Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons
Open accessAbstract
The hippocampus and the amygdala are essential components of the neural circuitry mediating stress responses. The hippocampus, which provides negative feedback regulation of the stress response, is particularly vulnerable to degenerative changes caused by chronic stress. Unlike the hippocampus, relatively little is known about how stress affects the amygdala and the nature of its role in the stress response. Hence, we examined the effects of two different models of chronic stress on hippocampal and amygdaloid neuronal morphology in rats. In agreement with previous reports, chronic immobilization stress (CIS) induced dendritic atrophy and debranching in CA3 pyramidal neurons of the hippocampus. In striking contrast, pyramidal and stellate neurons in the basolateral complex of the amygdala exhibited enhanced dendritic arborization in response to the same CIS. Chronic unpredictable stress (CUS), however, had little effect on CA3 pyramidal neurons and induced atrophy only in BLA bipolar neurons. These results indicate that chronic stress can cause contrasting patterns of dendritic remodeling in neurons of the amygdala and hippocampus. Moreover, CIS, but not CUS, reduced open-arm activity in the elevated plus-maze. These findings raise the possibility that certain forms of chronic stress, by affecting specific neuronal elements in the amygdala, may lead to behavioral manifestations of enhanced emotionality. Thus, stress-induced structural plasticity in amygdala neurons may provide a candidate cellular substrate for affective disorders triggered by chronic stress.
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In the basolateral amygdala, chronic unpredictable stress produces dendritic atrophy.
“In the basolateral amygdala (BLA) chronic unpredictable stress also produced dendritic atrophy but chronic immobilization stress instead increased dendritic branching (Banasr and Duman, 2007;Vyas et al, 2002Vyas et al, , 2003)).”
From Neurocircuitry of Mood Disorders (2010) · cites this paper as Vyas et al, 2002
The Results section, “Effects of chronic unpredictable stress on dendritic morphology of amygdala neurons” (page not provided), reports dendritic atrophy in the BLA after chronic unpredictable stress. The effect was limited to bipolar/bitufted neurons; the paper reports no effect on BLA pyramidal or stellate neurons, a qualification the claim omits. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn animals, chronic stress results in prolonged release of glucocorticoids and leads to hypertrophy of the amygdala and nucleus accumbens, atrophy of the hippocampus and prefrontal cortex, and functional impairment of the PFC.
“In animals, chronic stress results in the prolonged release of glucocorticoids and leads to hypertrophy of the amygdala and nucleus accumbens, atrophy of the hippocampus and prefrontal cortex (PFC), and functional impairment of the PFC (44–55).”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [47]
The Discussion (page not provided) reports that chronic immobilization stress caused dendritic hypertrophy in basolateral amygdala neurons and dendritic atrophy in hippocampal CA3 neurons. It also says the pattern depended on the stress regimen. The paper does not establish prolonged glucocorticoid release, nucleus accumbens hypertrophy, or prefrontal cortex atrophy or functional impairment. (LLM, conf=0.90)
Experimental — accuracy not yet measuredNon-selective activation of BDNF/TrkB signaling in the amygdala leads to maladaptive plasticity resulting in overactivation of this brain region and exacerbated anxiety and fear responses.
“enhanced BDNF/TrkB signaling in the amygdala leads to maladaptive plasticity resulting in overactivation of this brain region and exacerbated anxiety and fear responses (47, 198–200)”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [47]
The Functional implications section reports that chronic immobilization stress increased anxiety-like behavior and suggests that stress-induced amygdala remodeling could contribute to abnormally high fear responses. It does not establish that BDNF/TrkB activation causes that remodeling or those responses; a TrkB study appears only in the References and concerns the hippocampus. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBy contrast to the PFC and hippocampus, dendrites in the amygdala expand in response to chronic stress exposure.
“By contrast to the PFC and hippocampus, dendrites in the amygdala expand in response to chronic stress exposure112.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [112]
The Discussion reports that chronic immobilization stress caused dendritic hypertrophy in basolateral amygdala pyramidal and stellate neurons, contrasting with atrophy in hippocampal CA3 neurons. The claim is broader than the finding: the paper does not examine the PFC, and its other chronic-stress regimen caused atrophy in a different amygdala neuron type rather than expansion. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn contrast to the PFC, chronic stress exposure increases dendritic growth in the amygdala, thus accentuating the imbalance of amygdala over PFC function.
