acid) receptor (NMDAR)-mediated signaling in this process, we compared the effects of chronic immobilization stress (CIS) on hippocampal dendritic morphology, hypothalamic-pituitary-adrenal (HPA) axis activation, and anxiety-related and hippocampus-dependent behaviors, in transgenic male mice in which the NMDAR had been selectively deleted in CA3 pyramidal cells and in non-mutant littermates. We found that CIS exposure for 10 consecutive days in non-mutant mice effectively induces HPA axis activation and dendritic retraction of CA3 short-shaft pyramidal neurons, but not CA3 long-shaft pyramidal neurons, suggesting a differential cellular stress response in this region. Dendritic reorganization of short-shaft neurons occurred throughout the longitudinal axis of the hippocampus and, in particular, in the ventral pole of this structure. We also observed a robust retraction of dendrites in dorsal CA1 pyramidal neurons in the non-mutant C57BL/6 mouse strain. Strikingly, chronic stress-induced dendritic retraction was not evident in any of the neurons in either CA3 or CA1 in the mutant mice that had a functional lack of NMDARs restricted to CA3 pyramidal neurons. Interestingly, the prevention of dendritic retraction in the mutant mice had a minimal effect on HPA axis activation and behavioral alterations that were induced by chronic stress. These data support a role for NMDAR-dependent glutamatergic signaling in CA3 in the cell-type specific induction of dendritic retraction in two hippocampal subregions following chronic stress.
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Chronic stress induces substantial dendritic retraction in CA3 pyramidal neurons, evidenced by a 20-30% decrease in apical dendritic length and branching complexity.
“Chronic stress induces substantial dendritic retraction in CA3 pyramidal neurons, evidenced by a 20–30% decrease in apical dendritic length and branching complexity [96].”
From Chronic Stress-Associated Depressive Disorders: The Impact of HPA Axis Dysregulation and Neuroinflammation on the Hippocampus—A Mini Review (2025) · cites this paper as [96]
The Results report reduced apical branch length in short-shaft CA3 pyramidal neurons after chronic stress, with reduced branch number also found in ventral CA3. The Discussion likewise describes retraction and reduced complexity in short-shaft neurons, but the copy does not give a 20–30% decrease, and the Results find no significant stress effect on apical length or branch number in long-shaft neurons. The claim therefore overgeneralizes the affected neurons and gives an unsupported magnitude. (LLM, conf=0.88)
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- Authors
- Christian, K. M., Miracle, A. D., Wellman, C. L., & Nakazawa, K.
- Affiliations
- National Institutes of Health (US)
- Indiana University Bloomington (US)
- Corresponding author
- Nakazawa, K.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 174
- Pages
- 26-36
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC3020251
- OpenAlex
- W2155603196
- Semantic Scholar
- e66d7a3ce6b1420d53e6792b6dd520ec805d543e
- Cited by
- 138
- References
- 42
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 8 · 2019: 8 · 2018: 9 · 2017: 9 · 2016: 9 · 2015: 10 · 2014: 18 · 2013: 9 · 2012: 14
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (ZIAMH002845, Z01MH002845)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- chronic stress, dendritic retraction, hippocampal CA3, NMDA receptor, restraint stress, HPA axis activation, CA1 pyramidal neurons, glutamatergic signaling, anxiety-like behavior, hippocampal subfields
- MeSH terms
- Adrenal Glands, Animals, Body Weight, Corticosterone, Dendrites, Discrimination Learning, Exploratory Behavior, Fear, Immobilization, Male, Memory, Short-Term, Motor Activity, Mutation, Stress, Psychological, Receptors, N-Methyl-D-Aspartate, Mice, Knockout, Mice, CA3 Region, Hippocampal
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