Monitoring norepinephrine release<i>in vivo</i>using next-generation GRAB<sub>NE</sub>sensors

Summary Norepinephrine (NE) is an essential biogenic monoamine neurotransmitter, yet researches using prototype NE sensors were limited by their low sensitivities. Here, we developed next-generation versions of GPCR activation-based NE sensors (GRABNE2mand GRABNE2h) with a superior response, high sensitivity and selectivity to NE bothin vitroandin vivo. Notably, these sensors can detect NE release triggered by either optogenetic or behavioral stimuli in freely moving mice, producing robust signals in the locus coeruleus and hypothalamus. With the development of a novel transgenic mouse line, we recorded both NE release and calcium dynamics with dual-color fiber photometry throughout the sleep-wake cycle; moreover, dual-color mesoscopic imaging revealed cell type‒specific spatiotemporal dynamics of NE and calcium during sensory processing and locomotion. Thus, these new GRABNEsensors are valuable tools for monitoring the precise spatiotemporal release of NEin vivo, providing new insights into the physiological and pathophysiological roles of NE..

Medienart:

Preprint

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

bioRxiv.org - (2023) vom: 28. Juni Zur Gesamtaufnahme - year:2023

Sprache:

Englisch

Beteiligte Personen:

Feng, Jiesi [VerfasserIn]
Dong, Hui [VerfasserIn]
Lischinsky, Julieta [VerfasserIn]
Zhou, Jingheng [VerfasserIn]
Deng, Fei [VerfasserIn]
Zhuang, Chaowei [VerfasserIn]
Miao, Xiaolei [VerfasserIn]
Wang, Huan [VerfasserIn]
Xie, Hao [VerfasserIn]
Cui, Guohong [VerfasserIn]
Lin, Dayu [VerfasserIn]
Li, Yulong [VerfasserIn]

Links:

Volltext [kostenfrei]

Themen:

570
Biology

doi:

10.1101/2023.06.22.546075

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI039992225