生理多巴胺信号在亚秒级对纹状体动态调控的制约因素，这一成果由美国加州大学Sotiris C. Masmanidis研究组经过不懈努力而取得。2024年7月3日出版的《自然-神经科学》杂志发表了这一研究成果。

为了验证多巴胺能神经元对纹状体尖峰活动的影响，研究人员在监测行为小鼠腹侧纹状体尖峰反应的同时，瞬时改变了多巴胺水平。除非多巴胺释放量超过奖赏匹配水平，这些操作只会导致纹状体活动发生微弱变化。这些研究结果表明，相对于其他输入信号，多巴胺能神经元通常在纹状体动态亚秒级的调控中扮演着次要角色，并证明在生理和潜在非生理条件下多巴胺能神经元对大脑功能的重要性。

据悉，多巴胺能神经元在联想学习中起着至关重要的作用，但它们在亚秒级时间尺度上调节行为的能力仍存在争议。一般认为，多巴胺能神经元通过快速调节纹状体的尖峰活动来诱导某些行为；但也有一种观点认为，只有人为的高水平（即超生理水平）多巴胺信号才能在快速时间尺度上改变行为。这就提出了一种可能性，即在生理范围内，纹状体尖峰活动并不会受到多巴胺信号的强烈影响。

附：英文原文

Title: Constraints on the subsecond modulation of striatal dynamics by physiological dopamine signaling

Author: Long, Charltien, Lee, Kwang, Yang, Long, Dafalias, Theresia, Wu, Alexander K., Masmanidis, Sotiris C.

Issue&Volume: 2024-07-03

Abstract: Dopaminergic neurons play a crucial role in associative learning, but their capacity to regulate behavior on subsecond timescales remains debated. It is thought that dopaminergic neurons drive certain behaviors by rapidly modulating striatal spiking activity; however, a view has emerged that only artificially high (that is, supra-physiological) dopamine signals alter behavior on fast timescales. This raises the possibility that moment-to-moment striatal spiking activity is not strongly shaped by dopamine signals in the physiological range. To test this, we transiently altered dopamine levels while monitoring spiking responses in the ventral striatum of behaving mice. These manipulations led to only weak changes in striatal activity, except when dopamine release exceeded reward-matched levels. These findings suggest that dopaminergic neurons normally play a minor role in the subsecond modulation of striatal dynamics in relation to other inputs and demonstrate the importance of discerning dopaminergic neuron contributions to brain function under physiological and potentially nonphysiological conditions.

DOI: 10.1038/s41593-024-01699-z

Source: https://www.nature.com/articles/s41593-024-01699-z