Abnormal vibrissa‐related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics
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A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus-maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within-session habituation to the closed arms on the part of wild-type controls. We noticed that the 5xFAD transgenics did not engage in the whisker-barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home-cage social behavior and impaired social recognition, and did not permit barbering by wild-type mice when pair-housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics' avoidance of the closed arms in the plus maze.
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5xFAD mice (6 months or older) prefer open arms due to anxiety or disrupted vibrissa inhibition.
“5xFAD mice (6-m or older) prefer open arms 134 due to anxiety or disrupted vibrissa inhibition 135 .”
From NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer’s disease (2025) · cites this paper as [135]
The Discussion supports disrupted vibrissal inhibition as a possible explanation for closed-arm avoidance, but explicitly says the open-arm behavior cannot be attributed to decreased anxiety. The Methods > Behavior section reports testing mice at 9–11 months, so this paper does not establish the claim for all mice aged 6 months or older. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn 5xFAD mice, significantly reduced PV-positive neuron numbers were shown in cingulate and motor cortices, cortical layer IV, and hippocampal CA1-3 and dentate gyrus subfields.
“In 5xFAD mice, significantly reduced PV-positive neuron numbers were shown in cingulate and motor cortices [127], as well as cells in the cortical layer IV [128] or the hippocampal CA1–3 and dentate gyrus subfields [126].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [128]
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- Authors
- Flanigan, T. J., Xue, Y., Kishan Rao, S., Dhanushkodi, A., & McDonald, M. P.
- Affiliations
- Department of Neurology
- University of Tennessee Health Science Center (US)
- Corresponding author
- McDonald, M. P.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2014-04-22
- Volume
- 13
- Issue
- 5
- Pages
- 488-500
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- PMC
- PMC4170055
- OpenAlex
- W1962780572
- Cited by
- 104
- References
- 61
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 13 · 2023: 11 · 2022: 16 · 2021: 20 · 2020: 11 · 2019: 6 · 2018: 4 · 2017: 3 · 2015: 3
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- onlinelibrary.wiley.com/termsAndConditions#vor (vor)
- Locations
- Genes Brain & Behavior (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Aging (R01AG031253, R01AG040230, R21AG041935)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- 5xFAD mice, Alzheimer's disease model, anxiety, elevated plus maze, habituation, barrel cortex, parvalbumin interneurons, social recognition, social behavior
- MeSH terms
- Alzheimer Disease, Animals, Brain, Interneurons, Phenotype, Social Behavior, Vibrissae, Amyloid beta-Protein Precursor, Maze Learning, Mice, Presenilin-1
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