“In contrast to the PFC, chronic stress exposure increases dendritic growth in the amygdala77, thus accentuating the imbalance of amygdala over PFC function.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [77]
The Discussion reports increased dendritic arborization in basolateral amygdala pyramidal and stellate neurons after chronic immobilization stress. It also reports that chronic unpredictable stress did not produce that growth and instead caused atrophy in a different amygdala neuron type. The citation supports the growth finding for a specific stress regimen, not chronic stress exposure generally; the PFC comparison is not the part directly cited. (LLM, conf=0.88)
Experimental — accuracy not yet measured
In the basolateral amygdala, chronic immobilization stress increases dendritic branching.
“In the basolateral amygdala (BLA) chronic unpredictable stress also produced dendritic atrophy but chronic immobilization stress instead increased dendritic branching (Banasr and Duman, 2007;Vyas et al, 2002Vyas et al, , 2003)).”
From Neurocircuitry of Mood Disorders (2010) · cites this paper as Vyas et al, 2002
Chronic immobilisation stress in rats results in significant dendritic atrophy of apical and basal dendrites of CA3 pyramidal neurons, with a more pronounced loss in apical dendrites.
“The authors revealed that chronic immobilisation stress in rats resulted in significant dendritic atrophy of apical and basal dendrites of CA3 pyramidal neurons, with a more pronounced loss in apical dendrites.”
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 [95]
Chronic stress causes atrophy of apical dendrites of pyramidal neurons in the CA3 region of the hippocampus.
“Animal studies revealed that chronic stress causes atrophy of apical dendrites of pyramidal neurons in the CA3 region of the hippocampus (Magarinos et al. 1996; Vyas et al. 2002; Watanabe et al. 1992).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Vyas et al. 2002
Individual brain regions are affected by stress in very different ways.
“This view is supported by recent evidence that individual brain regions are affected by stress in very different ways.”
From Episodic memory, perceptual memory, and their interaction: Foundations for a theory of posttraumatic stress disorder. (2014) · cites this paper as Vyas, Mitra, Rao, & Chattarji, 2002
The same stress experience produces dendritic atrophy and debranching in the hippocampus at the same time as producing enhanced dendritic arborization in the amygdala.
“a study of neuronal morphology showed that the same stress experience produced dendritic atrophy and debranching in the hippocampus at the same time as producing enhanced dendritic arborization in the amygdala”
From Episodic memory, perceptual memory, and their interaction: Foundations for a theory of posttraumatic stress disorder. (2014) · cites this paper as Vyas, Mitra, Rao, & Chattarji, 2002
In rodents, repeated stress results in dendritic atrophy and reduced glial cell counts in hippocampal regions as well as increased dendritic branching in the basolateral amygdala.
“In rodents, repeated stress results in dendritic atrophy and reduced glial cell counts in hippocampal regions (McEwen and Magarinos, 2001) as well as increased dendritic branching in the basolateral amygdala (Vyas et al., 2002).”
From Individual differences in amygdala-medial prefrontal anatomy link negative affect, impaired social functioning, and polygenic depression risk (2012) · cites this paper as Vyas et al., 2002
Stress increases dendritic arborization and spine density of the amygdala, with concomitant increases in anxiety-like behaviors.
“Specifically, studies of rodents show that stress increases dendritic arborization and spine density of the amygdala, with concomitant increases in anxiety-like behaviors (Vyas et al., 2002; Vyas et al., 2003, Mitra et al., 2005).”
From The impact of developmental timing for stress and recovery (2015) · cites this paper as Vyas et al., 2002
Stress-induced amygdala morphology and volume changes seem to persist.
“In contrast, stress-induced amygdala morphology and volume changes seem to persist (Vyas et al., 2002, Adamec et al., 2005, Tottenham et al., 2010).”
From The impact of developmental timing for stress and recovery (2015) · cites this paper as Vyas et al., 2002
Stress results in atrophy of the hippocampus and medial PFC (mPFC).
“By contrast, stress results in atrophy of the hippocampus and medial PFC (mPFC) (Magariños et al., 1997, Vyas et al., 2002, Radley et al., 2006).”
From The impact of developmental timing for stress and recovery (2015) · cites this paper as Vyas et al., 2002
Neuronal and synaptic remodeling in BLA PNs, along with enhanced glutamatergic transmission, has been repeatedly associated with the negative consequence of stress.
“Neuronal and synaptic remodeling in BLA PNs, along with enhanced glutamatergic transmission, has been repeatedly associated with the negative consequence of stress (14,33,34,40), and prevention of these changes is paralleled by a protection against stress-induced increases in anxiety-like behavior (26,41).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [14]
Repeated stress causes dendritic shortening in medial prefrontal cortex.
