Circuit level defects in the developing neocortex of fragile X mice
Open accessAbstract
Subtle alterations in how cortical network dynamics are modulated by different behavioral states could disrupt normal brain function and underlie symptoms of neuropsychiatric disorders, including Fragile X syndrome (FXS). Using two-photon calcium imaging and electrophysiology, we recorded spontaneous neuronal ensemble activity in mouse somatosensory cortex. Unanesthetized Fmr1(-/-) mice exhibited abnormally high synchrony of neocortical network activity, especially during the first two postnatal weeks. Neuronal firing rates were threefold higher in Fmr1(-/-) mice than in wild-type mice during whole-cell recordings manifesting Up/Down states (slow-wave sleep, quiet wakefulness), probably as a result of a higher firing probability during Up states. Combined electroencephalography and calcium imaging experiments confirmed that neurons in mutant mice had abnormally high firing and synchrony during sleep. We conclude that cortical networks in FXS are hyperexcitable in a brain state-dependent manner during a critical period for experience-dependent plasticity. These state-dependent network defects could explain the intellectual, sleep and sensory integration dysfunctions associated with FXS.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
At a single neuron level, cortical activity is high in mouse models of fragile X syndrome.
“At a single neuron level, cortical activity is high in mice models of Alzheimer's disease (Busche et al., 2008 ), fragile X syndrome (Goncalves, Anstey, Golshani, & Portera‐Cailliau, 2013 ), and Rett syndrome (Zhang, Peterson, Beyer, Frankel, & Zhang, 2014 ), and in these mice models, the abnormalities in cortical neuronal activity are associated with defects in inhibition.”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as Goncalves, Anstey, Golshani, & Portera‐Cailliau, 2013
The Abstract and Discussion report elevated firing rates in individual cortical neurons of Fmr1–/– mice, supporting the fragile X portion of the claim. The increase was observed during particular brain states, especially Up/Down states and sleep, in developing mice; the sentence presents it more generally. The Discussion suggests impaired inhibition as a possible explanation, rather than establishing it as the cause. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAbnormally high basal activity in the cerebral cortex is also a feature in Alzheimer's disease and Fragile X syndrome mouse models.
“Abnormally high basal activity in the cerebral cortex is also a feature in Alzheimer's disease (Busche et al., 2008 ) and Fragile X syndrome (Goncalves et al., 2013 ) mouse models.”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as Goncalves et al., 2013
The Results report unusually high cortical firing rates in Fragile X model mice during quiet restfulness or sleep. The Discussion specifies that elevated firing occurs during Up/Down states and is brain-state dependent, so the unqualified description of high basal activity overstates the finding. The Alzheimer's disease portion is attributed to a different citation and is not assessed here. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn these mouse models, abnormalities in cortical neuronal activity are associated with defects in inhibition.
“At a single neuron level, cortical activity is high in mice models of Alzheimer's disease (Busche et al., 2008 ), fragile X syndrome (Goncalves, Anstey, Golshani, & Portera‐Cailliau, 2013 ), and Rett syndrome (Zhang, Peterson, Beyer, Frankel, & Zhang, 2014 ), and in these mice models, the abnormalities in cortical neuronal activity are associated with defects in inhibition.”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as Goncalves, Anstey, Golshani, & Portera‐Cailliau, 2013
In the mouse models of Alzheimer disease and Fragile X syndrome, high basal activity was also detected in the anesthetized state.
“In the mouse models of Alzheimer disease (Busche et al., 2008 ) and Fragile X syndrome (Goncalves et al., 2013 ), high basal activity was also detected in the anesthetized state”
From Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020) · cites this paper as Goncalves et al., 2013
The light-anesthesia regime minimizes the possibility that the mapped changes are the results of different brain states reflecting genotype-dependent sensitivity to anesthesia.
“The light-anesthesia regime also minimizes the possibility that the mapped changes are the results of different brain states reflecting genotype-dependent sensitivity to anesthesia, as it was previously suggested for Fmr1−/y mice (Goncalves et al. 2013).”
From Dysfunctional Autism Risk Genes Cause Circuit-Specific Connectivity Deficits With Distinct Developmental Trajectories (2018) · cites this paper as Goncalves et al. 2013
Fmr1 mutant mice are highly susceptible to seizures and exhibit abnormally high cortical network synchrony during juvenile stages.
“Consistently, Fmr1 mutant mice are highly susceptible to seizures 103 and exhibit abnormally high cortical network synchrony during juvenile stages 104 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [104]
Hypersynchrony is due to a higher than normal proportion of active pyramidal cells, which are intrinsically more excitable and have increased firing rates.
“Hypersynchrony is due to a higher than normal proportion of active pyramidal cells, which are intrinsically more excitable and have increased firing rates 104,105 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [104]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 56 · Cited by 279
- Authors
- Gonçalves, J. T., Anstey, J. E., Golshani, P., & Portera-Cailliau, C.
- Affiliations
- University of California, Los Angeles (US)
- Salk Institute for Biological Studies (US)
- Venue
- Nature Neuroscience
- Published
- 2013-06-02
- Volume
- 16
- Issue
- 7
- Pages
- 903-909
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3695061
- OpenAlex
- W2087965324
- Cited by
- 279
- References
- 56
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 13 · 2023: 20 · 2022: 21 · 2021: 23 · 2020: 21 · 2019: 31 · 2018: 26 · 2017: 27 · 2016: 24 · 2015: 16 · 2014: 26 · 2013: 2
- FWCI
- 15.02
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (RC1NS068093)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD054453)
- 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, neocortex, neuronal synchronization, hyperexcitability, sleep, quiet wakefulness, up-down states, spontaneous neuronal activity, somatosensory cortex, experience-dependent plasticity, intellectual disability
- MeSH terms
- Action Potentials, Age Factors, Analysis of Variance, Animals, Animals, Newborn, Calcium, Electric Stimulation, Electroencephalography, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Neurons, Wakefulness, Logistic Models, Patch-Clamp Techniques, Neocortex, Mice, Fragile X Messenger Ribonucleoprotein 1, Brain Waves
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
