Expression of C‐fos‐like protein as a marker for neuronal activity following noxious stimulation in the rat
Abstract
C‐fos is a proto‐oncogene that is expressed within some neurons following depolarization. The protein product, c‐fos protein, can be identified by immunohistochemical techniques. Therefore, c‐fos expression might be used as a marker for neuronal activity throughout the neuraxis following peripheral stimulation. This study has analyzed patterns of c‐fos expression in both control and anesthetized animals and in anesthetized rats subjected to various forms of peripheral stimulation. Labeled cells were counted in the spinal cord, brainstem, hypothalamus, and thalamus. Little c‐fos immunoreactivity was found in control animals. Prolonged inhalational anesthesia increased the number of labeled cells at several brainstem sites. Noxious stimulation of anesthetized rats induced c‐fos within the neuraxis in patterns consistent with data obtained from electrophysiological studies and in additional locations for which few direct electrophysiological data are available, such as the ventrolateral medulla, the posterior hypothalamic nucleus, and the reuniens and paraventricular thalamic nuclei. Gentle mechanical stimulation was ineffective in inducing c‐fos‐like protein. The data suggest that c‐fos can be used as a transynaptic marker for neuronal activity following noxious stimulation. However, c‐fos is expressed only in some kinds of neurons following peripheral stimulation, and it therefore may be an incomplete marker for nociresponsive activity. In addition, at least a few neurons express c‐fos protein in the absence of noxious stimulation. Experiments analyzing c‐fos expression must be designed with care, as both extraneous stimuli and anesthetic depth influence the results.
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c-Fos expression is a well-established indicator of mouse brain activity.
“Expression of c-Fos, an immediate early-gene marker, is a well-established indicator of mouse brain activity24.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [24]
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 [16]
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- Authors
- Bullitt, E.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Bullitt, Elizabeth
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 1990-06-22
- Volume
- 296
- Issue
- 4
- Pages
- 517-530
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2167541848
- Cited by
- 1,059
- References
- 53
- Citations by year
- 2026: 19 · 2025: 44 · 2024: 38 · 2023: 58 · 2022: 39 · 2021: 45 · 2020: 35 · 2019: 28 · 2018: 32 · 2017: 16 · 2016: 14 · 2015: 22 · 2014: 15 · 2013: 17 · 2012: 18
- FWCI
- 22.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08ns001006-04, 5p01ns014899-20)
- National Institute of Neurological Disorders and Stroke (5PO1NS14899, 5K08NS01006)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- c-fos, neuronal activity markers, noxious stimulation, nociception, inhalational anesthesia, brainstem, hypothalamus, thalamus, ventrolateral medulla, posterior hypothalamic nucleus, nucleus reuniens, paraventricular thalamus, mechanical stimulation, anesthetized rats
- MeSH terms
- Animals, Brain Stem, Hot Temperature, Hypothalamus, Immunohistochemistry, Male, Pain, Physical Stimulation, Proto-Oncogene Proteins, Rats, Inbred Strains, Spinal Cord, Thalamus, Proto-Oncogene Proteins c-fos, Rats
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