Wang Yunong, Rodriguez Cristobal, Alden Sasha E, Choi Myung-Hoon, Alanis Kristen, Srinivasan Rahul, Baker Lane A
Department of Chemistry, Texas A&M University, College Station, TX 77845-3255, USA.
Department of Neuroscience and Experimental Therapeutics, Texas A&M University College of Medicine, Bryan, TX 77807, USA.
Sci Adv. 2024 Dec 13;10(50):eado9322. doi: 10.1126/sciadv.ado9322. Epub 2024 Dec 11.
Understanding the dynamic spatial and temporal release of neurotransmitters can help resolve long-standing questions related to chemical modulation of neurological circuits. Dopamine modulates function in a range of physiological processes and is key to transmission in addiction and neurological disorders. Studies at subcellular scales promise to help develop a broader understanding of dopamine release, diffusion, and receptor activation and how these processes lead to functional outcomes. Electrochemical measurements of dopamine release at individual cells have proven especially informative. We describe incorporation of fast-scan cyclic voltammetry for detection of dopamine release with subcellular spatial resolution and millisecond time resolution. The platform is benchmarked with standard redox probes and then applied to imaging stimulated release from subcellular locations of a coculture of dopaminergic neurons and astrocytes. Voltammetry reveals heterogeneity in release based on time, location, and neuron identity. We believe that this platform ultimately offers a window to understanding neurotransmission in pathophysiological models of disease where cell-cell communication is key.
了解神经递质的动态时空释放有助于解决与神经回路化学调节相关的长期问题。多巴胺调节一系列生理过程的功能,是成瘾和神经疾病传递的关键。亚细胞尺度的研究有望帮助更广泛地理解多巴胺的释放、扩散和受体激活,以及这些过程如何导致功能结果。已证明对单个细胞多巴胺释放进行电化学测量具有特别重要的信息价值。我们描述了采用快速扫描循环伏安法以亚细胞空间分辨率和毫秒级时间分辨率检测多巴胺释放。该平台先用标准氧化还原探针进行基准测试,然后应用于对多巴胺能神经元和星形胶质细胞共培养物亚细胞位置的刺激释放进行成像。伏安法揭示了基于时间、位置和神经元身份的释放异质性。我们相信,这个平台最终为理解细胞间通讯至关重要的疾病病理生理模型中的神经传递提供了一个窗口。