Altered striatal rhythmic activity in cylindromatosis knock-out mice due to enhanced GABAergic inhibition. (November 2016)

• Record Type: Journal Article
• Authors: Zhang, Jie; Chen, Ming; Li, Bo; Lv, Binghua; Jin, Kai; Zheng, Shudan; Yang, Li; Long, Cheng
• Is Part Of: Neuropharmacology. Volume 110(2016) Part A
• Page Start: 260
• Page End: 267
• Publication Date: 2016-11
• Subjects: Cyld -- Up-states -- Down-states -- GABA receptor -- Striatum; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2016.06.021
• Languages: English
• ISSNs: 0028-3908

Abstract

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 GABAA and GABAB receptors in Cyld −/− mice are increased, (2) pharmacological blockade of GABAB receptors rescues the shortened up-state phenotype, and (3) pharmacological blockade of GABAA 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. Highlights: The duration of up-states is shorter while the firing rate is higher in Cyld −/− mice. Membrane potential fluctuations preceding action potentials are lower in Cyld −/− mice. Striatal GABAA and GABAB receptor levels are increased in Cyld −/− mice. GABAB receptor antagonist rescues duration of up-states in Cyld −/− mice. GABAA receptor antagonist rescues power of beta frequency oscillations in Cyld −/− mice.