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Normal CA1 Place Fields but Discoordinated Network Discharge in a Fmr1-Null Mouse Model of Fragile X Syndrome
Talbot, Zoe Nicole Sparks, Fraser Todd Dvorak, Dino Curran, Bridget Mary Alarcon, Juan Marcos
Fenton, André Antonio
Talbot, Zoe Nicole
Sparks, Fraser Todd
Dvorak, Dino
Curran, Bridget Mary
Fenton, André Antonio
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Journal Title
Neuron
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Publication Date
2018-02
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Publication Volume
97
Publication Issue
3
Publication Begin
684
Publication End
697.e4
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PIIS0896627317312114.pdf
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Abstract
Silence of FMR1 causes loss of fragile X mental retardation protein (FMRP) and dysregulated translation at synapses, resulting in the intellectual disability and autistic symptoms of fragile X syndrome (FXS). Synaptic dysfunction hypotheses for how intellectual disabilities like cognitive inflexibility arise in FXS predict impaired neural coding in the absence of FMRP. We tested the prediction by comparing hippocampus place cells in wild-type and FXS-model mice. Experience-driven CA1 synaptic function and synaptic plasticity changes are excessive in Fmr1-null mice, but CA1 place fields are normal. However, Fmr1-null discharge relationships to local field potential oscillations are abnormally weak, stereotyped, and homogeneous; also, discharge coordination within Fmr1-null place cell networks is weaker and less reliable than wild-type. Rather than disruption of single-cell neural codes, these findings point to invariant tuning of single-cell responses and inadequate discharge coordination within neural ensembles as a pathophysiological basis of cognitive inflexibility in FXS. VIDEO ABSTRACT.
Citation
Talbot ZN, Sparks FT, Dvorak D, Curran BM, Alarcon JM, Fenton AA. Normal CA1 Place Fields but Discoordinated Network Discharge in a Fmr1-Null Mouse Model of Fragile X Syndrome. Neuron. 2018 Feb 7;97(3):684-697.e4. doi: 10.1016/j.neuron.2017.12.043. Epub 2018 Jan 18. PMID: 29358017; PMCID: PMC6066593.