Altered striatal rhythmic activity in cylindromatosis knock-out mice due to enhanced GABAergic inhibition.
2016
Abstract Despite the highest expression in striatum, physiological function of cylindromatosis (CYLD), a deubiquitinating enzyme, remains unexplored. We found, in the present study, that the duration of spontaneous up-states in the striatum is shorter and membrane potential fluctuation preceding action potential and firing rate are increased in Cyld −/− mice. Excess striatal GABAergic inhibition likely plays the major role in this alteration as supported by the findings: (1) the levels of striatal GABA A and GABA B receptors in Cyld −/− mice are increased, (2) pharmacological blockade of GABA B receptors rescues the shortened up-state phenotype, and (3) pharmacological blockade of GABA A receptors rescues the power of beta frequency oscillations. Our results indicate that CYLD alters striatal network function by regulating the protein expression levels of GABA receptors.
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