Altered striatal rhythmic activity in cylindromatosis knock-out mice due to enhanced GABAergic inhibition

Jie Zhang; Ming Chen; Bo Li; Binghua Lv; Kai Jin; Shudan Zheng; Li Yang; Cheng Long

doi:10.1016/j.neuropharm.2016.06.021

Altered striatal rhythmic activity in cylindromatosis knock-out mice due to enhanced GABAergic inhibition

Neuropharmacology. 2016 Nov;110(Pt A):260-267. doi: 10.1016/j.neuropharm.2016.06.021. Epub 2016 Jun 21.

Authors

Jie Zhang¹, Ming Chen¹, Bo Li¹, Binghua Lv¹, Kai Jin¹, Shudan Zheng¹, Li Yang², Cheng Long³

Affiliations

¹ School of Life Sciences, South China Normal University, Guangzhou 510631, PR China.
² School of Psychology, South China Normal University, Guangzhou 510631, PR China; Brain Science Institute, South China Normal University, Guangzhou 510631, PR China; Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou 510631, PR China; Center for Studies of Psychological Application, South China Normal University, Guangzhou 510631, PR China. Electronic address: yang_li@m.scnu.edu.cn.
³ School of Life Sciences, South China Normal University, Guangzhou 510631, PR China; Brain Science Institute, South China Normal University, Guangzhou 510631, PR China. Electronic address: longcheng@m.scnu.edu.cn.

PMID: 27342122
DOI: 10.1016/j.neuropharm.2016.06.021

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.

Keywords: Cyld; Down-states; GABA receptor; Striatum; Up-states.

MeSH terms

Animals
Beta Rhythm / drug effects
Beta Rhythm / physiology*
Corpus Striatum / drug effects
Corpus Striatum / metabolism*
Corpus Striatum / pathology
Cysteine Endopeptidases / deficiency*
Cysteine Endopeptidases / genetics
Deubiquitinating Enzyme CYLD
GABA-A Receptor Antagonists / pharmacology
GABA-B Receptor Antagonists / pharmacology
Membrane Potentials / drug effects
Membrane Potentials / physiology
Mice, Inbred C57BL
Mice, Knockout
Neural Inhibition / drug effects
Neural Inhibition / physiology*
Neurons / drug effects
Neurons / metabolism
Neurons / pathology
Receptors, GABA-A / metabolism*
Receptors, GABA-B / metabolism*
Ribonuclease, Pancreatic / metabolism
Tissue Culture Techniques
gamma-Aminobutyric Acid / metabolism

Substances

GABA-A Receptor Antagonists
GABA-B Receptor Antagonists
Receptors, GABA-A
Receptors, GABA-B
gamma-Aminobutyric Acid
Ang2 protein, mouse
Ribonuclease, Pancreatic
CYLD protein, mouse
Deubiquitinating Enzyme CYLD
Cysteine Endopeptidases