Reduced anxiety, conditioned fear, and hippocampal long-term potentiation in transient receptor potential vanilloid type 1 receptor-deficient mice
Open accessAbstract
The transient receptor potential vanilloid type 1 channel (TRPV1) (formerly called vanilloid receptor VR1) is known for its key role of functions in sensory nerves such as perception of inflammatory and thermal pain. Much less is known about the physiological significance of the TRPV1 expression in the brain. Here we demonstrate that TRPV1 knock-out mice (TRPV1-KO) show less anxiety-related behavior in the light-dark test and in the elevated plus maze than their wild-type littermates with no differences in locomotion. Furthermore, TRPV1-KO mice showed less freezing to a tone after auditory fear conditioning and stress sensitization. This reduction of conditioned and sensitized fear could not be explained by alterations in nociception. Also, tone perception per se was unaffected, as revealed by determination of auditory thresholds through auditory brainstem responses and distortion-product otoacoustic emissions. TRPV1-KO showed also less contextual fear if assessed 1 d or 1 month after strong conditioning protocols. These impairments in hippocampus-dependent learning were mirrored by a decrease in long-term potentiation in the Schaffer collateral-commissural pathway to CA1 hippocampal neurons. Our data provide first evidence for fear-promoting effects of TRPV1 with respect to both innate and conditioned fear and for a decisive role of this receptor in synaptic plasticity.
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TRPV1 acts as an ionotropic counterpart to CB1R and promotes fear- and anxiety-related responses in rodents.
“there is growing indication that TRPV1 acts as a ionotropic counterpart to the CB1R resulting in the promotion of fear- and anxiety-related responses in rodents”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Marsch et al., 2007
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- Authors
- Marsch, R., Foeller, E., Rammes, G., Bunck, M., Kössl, M., Holsboer, F., Zieglgänsberger, W., Landgraf, R., Lutz, B., & Wotjak, C. T.
- Affiliations
- Max Planck Society (DE)
- Goethe University Frankfurt (DE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-01-24
- Volume
- 27
- Issue
- 4
- Pages
- 832-839
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672910
- OpenAlex
- W2089362566
- Cited by
- 359
- References
- 53
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 13 · 2022: 10 · 2021: 15 · 2020: 22 · 2019: 15 · 2018: 15 · 2017: 17 · 2016: 16 · 2015: 15 · 2014: 31 · 2013: 12 · 2012: 28
- FWCI
- 14.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Volkswagen Foundation
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- TRPV1, vanilloid receptor, anxiety, fear conditioning, stress sensitization, contextual fear, hippocampal long-term potentiation, Schaffer collateral-commissural pathway, CA1 neurons, synaptic plasticity, auditory fear conditioning, TRPV1 knockout mice, tone perception
- MeSH terms
- Animals, Anxiety, Conditioning, Psychological, Fear, Hippocampus, Male, Mice, Inbred C57BL, Synaptic Transmission, Neuronal Plasticity, Long-Term Potentiation, Mice, Knockout, TRPV Cation Channels, Mice
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