Fluorescent proteins and genetically encoded biosensors

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(4), P. 1189 - 1214

Published: Jan. 1, 2023

The genetically encoded fluorescent sensors convert chemical and physical signals into light. They are powerful tools for the visualisation of physiological processes in living cells freely moving animals. protein is reporter module a biosensor. In this study, we first review history full emission spectra on structural basis. Then, discuss design Finally, briefly several major types biosensors that currently widely used based their molecular targets, which may be useful future biosensors.

Language: Английский

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A tool kit of highly selective and sensitive genetically encoded neuropeptide sensors

Science, Journal Year: 2023, Volume and Issue: 382(6672)

Published: Nov. 16, 2023

Neuropeptides are key signaling molecules in the endocrine and nervous systems that regulate many critical physiological processes. Understanding functions of neuropeptides vivo requires ability to monitor their dynamics with high specificity, sensitivity, spatiotemporal resolution. However, this has been hindered by lack direct, sensitive, noninvasive tools. We developed a series GRAB (G protein-coupled receptor activation‒based) sensors for detecting somatostatin (SST), corticotropin-releasing factor (CRF), cholecystokinin (CCK), neuropeptide Y (NPY), neurotensin (NTS), vasoactive intestinal peptide (VIP). These fluorescent sensors, which enable detection specific binding at nanomolar concentrations, establish robust tool kit studying release, function, regulation under both pathophysiological conditions.

Language: Английский

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System-wide mapping of peptide-GPCR interactions in C. elegans

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113058 - 113058

Published: Aug. 31, 2023

Neuropeptides and peptide hormones are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of peptidergic network roles many peptides remain elusive, as our insight into peptide-receptor interactions is limited GPCRs still orphan receptors. Here we report genome-wide peptide-GPCR interaction map in Caenorhabditis elegans. By reverse pharmacology screening over 55,384 possible interactions, identify 461 cognate couples uncover with specific complex combinatorial encoded across within single genes. These provide insights functions evolution. Combining dataset phylogenetic analysis supports co-evolution conservation at least 14 bilaterian systems C. This resource lays foundation for system-wide network.

Language: Английский

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Lights, fiber, action! A primer on in vivo fiber photometry

Neuron, Journal Year: 2023, Volume and Issue: 112(5), P. 718 - 739

Published: Dec. 15, 2023

Fiber photometry is a key technique for characterizing brain-behavior relationships in vivo. Initially, it was primarily used to report calcium dynamics as proxy neural activity via genetically encoded indicators. This generated new insights into brain functions including movement, memory, and motivation at the level of defined circuits cell types. Recently, opportunity discovery with fiber has exploded development an extensive range fluorescent sensors biomolecules neuromodulators peptides that were previously inaccessible critical advance, combined availability affordable "plug-and-play" recording systems, made monitoring molecules high spatiotemporal precision during behavior highly accessible. However, while opening exciting avenues research, rapid expansion applications occurred without coordination or consensus on best practices. Here, we provide comprehensive guide help end-users execute, analyze, suitably interpret studies.

Language: Английский

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Sensitive multicolor indicators for monitoring norepinephrine in vivo

Nature Methods, Journal Year: 2023, Volume and Issue: 20(9), P. 1426 - 1436

Published: July 20, 2023

Language: Английский

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Unlocking opioid neuropeptide dynamics with genetically encoded biosensors

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(9), P. 1844 - 1857

Published: July 15, 2024

Abstract Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for precise dissection their complex and diverse dynamics circuit-specific manner. Opioid peptides modulate pain, reward aversion as such have high clinical relevance. To illuminate spatiotemporal endogenous opioid signaling brain, we developed class genetically encoded fluorescence sensors based on kappa, delta mu receptors: κLight, δLight µLight, respectively. We characterized pharmacological profiles these mammalian cells dissociated neurons. used κLight to identify electrical stimulation parameters trigger release scale dynorphin volume transmission brain slices. Using vivo fiber photometry mice, demonstrated utility detecting optogenetically driven observed differential response fearful rewarding conditions.

Language: Английский

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A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 18, 2025

The co-existence and co-transmission of neuropeptides small molecule neurotransmitters within individual neuron represent a fundamental characteristic observed across various species. However, the differences regarding their in vivo spatiotemporal dynamics underlying molecular regulation remain poorly understood. Here, we develop GPCR-activation-based (GRAB) sensor for detecting short neuropeptide F (sNPF) with high sensitivity resolution. Furthermore, investigate between sNPF acetylcholine (ACh) from same neurons. Interestingly, our findings reveal distinct release ACh. Notably, results indicate that synaptotagmins (Syt) are involved these two processes, as Syt7 Sytα release, while Syt1 ACh release. Thus, this high-performance GRAB provides robust tool studying shedding insights into unique distinguish neurotransmitters.

Language: Английский

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When the Locus Coeruleus Speaks Up in Sleep: Recent Insights, Emerging Perspectives

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 5028 - 5028

Published: April 30, 2022

For decades, numerous seminal studies have built our understanding of the locus coeruleus (LC), vertebrate brain’s principal noradrenergic system. Containing a numerically small but broadly efferent cell population, LC provides brain-wide modulation that optimizes network function in context attentive and flexible interaction with sensory environment. This review turns attention to LC’s roles during sleep. We show these go beyond down-scaled versions ones wakefulness. Novel dynamic assessments noradrenaline signaling activity uncover rich diversity patterns establish as an integral portion sleep regulation function. The could be involved beneficial functions for sleeping brain, even minute alterations its functionality may prove quintessential disorders.

Language: Английский

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Role of the locus coeruleus and basal forebrain in arousal and attention

Brain Research Bulletin, Journal Year: 2022, Volume and Issue: 188, P. 47 - 58

Published: July 23, 2022

Language: Английский

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Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations

Nature and Science of Sleep, Journal Year: 2023, Volume and Issue: Volume 15, P. 17 - 38

Published: Jan. 1, 2023

After a detailed description of orexins and their roles in sleep other medical disorders, we discuss here the current clinical evidence on effects dual (DORAs) or selective (SORAs) orexin receptor antagonists insomnia with aim to provide recommendations for further assessment context personalized precision medicine. In last decade, many trials have been conducted antagonists, which represent an innovative valid therapeutic option based multiple mechanisms action different biological circuits, both centrally peripherally, role wide range conditions are often associated insomnia. A very interesting aspect this new category drugs is that they limited abuse liability discontinuation does not seem significant rebound effects. Further studies efficacy DORAs required, especially children adolescents particular conditions, such as menopause. Which DORA most suitable each patient, comorbidities and/or concomitant treatments, should be focus careful research. On contrary, SORAs, some appropriate also patients psychiatric diseases, still at early stage and, therefore, do allow draw definite conclusions.

Language: Английский

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