最先端研究セミナー

招聘者： 田中（山本）　敬子  (Principal Researcher, Korea Institute of Science and Technology)

演題：Cerebellar regulation of chronic stress-induced depression

日時：2026年6月24日（水）　12：00-13：00

開催場所：発生医学研究所1階　カンファレンス室　On site + Zoom

※ZOOMミーティングのURLはMoodleの「S-HIGO最先端研究セミナーA、B」にてご確認ください。

https://md.kumamoto-u.ac.jp/course/view.php?id=136783

Abstract： 

The cerebellum is now recognized as a brain structure involved in a wide range of functions, including motor coordination and learning, cognitive processing, and emotional regulation. Although the precise mechanisms by which the cerebellum contributes to these functions remain to be fully elucidated, its broad projections to multiple brain regions suggest that cerebellar influences are mediated, at least in part, through modulation of specific neural circuits underlying these functions^1,2. One brain region targeted by output neurons from the deep cerebellar nuclei (DCN) is the ventral tegmental area (VTA), which is critically involved not only in reward and motivation, but also in stress responses. In line with the proposed role of cerebellar modulation of specific neural circuits, we found that DCN neurons projecting to the VTA (VTAp-DCN neurons) are activated during restraint stress (RS), and that their activity proactively regulates the development of chronic RS-induced depression-like behaviors³. We next investigated how the activity of VTAp-DCN neurons contributes to these behavioral alterations⁴. Repeated activation during chronic RS reduced vesicular glutamate transporter 2 (VGLUT2) expression in VTAp-DCN neurons innervating VTA dopamine neurons, resulting in decreased excitatory synaptic transmission onto VTA dopamine neurons and reduced dopamine release in the nucleus accumbens, a major target of VTA dopamine neurons. Notably, the reduction in VGLUT2 expression temporally coincided with the emergence of depression-like behaviors, suggesting a causal contribution to the behavioral alterations. Consistently, preventing the reduction in VGLUT2 expression through overexpression suppressed depression-like behaviors and restored both synaptic transmission and dopamine release. These findings indicate that repeated activation of VTAp-DCN neurons during chronic RS induces plastic changes characterized by reduced VGLUT2 expression, leading to depression-like behaviors through weakened excitatory transmission and impaired dopamine signaling. Thus, cerebellum-dependent presynaptic adaptations in the VTA provide a mechanistic link between chronic stress and depression-like behaviors.

担当分野：中枢性代謝制御学講座　戸田（5082)