Critical period inhibition of NKCC1 rectifies synapse plasticity in the somatosensory cortex and restores adult tactile response maps in fragile X mice
| Autor: | Samuel N. Smukowski, Carlos Portera-Cailliau, Qionger He, Jeffrey N. Savas, Jian Xu, Erica D. Arroyo, Claire Piochon, Anis Contractor |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine congenital hereditary and neonatal diseases and abnormalities Sensory processing medicine.medical_treatment Sensory system Biology bumetanide Somatosensory system Article Synapse Fragile X Mental Retardation Protein Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine synapse NKCC1 medicine Animals Solute Carrier Family 12 Member 2 Molecular Biology Mice Knockout Neurons Somatosensory Cortex Barrel cortex FMR1 critical period Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health 030104 developmental biology Fragile X Syndrome Synapses Knockout mouse Excitatory postsynaptic potential Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Molecular psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/s41380-018-0048-y |
| Popis: | Summary Sensory perturbations in visual, auditory and tactile perception are core problems in Fragile X Syndrome (FXS). In the Fmr1 knockout mouse model of FXS, the maturation of synapses and circuits during critical period (CP) development in the somatosensory cortex is delayed, but it is unclear how this contributes to altered tactile sensory processing in the mature CNS. Here we demonstrate that inhibiting the juvenile chloride co-transporter NKCC1, which contributes to altered chloride homeostasis in developing cortical neurons of FXS mice, rectifies the chloride imbalance in layer IV somatosensory cortex neurons and corrects the development of thalamocortical excitatory synapses during the CP. Comparison of protein abundances demonstrated that NKCC1 inhibition during early development caused a broad remodeling of the proteome in the barrel cortex. In addition, the abnormally large size of whisker-evoked cortical maps in adult Fmr1 knockout mice was corrected by rectifying the chloride imbalance during the early CP. These data demonstrate that correcting the disrupted driving force through GABAA receptors during the CP in cortical neurons restores their synaptic development, has an unexpectedly large effect on differentially expressed proteins, and produces a long-lasting correction of somatosensory circuit function in FXS mice. |
| Databáze: | OpenAIRE |
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