Heterogeneity of tremor mechanisms assessed by tremor-related cortical potential in mice.

Young-Gyun Park,Chungki Lee,Daesoo Kim,Sehyun Kim,Youngsoo Kim,Jee Hyun Choi,Sun Ha Paek,Ki-Young Chang

doi:10.1186/s13041-015-0093-2

Abstract

BackgroundIdentifying a neural circuit mechanism that is differentially involved in tremor would aid in the diagnosis and cure of such cases. Here, we demonstrate that tremor-related cortical potential (TRCP) is differentially expressed in two different mouse models of tremor.ResultsHybrid tremor analysis of harmaline-induced and genetic tremor in mice revealed that two authentic tremor frequencies for each type of tremor were conserved and showed an opposite dependence on CaV3.1 T-type Ca2+ channels. Electroencephalogram recordings revealed that α1−/−;α1G-/- mice double-null for the GABA receptor α1 subunit (Gabra1) and CaV3.1 T-type Ca2+ channels (Cacna1g), in which the tremor caused by the absence of Gabra1 is potentiated by the absence of Cacna1g, showed a coherent TRCP that exhibited an onset that preceded the initiation of behavioral tremor by 3 ms. However, harmaline-induced tremor, which is known to be abolished by α1G−/−, showed no TRCP.ConclusionsOur results demonstrate that the α1−/−;α1G−/− double-knockout tremor model is useful for studying cortical mechanisms of tremor.

Highlights

Identifying a neural circuit mechanism that is differentially involved in tremor would aid in the diagnosis and cure of such cases
Using pharmacogenetic dissection of tremor frequencizes and high-resolution electroencephalograzphic (EEG) techniques [13] combining with event-related potential analysis(ERP) [14,15,16,17], we reveal that abnormal cortical rhythmicity in the form of tremor-related cortical potential (TRCP) is differentially expressed between harmaline and genetic models of action tremor
Considering that the different tremor frequencies reflect the involvement of different neural circuit mechanisms [1,2], the two action tremor models appear to have distinct neural circuit mechanisms

Summary

Introduction

Identifying a neural circuit mechanism that is differentially involved in tremor would aid in the diagnosis and cure of such cases. Tremor is an involuntary rhythmic oscillation of body parts [1,2]. Various mechanism ranges from reflex loop to central oscillation has been proposed for the origin of oscillatory activity generating tremor [1,2]. Animal models of tremor have been contributed to examine those hypotheses. Harmaline is a plant-derived metabolite used to induce tremor in animals [3,4,5]. Either knockout of the Cacna1g gene encoding the CaV3.1 channel α1G subunit (α1G−/− mice) or pharmacological blockage of T-type Ca2+ channels in the inferior olive abolishes 10–15 Hz harmaline-induced tremor and the pathological oscillation [8], suggesting that

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