美国爱因斯坦医学院Kamran Khodakhah团队发现，小脑直接调节黑质多巴胺能活动。该研究于2024年1月25日在线发表于国际一流学术期刊《自然—神经科学》。

据研究人介绍，有证据表明，小脑和基底神经节之间存在直接的相互联系，这对长期以来认为这些结构独立运作的观点提出了挑战。解剖学研究表明，小脑存在向黑质紧密相连（SNc）的投射，但这些连接（Cb-SNc）的性质和功能尚不清楚。

研究人员在小鼠身上发现，Cb-SNc投射与SNc中的多巴胺能神经元和非多巴胺能神经元形成单突触谷氨酸能突触。光遗传激活SNc中的Cb-SNc轴突与SNc活动增加、纹状体多巴胺水平升高和运动增加有关。在行为过程中，Cb-SNc投射在走动和单侧杠杆操作前被双侧激活。Cb-SNc投射对水奖赏表现出显著的激活，而对甜水则表现出更高的激活，这表明该通路也编码奖赏价值。因此，小脑可以直接、快速和有效地调节基底神经节多巴胺水平，并传递与运动启动、活力和奖赏处理相关的信息。

附：英文原文

Title: The cerebellum directly modulates the substantia nigra dopaminergic activity

Author: Washburn, Samantha, Oate, Maritza, Yoshida, Junichi, Vera, Jorge, Bhuvanasundaram, Ramakrishnan, Khatami, Leila, Nadim, Farzan, Khodakhah, Kamran

Issue&Volume: 2024-01-25

Abstract: Evidence of direct reciprocal connections between the cerebellum and basal ganglia has challenged the long-held notion that these structures function independently. While anatomical studies have suggested the presence of cerebellar projections to the substantia nigra pars compacta (SNc), the nature and function of these connections (Cb–SNc) is unknown. Here we show, in mice, that Cb–SNc projections form monosynaptic glutamatergic synapses with dopaminergic and non-dopaminergic neurons in the SNc. Optogenetic activation of Cb–SNc axons in the SNc is associated with increased SNc activity, elevated striatal dopamine levels and increased locomotion. During behavior, Cb–SNc projections are bilaterally activated before ambulation and unilateral lever manipulation. Cb–SNc projections show prominent activation for water reward and higher activation for sweet water, suggesting that the pathway also encodes reward value. Thus, the cerebellum directly, rapidly and effectively modulates basal ganglia dopamine levels and conveys information related to movement initiation, vigor and reward processing.

DOI: 10.1038/s41593-023-01560-9

Source: https://www.nature.com/articles/s41593-023-01560-9