Translation-relevant EEG phenotypes in a mouse model of Fragile X Syndrome.
Open accessAbstract
Identification of comparable biomarkers in humans and validated animal models will facilitate pre-clinical to clinical therapeutic pipelines to treat neurodevelopmental disorders. Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety, social and sensory processing deficits. Recent EEG studies in humans with FXS have identified neural oscillation deficits that include enhanced resting state gamma power and reduced inter-trial coherence of sound evoked gamma oscillations. To determine if analogous phenotypes are present in an animal model of FXS, we recorded EEGs in awake, freely moving Fmr1 knock out (KO) mice using similar stimuli as in the human studies. We report remarkably similar neural oscillation phenotypes in the Fmr1 KO mouse including enhanced resting state gamma power and reduced evoked gamma synchronization. The gamma band inter-trial coherence of neural response was reduced in both auditory and frontal cortex of Fmr1 KO mice stimulated with a sound whose envelope was modulated from 1 to 100 Hz, similar to that seen in humans with FXS. These deficits suggest a form of enhanced 'resting state noise' that interferes with the ability of the circuit to mount a synchronized response to sensory input, predicting specific sensory and cognitive deficits in FXS. The abnormal gamma oscillations are consistent with parvalbumin neuron and perineuronal net deficits seen in the Fmr1 KO mouse auditory cortex indicating that the EEG biomarkers are not only clinically relevant, but could also be used to probe cellular and circuit mechanisms of sensory hypersensitivity in FXS.
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There is enhanced N1 amplitude and reduced gamma phase locking in auditory ERPs in Fmr1 KO mice.
“There is also enhanced N1 amplitude and reduced gamma phase locking in auditory ERPs (Lovelace et al., 2018).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Lovelace et al., 2018
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- Authors
- Lovelace, J. W., Ethell, I. M., Binder, D. K., & Razak, K. A.
- Affiliations
- University of California, Riverside (US)
- Corresponding author
- Razak, Khaleel A.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 115
- Pages
- 39-48
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC5969806
- OpenAlex
- W2794978048
- Cited by
- 154
- References
- 66
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 20 · 2023: 12 · 2022: 24 · 2021: 23 · 2020: 18 · 2019: 14 · 2018: 4
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (1U54 HD082008-01)
- US Army Medical Research (W81XWH-15-1-0436)
- FRAXA Research Foundation
- 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 › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- fragile X syndrome, Fmr1 knockout mice, EEG biomarkers, gamma oscillations, inter-trial phase coherence, auditory cortex, parvalbumin neurons, perineuronal nets, sensory hypersensitivity, intellectual disability, neurodevelopmental disorders
- MeSH terms
- Acoustic Stimulation, Animals, Auditory Cortex, Disease Models, Animal, Electroencephalography, Fragile X Syndrome, Frontal Lobe, Male, Mice, Inbred C57BL, Phenotype, Mice, Knockout, Mice, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, Translational Research, Biomedical
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