Genetically encoded sensors for measuring histamine release both in vitro and in vivo

• Published in: Neuron (Cambridge, Mass.) Mass.), 2023-05, Vol.111 (10), p.1564-1576.e6
• Main Authors: Dong, Hui, Li, Mengyao, Yan, Yuqi, Qian, Tongrui, Lin, Yunzhi, Ma, Xiaoyuan, Vischer, Henry F., Liu, Can, Li, Guochuan, Wang, Huan, Leurs, Rob, Li, Yulong
• Format: Article
• Language: English
• Subjects: Animals; Brain; genetically encoded sensor; GRAB sensor; Histamine; Histamine Release; Hypothalamus; Mice; Receptors, G-Protein-Coupled; sleep-wake cycle
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2023.02.024

Histamine (HA) is a key biogenic monoamine involved in a wide range of physiological and pathological processes in both the central and peripheral nervous systems. Because the ability to directly measure extracellular HA in real time will provide important insights into the functional role of HA in complex circuits under a variety of conditions, we developed a series of genetically encoded G-protein-coupled receptor-activation-based (GRAB) HA (GRABHA) sensors with good photostability, sub-second kinetics, nanomolar affinity, and high specificity. Using these GRABHA sensors, we measured electrical-stimulation-evoked HA release in acute brain slices with high spatiotemporal resolution. Moreover, we recorded HA release in the preoptic area of the hypothalamus and prefrontal cortex during the sleep-wake cycle in freely moving mice, finding distinct patterns of HA dynamics between these specific brain regions. Thus, GRABHA sensors are robust tools for measuring extracellular HA transmission in both physiological and pathological processes. [Display omitted] •GRABHA sensors are genetically encoded GPCR-activation-based histamine (HA) sensors•GRABHA sensors enable specific HA detection with high spatiotemporal resolution•Two separate constructs expand the effective dynamic range of HA detection•GRABHA reveals distinct patterns of HA dynamics between different brain regions Dong et al. develop and validate a pair of genetically encoded GPCR-activation-based histamine sensors, which enable monitoring of extracellular histamine dynamics in acute brain slices and freely behaving mice with high spatiotemporal resolution. Using these sensors, they find distinct patterns of histamine dynamics in two brain regions during sleep-wake cycles.