"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]
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