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Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes

Overview of attention for article published in Molecular Autism, September 2017
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (57th percentile)

Mentioned by

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5 tweeters

Citations

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40 Dimensions

Readers on

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117 Mendeley
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Title
Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes
Published in
Molecular Autism, September 2017
DOI 10.1186/s13229-017-0166-4
Pubmed ID
Authors

Joana Gonçalves, Inês R. Violante, José Sereno, Ricardo A. Leitão, Ying Cai, Antero Abrunhosa, Ana Paula Silva, Alcino J. Silva, Miguel Castelo-Branco

Abstract

Excitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased γ-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels. It is therefore important to clarify whether the E/I imbalance hypothesis holds true. We hypothesize that E/I may depend on distinct pre- and postsynaptic push-pull mechanisms that might be are region-dependent. In current study, we assessed two critical components of E/I regulation: the concentration of neurotransmitters and levels of GABA(A) receptors. Measurements were performed across the hippocampi, striatum, and prefrontal cortices by combined in vivo magnetic resonance spectroscopy (MRS) and molecular approaches in this ASD-related animal model, the Nf1(+/-) mouse. Cortical and striatal GABA/glutamate ratios were increased. At the postsynaptic level, very high receptor GABA(A) receptor expression was found in hippocampus, disproportionately to the small reduction in GABA levels. Gabaergic tone (either by receptor levels change or GABA/glutamate ratios) seemed therefore to be enhanced in all regions, although by a different mechanism. Our data provides support for the hypothesis of E/I imbalance in NF1 while showing that pre- and postsynaptic changes are region-specific. All these findings are consistent with our previous physiological evidence of increased inhibitory tone. Such heterogeneity suggests that therapeutic approaches to address neurochemical imbalance in ASD may need to focus on targets where convergent physiological mechanisms can be found.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 117 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 117 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 23 20%
Student > Bachelor 19 16%
Student > Master 15 13%
Researcher 14 12%
Student > Doctoral Student 6 5%
Other 15 13%
Unknown 25 21%
Readers by discipline Count As %
Neuroscience 30 26%
Psychology 13 11%
Agricultural and Biological Sciences 11 9%
Medicine and Dentistry 9 8%
Biochemistry, Genetics and Molecular Biology 5 4%
Other 14 12%
Unknown 35 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 31 May 2019.
All research outputs
#8,101,533
of 15,149,790 outputs
Outputs from Molecular Autism
#379
of 487 outputs
Outputs of similar age
#115,633
of 275,564 outputs
Outputs of similar age from Molecular Autism
#1
of 1 outputs
Altmetric has tracked 15,149,790 research outputs across all sources so far. This one is in the 46th percentile – i.e., 46% of other outputs scored the same or lower than it.
So far Altmetric has tracked 487 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 28.7. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
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 275,564 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them