Multiplex Imaging of Dynamic Neurochemical Networks with Designed Far-red Dopamine Sensors

Overview

Journal bioRxiv

Date 2025 Jan 7

PMID 39763912

Authors

Yu Zheng

Ruyi Cai

Kui Wang

Junwei Zhang

Yizhou Zhuo

Hui Dong

Yuqi Zhang

Yifan Wang

Fei Deng

En Ji

Yiwen Cui

Shilin Fang

Xinxin Zhang

Kecheng Zhang

Jinxu Wang

Guochuan Li

Xiaolei Miao

Zhenghua Wang

Yuqing Yang

Shaochuang Li

Jonathan Grimm

Kai Johnsson

Eric Schreiter

Luke Lavis

Zhixing Chen

Yu Mu

Yulong Li

Affiliations

Soon will be listed here.

Abstract

Neurochemical signals like dopamine (DA) play a crucial role in a variety of brain functions through intricate interactions with other neuromodulators and intracellular signaling pathways. However, studying these complex networks has been hindered by the challenge of detecting multiple neurochemicals simultaneously. To overcome this limitation, we developed a single-protein chemigenetic DA sensor, HaloDA1.0, which combines a cpHaloTag-chemical dye approach with the G protein-coupled receptor activation-based (GRAB) strategy, providing high sensitivity for DA, sub-second response kinetics, and an extensive spectral range from far-red to near-infrared. When used together with existing green and red fluorescent neuromodulator sensors, Ca indicators, cAMP sensors, and optogenetic tools, HaloDA1.0 provides high versatility for multiplex imaging in cultured neurons, brain slices, and behaving animals, facilitating in-depth studies of dynamic neurochemical networks.

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