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Altered integration of excitatory inputs onto the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X syndrome

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, January 2023
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (86th percentile)

Mentioned by

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15 news outlets
blogs
2 blogs
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44 X users
wikipedia
1 Wikipedia page

Citations

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1 Dimensions

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mendeley
16 Mendeley
Title
Altered integration of excitatory inputs onto the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X syndrome
Published in
Proceedings of the National Academy of Sciences of the United States of America, January 2023
DOI 10.1073/pnas.2208963120
Pubmed ID
Authors

Diana E. Mitchell, Soledad Miranda-Rottmann, Maxime Blanchard, Roberto Araya

Abstract

Layer 5 (L5) pyramidal neurons receive predictive and sensory inputs in a compartmentalized manner at their apical and basal dendrites, respectively. To uncover how integration of sensory inputs is affected in autism spectrum disorders (ASD), we used two-photon glutamate uncaging to activate spines in the basal dendrites of L5 pyramidal neurons from a mouse model of Fragile X syndrome (FXS), the most common genetic cause of ASD. While subthreshold excitatory inputs integrate linearly in wild-type animals, surprisingly those with FXS summate sublinearly, contradicting what would be expected of sensory hypersensitivity classically associated with ASD. We next investigated the mechanism underlying this sublinearity by performing knockdown of the regulatory β4 subunit of BK channels, which rescued the synaptic integration, a result that was corroborated with numerical simulations. Taken together, these findings suggest that there is a differential impairment in the integration of feedforward sensory and feedback predictive inputs in L5 pyramidal neurons in FXS and potentially other forms of ASD, as a result of specifically localized subcellular channelopathies. These results challenge the traditional view that FXS and other ASD are characterized by sensory hypersensitivity, proposing instead a hyposensitivity of sensory inputs and hypersensitivity of predictive inputs onto cortical neurons.

X Demographics

X Demographics

The data shown below were collected from the profiles of 44 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 19%
Student > Doctoral Student 2 13%
Student > Bachelor 1 6%
Student > Ph. D. Student 1 6%
Professor 1 6%
Other 2 13%
Unknown 6 38%
Readers by discipline Count As %
Neuroscience 5 31%
Psychology 2 13%
Agricultural and Biological Sciences 1 6%
Medicine and Dentistry 1 6%
Unknown 7 44%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 139. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 April 2023.
All research outputs
#299,297
of 25,487,317 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#5,489
of 103,216 outputs
Outputs of similar age
#7,361
of 475,761 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#117
of 875 outputs
Altmetric has tracked 25,487,317 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 103,216 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 39.5. This one has done particularly well, scoring higher than 94% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 475,761 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 875 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.