“Repeated stress causes dendritic shortening in medial prefrontal cortex (Sousa et al., 2000; Wellman, 2001; Vyas et al., 2002; Kreibich and Blendy, 2004; Cook and Wellman, 2004; Radley et al., 2004; Brown et al., 2005; Radley et al., 2005)”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Vyas et al., 2002
Repeated stress produces dendritic growth in neurons in amygdala.
“but produces dendritic growth in neurons in amygdala (Vyas et al., 2002)”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Vyas et al., 2002
Both acute and chronic stress increases spine synapse formation in amygdala.
“both acute and chronic stress also increases spine synapse formation in amygdala (Vyas et al., 2002)”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Vyas et al., 2002
Acute stress induces spine synapses in the CA1 region of hippocampus, and both acute and chronic stress increase spine synapse formation in amygdala, but chronic stress decreases it in hippocampus.
“Acute stress induces spine synapses in the CA1 region of hippocampus98 and both acute and chronic stress also increases spine synapse formation in amygdala,95-99 but chronic stress decreases it in hippocampus.77”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [95]
Repeated stress causes dendritic shortening in medial prefrontal cortex but produces dendritic growth in neurons in amygdala and orbitofrontal cortex.
“Repeated stress causes dendritic shortening in medial prefrontal cortex.89-95 but produces dendritic growth in neurons in amygdala,95 as well as in orbitofrontal cortex.96”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [95]
Behavioral correlates of remodeling in the prefrontal cortex include impairment in attention set shifting, possibly reflecting structural remodeling in the medial prefrontal cortex.
“Behavioral correlates of remodeling in the prefrontal cortex include impairment in attention set shifting, possibly reflecting structural remodeling in the medial prefrontal cortex.95”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [95]
Chronic stress results in an increase in dendritic arborization and spinogenesis on BLA pyramidal neurons, increasing their intrinsic excitability and afferent stimulation in a manner that correlates with heightened anxiety-like behavior.
“Additionally, multiple studies have found that chronic stress results in an increase in dendritic arborization and spinogenesis on BLA pyramidal neurons, increasing their intrinsic excitability and afferent stimulation in a manner that correlates with heightened anxiety-like behavior [70–72].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [70]
Acute traumatic stressors cause increased spine density on basolateral amygdala neurons, and chronic stress leads to expansion of basolateral amygdala dendrites.
“Acute traumatic stressors were found to cause increased spine density on basolateral amygdale (BlA) neurons and chronic stress leads to the expansion of BlA dendrites.”
From Neurobiological and Systemic Effects of Chronic Stress (2017) · cites this paper as [18]
Chronic stress causes dendritic shrinkage not only in CA3 and dentate gyrus neurons of hippocampus but also in medial amygdala and medial prefrontal cortex, while dendrites in basolateral amygdala and orbitofrontal cortex expand with chronic stress.
“Chronic stress causes dendritic shrinkage not only in CA3 and dentate gyrus neurons of hippocampus but also in medial amygdala and mPFC, while dendrites in BlA and orbitofrontal cortex expand with chronic stress.”
From Neurobiological and Systemic Effects of Chronic Stress (2017) · cites this paper as [18]
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- Authors
- Vyas, A., Mitra, R., Shankaranarayana Rao, B. S., & Chattarji, S.
- Affiliations
- Tata Institute of Fundamental Research (IN)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-08-01
- Volume
- 22
- Issue
- 15
- Pages
- 6810-6818
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758130
- OpenAlex
- W2136403062
- Semantic Scholar
- 587bd6bf61952d2c4d4fa8f4155737d79006655e
- Cited by
- 1,662
- References
- 51
- Citations by year
- 2026: 42 · 2025: 36 · 2024: 47 · 2023: 50 · 2022: 51 · 2021: 83 · 2020: 94 · 2019: 89 · 2018: 111 · 2017: 87 · 2016: 99 · 2015: 83 · 2014: 90 · 2013: 112 · 2012: 86
- FWCI
- 11.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research, India
- Directorate for Biological Sciences
- National Centre for Biological Sciences
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- chronic stress, dendritic remodeling, hippocampus, amygdala, restraint stress, chronic unpredictable mild stress, CA3 pyramidal cells, basolateral amygdala, stellate neurons, dendritic atrophy, dendritic branching, stress response, structural plasticity, anxiety-like behavior, emotionality, mood disorders
- MeSH terms
- Adrenal Glands, Amygdala, Animals, Anxiety, Body Weight, Chronic Disease, Dendrites, Disease Models, Animal, Hippocampus, Male, Neuronal Plasticity, Neurons, Organ Size, Restraint, Physical, Stress, Physiological, Rats, Wistar, Pyramidal Cells, Rats
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