Disrupted information processing in Fmr1-KO mouse layer 4 barrel cortex (Domanski et al 2019)


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Accession:266552
"Sensory hypersensitivity is a common and debilitating feature of neurodevelopmental disorders such as Fragile X Syndrome (FXS). How developmental changes in neuronal function culminate in network dysfunction that underlies sensory hypersensitivities is unknown. By systematically studying cellular and synaptic properties of layer 4 neurons combined with cellular and network simulations, we explored how the array of phenotypes in Fmr1-knockout (KO) mice produce circuit pathology during development. We show that many of the cellular and synaptic pathologies in Fmr1-KO mice are antagonistic, mitigating circuit dysfunction, and hence may be compensatory to the primary pathology. Overall, the layer 4 network in the Fmr1-KO exhibits significant alterations in spike output in response to thalamocortical input and distorted sensory encoding. This developmental loss of layer 4 sensory encoding precision would contribute to subsequent developmental alterations in layer 4-to-layer 2/3 connectivity and plasticity observed in Fmr1-KO mice, and circuit dysfunction underlying sensory hypersensitivity."
Reference:
1 . Domanski APF, Booker SA, Wyllie DJA, Isaac JTR, Kind PC (2019) Cellular and synaptic phenotypes lead to disrupted information processing in Fmr1-KO mouse layer 4 barrel cortex. Nat Commun 10:4814 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Thalamus;
Cell Type(s): Neocortex U1 L4 stellate GLU cell; Abstract integrate-and-fire leaky neuron;
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s): FMR1 FMRP;
Transmitter(s):
Simulation Environment: NEURON (web link to model); MATLAB (web link to model);
Model Concept(s): Development; Synaptic Plasticity; Sensory coding; Short-term Synaptic Plasticity; Simplified Models;
Implementer(s):
Search NeuronDB for information about:  Neocortex U1 L4 stellate GLU cell;
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