Stress-Induced Dendritic Remodeling in the Prefrontal Cortex is Circuit Specific
Open accessAbstract
Chronic stress exposure has been reported to induce dendritic remodeling in several brain regions, but it is not known whether individual neural circuits show distinct patterns of remodeling. The current study tested the hypothesis that the projections from the infralimbic (IL) area of the medial prefrontal cortex (mPFC) to the basolateral nucleus of the amygdala (BLA), a pathway relevant to stress-related mental illnesses like depression and post-traumatic stress disorder, would have a unique pattern of remodeling in response to chronic stress. The retrograde tracer FastBlue was injected into male rats' BLA or entorhinal cortex (EC) 1 week prior to 10 days of immobilization stress. After cessation of stress, FastBlue-labeled and unlabeled IL pyaramidal neurons were loaded with fluorescent dye Lucifer Yellow to visualize dendritic arborization and spine density. As has been previously reported, randomly selected (non-FastBlue-labeled) neurons showed stress-induced dendritic retraction in apical dendrites, an effect also seen in EC-projecting neurons. In contrast, BLA-projecting neurons showed no remodeling with stress, suggesting that this pathway may be particularly resilient against the effects of stress. No neurons showed stress-related changes in spine density, contrasting with reports that more dorsal areas of the mPFC show stress-induced decreases in spine density. Such region- and circuit-specificity in response to stress could contribute to the development of stress-related mental illnesses.
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Stress reduces dendrites in mPFC neurons involved with cortical-cortical processing but increases dendrites in mPFC neurons that project to and excite amygdala actions.
“An elegant study by Shansky and colleagues showed that stress reduces dendrites in mPFC neurons involved with cortical-cortical processing, but increases dendrites in the mPFC neurons that project to and excite amygdala actions.25”
From Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes. (2021) · cites this paper as [25]
The Results section reports dendritic retraction in randomly selected and entorhinal-cortex-projecting mPFC neurons, supporting the first part of the sentence. But it reports no stress-related increase—or other remodeling—in neurons projecting to the basolateral amygdala. The Introduction also says that stimulation of this pathway suppresses amygdala output, rather than exciting amygdala actions. The indexed copy provides no page number for the Results passage. (LLM, conf=0.93)
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Experimental — accuracy not yet measuredElevated glutamatergic transmission within discrete anatomical circuits may explain the targeted nature of gray matter changes within mood disorders.
“Elevated glutamatergic transmission within discrete anatomical circuits also may explain the targeted nature of gray matter changes within mood disorders (eg, affecting left more than right sgACC) (McEwen and Magarinos, 2001;Drevets and Price, 2005a;Shansky et al, 2009).”
From Neurocircuitry of Mood Disorders (2010) · cites this paper as Shansky et al, 2009
The Abstract reports circuit-specific dendritic remodeling after stress in rats, and the Functional Implications section suggests that a spared pathway might receive increased input and become overstimulated (page numbers not supplied). The paper does not establish elevated glutamatergic transmission as the cause of targeted gray-matter changes in mood disorders, nor does it address left–right differences in the sgACC. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe infralimbic cortex is involved in coping with chronic stress, eventually leading to structural changes and prefrontal dysfunction.
“The most ventral subdomain of the mPFC is the infralimbic cortex (IL) and is involved in coping with chronic stress eventually leading to structural changes and prefrontal dysfunction [5–11].”
From Development of prefrontal cortex (2022) · cites this paper as [9]
The Introduction describes the infralimbic cortex as part of a circuit that regulates amygdala activity, and the study reports chronic-stress-induced dendritic retraction in some infralimbic neurons. But the Abstract reports no remodeling in neurons projecting to the basolateral amygdala, while the Functional Implications section treats resulting circuit dysfunction as a possibility for future study, not an established consequence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredChronic exposure to uncontrollable stress causes loss of spines and dendrites in the prefrontal cortex (PFC).
“Chronic exposure to uncontrollable stress causes loss of spines and dendrites in the prefrontal cortex (PFC), a recently evolved brain region that provides top-down regulation of thought, action, and emotion.”
From Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes. (2021) · cites this paper as [25]
The Introduction (page not provided) reports dendritic retraction after chronic stress in rats, and the spine-density Results section reports prior findings of spine loss in two medial PFC regions. But this study found no spine-density loss in the infralimbic region and no dendritic remodeling in one circuit. The claim omits that regional and circuit specificity and calls the stress “uncontrollable,” whereas the paper describes its protocol as immobilization stress. (LLM, conf=0.87)
Experimental — accuracy not yet measuredEven within the PFC, there are circuit-specific alterations that lead to amygdala dominance with chronic stress: the subset of PFC neurons that activate the amygdala do not atrophy during stress (indeed, in females, these dendrites can be extended with stress), while the PFC neurons engaged in cortico-cortical connections show the expected loss of dendritic material.
“Even within the PFC, there are circuit-specific alterations that lead to amygdala dominance with chronic stress: the subset of PFC neurons that activate the amygdala do not atrophy during stress (indeed, in females, these dendrites can be extended with stress), while the PFC neurons engaged in cortico-cortical connections show the expected loss of dendritic material73.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [73]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Chronic stress impacts neural activity in both PL and IL cortex and leads to structural changes in IL cortex.
“In rodents, chronic stress also impacts neural activity in both PL and IL cortex [70] and leads to structural changes in IL cortex [71].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [71]
Neurons in the rat infralimbic PFC that project to the amygdala do not lose their dendrites in response to stress, highlighting the distinct response of amygdala circuits.
“Interestingly, recent data indicate that neurons in the rat infralimbic PFC that project to the amygdala do not lose their dendrites in response to stress, highlighting the distinct response of amygdala circuits113.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [113]
Sustained stress exposure induces loss of dendrites and spines in layer II/III pyramidal cells of rodent PFC and loss of the dendritic tufts of layer V pyramidal cells.
“Sustained stress exposure induces loss of dendrites and spines in layer II/III pyramidal cells of rodent PFC70–73 and loss of the dendritic tufts of layer V pyramidal cells74.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [73]
Citation 74 is attached to the claim about loss of layer V dendritic tufts. The Tissue Preparation, Cell Loading, Reconstruction, and Analysis section says that, although layer V neurons were observed, only layer II/III neurons were analyzed; the reported dendritic retraction therefore cannot verify the layer V claim. The copy does not establish that layer V tufts were unaffected either. (LLM, conf=0.78)
Experimental — accuracy not yet measuredReduced dendritic complexity largely agrees with changes in other brain regions.
“Reduced dendritic complexity largely agrees with changes in other brain regions [151, 152] and is associated with reduced excitatory input but increased intrinsic excitability [88, 89], which may reflect homeostatic self-tuning [153].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [151]
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“In rodents, chronic stress also impacts neural activity in both PL and IL cortex [70] and leads to structural changes in IL cortex [71].”
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Wallace, T., & Myers, B. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.737960 · Cited by 8 · see citing works
Layer-specific input to medial prefrontal cortex is linked to stress susceptibility
Solakoğlu, S. T., Erdener, Ş. E., Gliko, O., Can, A., Sümbül, U., & Eren-Koçak, E. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03258-x · Cited by 5 · see citing works
- Authors
- Shansky, R. M., Hamo, C., Hof, P. R., McEwen, B. S., & Morrison, J. H.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Rockefeller University (US)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-02-04
- Volume
- 19
- Issue
- 10
- Pages
- 2479-2484
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC2742599
- OpenAlex
- W2095787168
- Cited by
- 248
- References
- 35
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 12 · 2023: 10 · 2022: 9 · 2021: 20 · 2020: 12 · 2019: 26 · 2018: 10 · 2017: 16 · 2016: 23 · 2015: 20 · 2014: 15 · 2013: 11 · 2012: 17
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH-58911, P50MH058911, MH075506, F32MH075506)
- 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 remodeling, medial prefrontal cortex, infralimbic cortex, basolateral amygdala, entorhinal cortex, dendritic spine density, dendritic retraction, stress resilience, depression, post-traumatic stress disorder
- MeSH terms
- Amygdala, Animals, Dendrites, Fluorescent Dyes, Male, Neural Pathways, Neuronal Plasticity, Restraint, Physical, Stress, Physiological, Prefrontal Cortex, Microscopy, Confocal, Entorhinal Cortex, Rats
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