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Fragile X Mental Retardation Protein Is Required for Rapid Experience-Dependent Regulation of the Potassium Channel Kv3.1b
Open accessAbstract
Fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates synaptic plasticity by repressing translation of specific mRNAs. We found that FMRP binds mRNA encoding the voltage-gated potassium channel Kv3.1b in brainstem synaptosomes. To explore the regulation of Kv3.1b by FMRP, we investigated Kv3.1b immunoreactivity and potassium currents in the auditory brainstem sound localization circuit of male mice. The unique features of this circuit allowed us to control neuronal activity in vivo by exposing animals to high-frequency, amplitude-modulated stimuli, which elicit predictable and stereotyped patterns of input to the anterior ventral cochlear nucleus (AVCN) and medial nucleus of the trapezoid body (MNTB). In wild-type (WT) animals, Kv3.1b is expressed along a tonotopic gradient in the MNTB, with highest levels in neurons at the medial, high-frequency end. At baseline,Fmr1−/−mice, which lack FMRP, displayed dramatically flattened tonotopicity in Kv3.1b immunoreactivity and K+currents relative to WT controls. Moreover, after 30 min of acoustic stimulation, levels of Kv3.1b immunoreactivity were significantly elevated in both the MNTB and AVCN of WT, but not Fmr1−/−, mice. These results suggest that FMRP is necessary for maintenance of the gradient in Kv3.1b protein levels across the tonotopic axis of the MNTB, and are consistent with a role for FMRP as a repressor of protein translation. Using numerical simulations, we demonstrate that Kv3.1b tonotopicity may be required for accurate encoding of stimulus features such as modulation rate, and that disruption of this gradient, as occurs in Fmr1−/−animals, degrades processing of this information.
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“However, FMRP is expressed across the auditory system and the observed cortical habituation deficits may have multiple origins (Strumbos et al., 2010; Wang et al., 2014; Rotschafer et al., 2015).”
From Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome (2016) · cites this paper as Strumbos et al., 2010
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Metadata
- Authors
- Strumbos, J. G., Brown, M. R., Kronengold, J., Polley, D. B., & Kaczmarek, L. K.
- Affiliations
- Yale University (US)
- Massachusetts Eye and Ear Infirmary (US)
- Corresponding author
- Kaczmarek, Leonard K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-08-04
- Volume
- 30
- Issue
- 31
- Pages
- 10263-10271
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3485078
- OpenAlex
- W2034460847
- Cited by
- 135
- References
- 56
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 11 · 2021: 7 · 2020: 14 · 2019: 14 · 2018: 10 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 7 · 2013: 9 · 2012: 5
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- FRAXA Research Foundation
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders (DC001919, R01DC009836, R03DC009488, DC009488, R01DC001919)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- FMRP, voltage-gated potassium channels, medial nucleus of the trapezoid body, Fmr1 knockout mice, synaptic plasticity, translation repression, RNA-binding proteins
- MeSH terms
- Acoustic Stimulation, Animals, Auditory Pathways, Brain Stem, Immunohistochemistry, Male, Neurons, RNA, Messenger, Sound Localization, Blotting, Western, Evoked Potentials, Auditory, Brain Stem, Mice, Knockout, Mice, Shaw Potassium Channels, Fragile X Messenger Ribonucleoprotein 1
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