Mild traumatic brain injury reduces spine density of projection neurons in the medial prefrontal cortex and impairs extinction of contextual fear memory
Open accessAbstract
Epidemiology studies have found that a comorbidity exists between traumatic brain injury (TBI) and stress-related disorders. However, the anatomical and cellular bases for this association is poorly understood. An inability to extinguish the memory of a traumatic event lies at the core of many stress-related disorders. Experimental studies have shown that the medial pre-frontal cortex (mPFC), especially the infralimbic (IL) cortex, is required for extinction and for storing the memory of extinction. The output from the central nucleus of amygdala projects to the lateral hypothalamus, paraventricular nucleus, and central gray to regulate heart rate, stress hormone release, and freezing behavior, respectively. Projection neurons of the IL (layers II/III pyramidal neurons) are thought to stimulate GABAergic neurons in the amygdala, which, in turn, inhibit central amygdala output and reduce fear expression. Thus, loss and/or altered morphology of projection neurons of IL as a result of a mild TBI (mTBI) can compromise their ability to effectively inhibit the central amygdala, allowing the original fear memory to drive behavior. Using lateral mild fluid percussion injury (mFPI) in rats, we found that mFPI did not reduce neuronal numbers in the IL, but caused a significant reduction in overall dendritic spine density of both basal and apical dendrites on layer II/III pyramidal neurons. Spine numbers on layer V/VI pyramidal neurons were not significantly changed as a result of mFPI.…
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TBI to posterior cortex in rats reduces PFC spine density and impairs working memory.
“as well as reducing PFC spine density and impairing working memory (Zhao et al., 2018)”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Zhao et al., 2018
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- Authors
- Zhao, J., Huynh, J., Hylin, M. J., O'Malley, J. J., Perez, A., Moore, A. N., & Dash, P. K.
- Affiliations
- Department of Neurobiology & Anatomy, The University of Texas McGovern Medical School, Houston, Texas.
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2018-01
- Volume
- 35
- Issue
- 1
- Pages
- 149-156
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- PMC
- PMC5757078
- OpenAlex
- W2727986884
- Cited by
- 39
- References
- 41
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 3
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Neurotrauma (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH)
- National Institutes of Health (W81XWH, NS086301)
- University of California, Davis
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- mild traumatic brain injury, dendritic spine density, medial prefrontal cortex, infralimbic cortex, contextual fear memory, fear extinction, central amygdala, projection neurons, fluid percussion injury, stress-related disorders, freezing behavior, pyramidal neurons
- MeSH terms
- Animals, Brain Concussion, Extinction, Psychological, Fear, Male, Memory, Rats, Sprague-Dawley, Prefrontal Cortex, Pyramidal Cells, Dendritic Spines, Rats
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