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Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12156-61. doi: 10.1073/pnas.0900922106. Epub 2009 Jul 7.

Long-term sensory deprivation selectively rearranges functional inhibitory circuits in mouse barrel cortex.

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Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA.


Long-term whisker removal alters the balance of excitation and inhibition in rodent barrel cortex, yet little is known about the contributions of individual cells and synapses in this process. We studied synaptic inhibition in four major types of neurons in live tangential slices that isolate layer 4 in the posteromedial barrel subfield. Voltage-clamp recordings of layer 4 neurons reveal that fast decay of synaptic inhibition requires alpha1-containing GABA(A) receptors. After 7 weeks of deprivation, we found that GABA(A)-receptor-mediated inhibitory postsynaptic currents (IPSCs) in the inhibitory low-threshold-spiking (LTS) cell recorded in deprived barrels exhibited faster decay kinetics and larger amplitudes in whisker-deprived barrels than those in nondeprived barrels in age-matched controls. This was not observed in other cell types. Additionally, IPSCs recorded in LTS cells from deprived barrels show a marked increase in zolpidem sensitivity. To determine if the faster IPSC decay in LTS cells from deprived barrels indicates an increase in alpha1 subunit functionality, we deprived alpha1(H101R) mutant mice with zolpidem-insensitive alpha1-containing GABA(A) receptors. In these mice and matched wild-type controls, IPSC decay kinetics in LTS cells were faster after whisker removal; however, the deprivation-induced sensitivity to zolpidem was reduced in alpha1(H101R) mice. These data illustrate a change of synaptic inhibition in LTS cells via an increase in alpha1-subunit-mediated function. Because alpha1 subunits are commonly associated with circuit-specific plasticity in sensory cortex, this switch in LTS cell synaptic inhibition may signal necessary circuit changes required for plastic adjustments in sensory-deprived cortex.

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