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

Abstract

Background: Identifying 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. Results: Hybrid 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 a1(-/-); a1G(-/-) mice double-null for the GABA receptor a1 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 a1G(-/-), showed no TRCP. Conclusions: Our results demonstrate that the a1(-/-); a1G(-/-) double-knockout tremor model is useful for studying cortical mechanisms of tremor.