Resources
Authors & Affiliations
Yizhou Zhuo, Bin Luo, Xinyang Yi, Hui Dong, Xiaolei Miao, Jinxia Wan, John Williams, Malcolm Campbell, Ruyi Cai, Tongrui Qian, Fengling Li, Sophia Weber, Lei Wang, Huan Wang, Yu Zheng, Marina Wolf, Yingjie Zhu, Mitsuko Watabe-Uchida, Yulong Li
Abstract
Dopamine (DA) is a crucial monoamine neurotransmitter involved in many physiological and pathological processes through a complex network of dopaminergic projections, and the ability to directly monitor DA dynamics is essential for understanding its physiological functions. Despite the widespread use of genetically-encoded dopamine fluorescent sensors in vivo, the detection of DA is often limited to highly innervated regions. Consequently, cortical DA detection has received comparatively little attention due to a lake of sensitivity of current generations of sensors. To address this gap, we have developed a series of green and red fluorescent G-protein-coupled receptor (GPCR) activation-based DA (GRABDA) sensors employing different DA receptor subtypes. These sensors display highly improved sensitivity, selectivity, and signal-to-noise properties, with subsecond response kinetics and the ability to detect a broad range of DA concentrations. Using these sensors, we have measured optogenetically-evoked and behaviorally-relevant DA release in mice, while concurrently monitoring neurochemical signaling in the nucleus accumbens, amygdala, and cortex. Furthermore, with these sensors, we have identified spatially-resolved heterogeneous cortical DA release during various behavioral tasks. Thus, these new DA sensors provide an extended toolbox for multifaceted in vivo DA imaging under a variety of complex behavior contexts, which can in turn promote the understanding of diverse aspects of dopamine biology.