Normal CA1 Place Fields but Discoordinated Network Discharge in a Fmr1-Null Mouse Model of Fragile X Syndrome

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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: Talbot et al. report normal location-specific hippocampus CA1 place cell responses, but dysregulated synaptic function and discoordinated spike timing in fragile X syndrome (FXS) model mice, pointing to abnormally timed interactions between normally tuned single-neuron responses in FXS-associated intellectual disability and autism.




Talbot, Z. N., Sparks, F. T., Dvorak, D., Curran, B. M., Alarcon, J. M., & Fenton, A. A. (2018). Normal CA1 Place Fields but Discoordinated Network Discharge in a Fmr1-Null Mouse Model of Fragile X Syndrome. Neuron, 97(3), 684-697.e4.

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