VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors.
VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors.
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DOI：
10.7554/elife.72981
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发表时间：
2022-02-14
期刊：
影响因子：
7.7
通讯作者：
Tanaka-Yamamoto K
中科院分区：
文献类型：
--
作者：
Baek SJ;Park JS;Kim J;Yamamoto Y;Tanaka-Yamamoto K
虽然小脑的改变与应激症状有关，但小脑对应激症状的确切作用仍有待阐明。在这里，我们展示了投射到腹侧被盖区(VTA)的小脑神经元在慢性应激诱导的小鼠行为改变发展中的关键作用。慢性化学激活小腿I区抑制浦肯野细胞可抑制糖尿病肾病大鼠c-Fos的表达，并抑制由慢性应激引起的悬尾实验或强迫游泳实验中的不动增加。基于腺相关病毒的电路标测和电生理记录相结合，确定了通过小脑深部齿状核(DN)从CRU I到VTA的网络连接。此外，慢性抑制投射到VTA的DN中的特定神经元可以防止应激小鼠表现出这种抑郁样行为，而这些神经元的慢性激活单独引发的行为变化与慢性应激引发的抑郁样行为相当。我们的结果表明，VTA投射的小脑神经元主动调节抑郁样行为的发展，增加了小脑可能是预防人类抑郁障碍的有效靶点的可能性。
Although cerebellar alterations have been implicated in stress symptoms, the exact contribution of the cerebellum to stress symptoms remains to be elucidated. Here, we demonstrated the crucial role of cerebellar neurons projecting to the ventral tegmental area (VTA) in the development of chronic stress-induced behavioral alterations in mice. Chronic chemogenetic activation of inhibitory Purkinje cells in crus I suppressed c-Fos expression in the DN and an increase in immobility in the tail suspension test or forced swimming test, which were triggered by chronic stress application. The combination of adeno-associated virus-based circuit mapping and electrophysiological recording identified network connections from crus I to the VTA via the dentate nucleus (DN) of the deep cerebellar nuclei. Furthermore, chronic inhibition of specific neurons in the DN that project to the VTA prevented stressed mice from showing such depression-like behavior, whereas chronic activation of these neurons alone triggered behavioral changes that were comparable with the depression-like behaviors triggered by chronic stress application. Our results indicate that the VTA-projecting cerebellar neurons proactively regulate the development of depression-like behavior, raising the possibility that cerebellum may be an effective target for the prevention of depressive disorders in human.
影响因子：
13.6
作者：
Phua SC;Tan YL;Kok AMY;Senol E;Chiam CJH;Lee CY;Peng Y;Lim ATJ;Mohammad H;Lim JX;Fu Y
通讯作者：
Fu Y