Pattern and time course of immediate early gene expression in rat brain following acute stress
Abstract
The pattern and time course of brain activation in response to acute swim and restraint stress were examined in the rat by in situ hybridization using complementary RNA probes specific for transcripts encoding the products of the immediate early genes c-fos, c-jun and zif/268. A widespread pattern of c-fos messenger RNA expression was detected in response to these stressors; surprisingly, the expression patterns were substantially similar following both swim and restraint stress. A dramatic induction of c-fos messenger RNA was observed in numerous neo- and allocortical regions, the lateral septal nucleus, the hypothalamic paraventricular and dorsomedial nuclei, the anterior hypothalamic area, the lateral portion of the retrochiasmatic area, the medial and cortical amygdaloid nuclei, the periaqueductal gray, and the locus coeruleus; however, a prominent induction of c-fos was also seen in numerous additional subcortical and brainstem regions. Although not as widely expressed in response to stress as c-fos, induction of zif/268 messenger RNA was also detected throughout many brain areas; these regions were largely similar to those in which c-fos was induced, although in a number of regions zif/268 was expressed in regions devoid of c-fos messenger RNA. Few brain areas showed increased expression of c-jun following stress; these regions also showed induction of c-fos and/or zif/268. The time courses of expression of all three immediate early genes were similar, with peak levels observed at the 30 or 60 min time point, and a markedly reduced signal evident at 120 min post-stress. However, in a number of cases a delayed and/or prolonged induction was noted that may be indicative of secondary neuronal activation. A number of recent studies have attempted to define neural pathways which convey stress-related information to the hypothalamic-pituitary-adrenal axis. The present results reveal a widespread pattern of neuronal activation in response to acute swim or restraint stress. These findings may aid in the identification of stress-specific neural circuits and are thus likely to have important implications for our understanding of neuronal regulation of the stress response.
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“Amygdalar effects of the HPA axis have also been shown to be region and stressor specific (71, 72).”
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The bed nucleus of the stria terminalis (BST) is afferent to stress-sensitive hypothalamic neurons.
“BST is afferent to stress-sensitive hypothalamic neurons.19,47”
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Fos is a widely used marker to map neuronal activation throughout the brain after stress.
“we employed Fos, a widely used marker, to map neuronal activation throughout the brain after the two types of stress.16,17,19,45”
From Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress (2014) · cites this paper as [19]
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Self-citation
- Authors
- Cullinan, W. E., Herman, J. P., Battaglia, D. F., Akil, H., & Watson, S. J.
- Affiliations
- University of Michigan (US)
- University of Kentucky (US)
- Corresponding author
- Cullinan, W.E.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 1995-01
- Volume
- 64
- Issue
- 2
- Pages
- 477-505
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2091497325
- Cited by
- 1,056
- References
- 94
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 11 · 2023: 19 · 2022: 26 · 2021: 27 · 2020: 27 · 2019: 29 · 2018: 33 · 2017: 38 · 2016: 33 · 2015: 39 · 2014: 35 · 2013: 33 · 2012: 61
- FWCI
- 17.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k21da000265-01)
- National Institute of Mental Health (MH49698)
- National Institute on Drug Abuse (DA00265-12, DA 05452)
- 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 › Neuropeptides and Animal Physiology
- Keywords
- acute stress, immediate early genes, c-fos, c-Jun, Zif268, swim stress, restraint stress, brain gene expression, hypothalamic-pituitary-adrenal axis, amygdala, periaqueductal gray, locus coeruleus
- MeSH terms
- Animals, Brain, Caudate Nucleus, DNA-Binding Proteins, Hippocampus, Male, Raphe Nuclei, Restraint, Physical, RNA, Messenger, Septal Nuclei, Stress, Psychological, Swimming, Time Factors, Transcription Factors, Gene Expression, Genes, jun, Genes, fos, Rats, Sprague-Dawley, Immediate-Early Proteins, Rats, Early Growth Response Protein 1
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