
慢性ストレスによるうつ様行動は、VTAドパミン神経の活動低下に関連し、その機序にTRPC6チャネルの発現低下が関与している。


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The slow-intrinsic-pacemaker dopaminergic (DA) neurons originating in the ventral tegmental area (VTA) are implicated in various mood- and emotion-related disorders, such as anxiety, fear, stress and depression. Abnormal activity of projection-specific VTA DA neurons is the key factor in the development of these disorders. Here, we describe the crucial role for the NALCN and TRPC6, non-selective cation channels in mediating the subthreshold inward depolarizing current and driving the firing of action potentials of VTA DA neurons in physiological condition. Furthermore, we demonstrate that down-regulation of TRPC6 protein expression in the VTA DA neurons likely contributes to the reduced activity of projection-specific VTA DA neuron in chronic mild unpredictable stress (CMUS) depressive mice. In consistent with these, selective knockdown of TRPC6 channels in the VTA DA neurons conferred mice with depression-like behavior. This current study suggests down-regulation of TRPC6 expression/function is involved in reduced VTA DA neuron firing and chronic stress-induced depression-like behavior of mice.

### Competing Interest Statement

The authors have declared no competing interest.

The cation channel mechanisms of subthreshold inward depolarizing currents in the VTA dopaminergic neurons and their roles in the chronic-stress-induced depression-like behavior

慢性ストレス誘発うつ様行動における-vta-ドパミン神経の活動低下とtrpc6-チャネルの役割


慢性ストレス誘発うつ様行動における VTA ドパミン神経の活動低下とTRPC6 チャネルの役割
