Maleeva Galyna, Matera Carlo, Roda Silvia, Colleoni Alessio, De Amici Marco, Gorostiza Pau
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology, Barcelona, Spain.
Networking Biomedical Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), ISCIII, Barcelona, Spain.
Med Res Rev. 2025 Sep;45(5):1407-1422. doi: 10.1002/med.22112. Epub 2025 Apr 10.
Dopaminergic neurotransmission is involved in several important brain functions, such as motor control, learning, reward-motivated behavior, and emotions. Dysfunctions of dopaminergic system may lead to the development of various neurological and psychiatric disorders, like Parkinson's disease, schizophrenia, depression, and addictions. Despite years of sustained research, it is not fully established how dopaminergic neurotransmission governs these important functions through a relatively small number of neurons that release dopamine. Light-driven neurotechnologies, based on the use of small light-regulated molecules or overexpression of light-regulated proteins in neurons, have greatly contributed to the advancement of our understanding of dopaminergic circuits and our ability to control them selectively. Here, we overview the current state-of-the-art of light-driven control of dopaminergic neurotransmission. While we provide a concise guideline for the readers interested in pharmacological, pharmacogenetic, and optogenetic approaches to modulate dopaminergic neurotransmission, our primary focus is on the usage of photocaged and photo-switchable small dopaminergic molecules. We argue that photopharmacology, photoswitchable molecules of varied modalities, can be employed in a wide range of experimental paradigms, providing unprecedent insights into the principles of dopaminergic control, and represent the most promising light-based therapeutic approach for spatiotemporally precise correction of dopamine-related neural functions and pathologies.
多巴胺能神经传递参与多种重要的大脑功能，如运动控制、学习、奖励驱动行为和情绪。多巴胺能系统功能障碍可能导致各种神经和精神疾病的发生，如帕金森病、精神分裂症、抑郁症和成瘾。尽管经过多年持续研究，但多巴胺能神经传递如何通过相对少量释放多巴胺的神经元来调控这些重要功能仍未完全明确。基于在神经元中使用小型光调控分子或光调控蛋白过表达的光驱动神经技术，极大地推动了我们对多巴胺能回路的理解以及选择性控制它们的能力。在此，我们概述多巴胺能神经传递光驱动控制的当前技术水平。虽然我们为对调节多巴胺能神经传递的药理学、药物遗传学和光遗传学方法感兴趣的读者提供了一个简要指南，但我们的主要重点是光笼蔽和光开关小型多巴胺能分子的应用。我们认为，光药理学，即具有多种模式的光开关分子，可用于广泛的实验范式，为多巴胺能控制原理提供前所未有的见解，并且是用于时空精确校正多巴胺相关神经功能和病理的最有前景的基于光的治疗方法。
