A fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain

Ino, Daisuke; Tanaka, Yudai; Hibino, Hiroshi; Nishiyama, Masaaki

doi:10.1038/s41592-022-01597-x

Cited by 51 publications

(43 citation statements)

References 57 publications

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“…Moreover, multicolor imaging of RCaMP3 and cAMPinG1-ST revealed the interaction of Ca 2+ and cAMP at the population level. Therefore, RCaMP3 will contribute to further multicolor imaging, especially with recently developed green indicators (Duffet et al, 2022; Fenno et al, 2020; Ino et al, 2022; Unger et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A multicolor suite for deciphering population coding in calcium and cAMPin vivo

Yokoyama

Manita

Uwamori

et al. 2023

Preprint

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cAMP is a pivotal second messenger regulated by various upstream pathways including Ca2+ and G protein-coupled receptors (GPCRs). To decipherin vivocAMP dynamics, we rationally designed cAMPinG1, an ultrasensitive genetically encoded green cAMP indicator that outperformed its predecessors in both dynamic range and cAMP affinity. Two-photon cAMPinG1 imaging detected cAMP transients in the somata and dendritic spines of neurons in the mouse visual cortex on the order of tens of seconds. In addition, multicolor imaging with a highly sensitive new red Ca2+ indicator RCaMP3 allowed simultaneous measurement of population patterns in Ca2+ and cAMP in hundreds of neurons. We identified Ca2+-induced cAMP responses that represented specific information, such as direction selectivity in vision and locomotion, as well as GPCR-induced cAMP responses. Overall, our multicolor suite revealed that information encoded in Ca2+ and GPCRs signaling is integrated and stored as cAMP transients for longer periodsin vivo.

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Section: Discussionmentioning

confidence: 99%

A multicolor suite for deciphering population coding in calcium and cAMPin vivo

Yokoyama

Manita

Uwamori

et al. 2023

Preprint

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“…Future studies should further dissect the responsible cell types and physiological functions of OxtR signaling in the ARH. Recent advances in the real-time imaging of OxtR activities, for example, with a circularly permuted green fluorescent protein binding to OxtR ( Ino et al, 2022 ; Qian et al, 2022 ), would be useful for delineating the circuit mechanism and spatiotemporal dynamics of the Oxt-mediated suppression of hyperphagic obesity, such as by pinpointing the site of Oxt release.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice

Inada

Tsujimoto

Yoshida

et al. 2022

eLife

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Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (Oxt) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. Oxt has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of Oxt signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) of Oxt or Oxt receptor (Oxtr) has little effect on food intake. We herein show that acute conditional KO (cKO) of Oxt selectively in the adult PVH, but not in the supraoptic nucleus, markedly increases body weight and food intake, with an elevated level of plasma triglyceride and leptin. Intraperitoneal administration of Oxt rescues the hyperphagic phenotype of the PVH Oxt cKO model. Furthermore, we show that cKO of Oxtr selectively in the posterior hypothalamic regions, especially the arcuate hypothalamic nucleus, a primary center for appetite regulations, phenocopies hyperphagic obesity. Collectively, these data reveal that Oxt signaling in the arcuate nucleus suppresses excessive food intake.

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“…The development of genetically encoded GPCR-based fluorescent sensors for neuropeptides provides another new tool for probing neuropeptide signaling and diffusion. Recently, several groups have reported new genetically encoded sensors to monitor the release and dynamics of dynorphin, orexin, and oxytocin , in living animals. Li’s group reported a toolkit of G-protein-coupled receptor activation–based (GRAB) sensors for several neuropeptides, including SST, cholecystokinin, corticotropin-releasing factor, neuropeptide Y, neurotensin, and vasoactive intestinal peptide .…”

Section: Integration Of Neuropeptide Release With Neuropeptide Sensingmentioning

confidence: 99%

Understanding Neuropeptide Transmission in the Brain by Optical Uncaging and Release

Xiong

Wilson

Slesinger

et al. 2023

ACS Chem. Neurosci.

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Neuropeptides are abundant and essential signaling molecules in the nervous system involved in modulating neural circuits and behavior. Neuropeptides are generally released extrasynaptically and signal via volume transmission through G-protein-coupled receptors (GPCR). Although substantive functional roles of neuropeptides have been discovered, many questions on neuropeptide transmission remain poorly understood, including the local diffusion and transmission properties in the brain extracellular space. To address this challenge, intensive efforts are required to develop advanced tools for releasing and detecting neuropeptides with high spatiotemporal resolution. Because of the rapid development of biosensors and materials science, emerging tools are beginning to provide a better understanding of neuropeptide transmission. In this perspective, we summarize the fundamental advances in understanding neuropeptide transmission over the past decade, highlight the tools for releasing neuropeptides with high spatiotemporal solution in the brain, and discuss open questions and future directions in the field.

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A fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain

Cited by 51 publications

References 57 publications

A multicolor suite for deciphering population coding in calcium and cAMPin vivo

A multicolor suite for deciphering population coding in calcium and cAMPin vivo

Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice

Understanding Neuropeptide Transmission in the Brain by Optical Uncaging and Release

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