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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The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(8)

Published: Feb. 20, 2025

While it is known that endocannabinoids (eCB) modulate multiple neuronal functions, the molecular mechanism governing their release and transport remains elusive. Here, we propose an "on-demand release" model, wherein formation of microvesicles, a specific group extracellular vesicles (EVs) containing eCB, 2-arachidonoylglycerol (2-AG), important step. A coculture model system combines reporter cell line expressing fluorescent eCB sensor, G protein-coupled receptor-based (GRAB)eCB2.0, cells revealed neurons EVs 2-AG, but not anandamide, in stimulus-dependent process regulated by protein kinase C, Diacylglycerol lipase, Adenosinediphosphate (ADP) ribosylation factor 6 (Arf6), which was sensitive to inhibitors facilitated diffusion. vesicle contained approximately 2,000 2-AG molecules. Accordingly, hippocampal eCB-mediated synaptic plasticity modulated Arf6 inhibitors. The supported mathematical analysis, offers cohesive framework for understanding trafficking at level suggests microvesicles carrying signaling lipids membrane regulate functions parallel canonical vesicles.

Language: Английский

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Characterizing Cortex-Wide Dynamics with Wide-Field Calcium Imaging

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(19), P. 4160 - 4168

Published: April 23, 2021

The brain functions through coordinated activity among distributed regions. Wide-field calcium imaging, combined with improved genetically encoded indicators, allows sufficient signal-to-noise ratio and spatiotemporal resolution to afford a unique opportunity capture cortex-wide dynamics on moment-by-moment basis in behaving animals. Recent applications of this approach have been uncovering cortical at unprecedented scales during various cognitive processes, ranging from relatively simple sensorimotor integration more complex decision-making tasks. In review, we will highlight recent scientific advances enabled by wide-field imaging mice. We then summarize several technical considerations future opportunities for uncover large-scale circuit dynamics.

Language: Английский

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In vivo endocannabinoid dynamics at the timescale of physiological and pathological neural activity

Neuron, Journal Year: 2021, Volume and Issue: 109(15), P. 2398 - 2403.e4

Published: Aug. 1, 2021

Language: Английский

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

Nature Methods, Journal Year: 2022, Volume and Issue: 19(10), P. 1286 - 1294

Published: Sept. 22, 2022

Abstract Oxytocin (OT), a hypothalamic neuropeptide that acts as neuromodulator in the brain, orchestrates variety of animal behaviors. However, relationship between brain OT dynamics and complex behaviors remains largely elusive, partly because lack suitable technique for its real-time recording vivo. Here, we describe MTRIA , G-protein-coupled receptor-based green fluorescent sensor has large dynamic range, affinity, ligand specificity orthologs, minimal effects on downstream signaling long-term fluorescence stability. By combining viral gene delivery fiber photometry-mediated measurements, demonstrate utility detection living mice. -mediated measurements indicate variability depending behavioral context physical condition an animal. will likely enable analysis physiological pathological processes.

Language: Английский

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Fluorescence Imaging of Neural Activity, Neurochemical Dynamics, and Drug-Specific Receptor Conformation with Genetically Encoded Sensors

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 273 - 294

Published: March 22, 2022

Recent advances in fluorescence imaging permit large-scale recording of neural activity and dynamics neurochemical release with unprecedented resolution behaving animals. Calcium highly optimized genetically encoded indicators provides a mesoscopic view from defined populations at cellular subcellular resolutions. Rigorously improved voltage sensors microscopy allow for robust spike populational neurons various brain regions. In addition, recent protein engineering efforts the past few years have led to development neurotransmitters neuromodulators. Here, we discuss applications these fluorescent reporting response behaviors different biological systems as well drug discovery. We also report simple model guide sensor selection optimization.

Language: Английский

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Local modulation by presynaptic receptors controls neuronal communication and behaviour

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(4), P. 191 - 203

Published: Feb. 28, 2022

Language: Английский

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Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 17, 2022

Abstract Endocannabinoid (eCB), 2 -arachidonoyl-glycerol (2-AG), the most abundant eCB in brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations 2-AG synthase diacylglycerol lipase β ( DAGLB ) to an early onset autosomal recessive Parkinsonism. is main human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, SN levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb nigral DANs substantially reduced impaired learning, particularly across-session learning. Conversely, pharmacological inhibition degradation increased levels, DAN activity dopamine release rescued learning deficits. Together, demonstrate that -deficiency contributes pathogenesis Parkinsonism, reveal importance DAGLB-mediated biosynthesis regulating neuronal release, suggest potential benefits augmentation alleviating

Language: Английский

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

Neuron, Journal Year: 2023, Volume and Issue: 111(10), P. 1564 - 1576.e6

Published: March 15, 2023

Language: Английский

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Planted Graphene Quantum Dots for Targeted, Enhanced Tumor Imaging and Long‐Term Visualization of Local Pharmacokinetics

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(15)

Published: Feb. 6, 2023

While photoluminescent graphene quantum dots (GQDs) have long been considered very suitable for bioimaging owing to their protein-like size, superhigh photostability and in vivo long-term biosafety, unique crucial applications remain unreachable. Herein, planted GQDs are presented as an excellent tool fluorescent, sustainable multimodality tumor various scenarios. The situ the poly(ethylene glycol) (PEG) layer of PEGylated nanoparticles via a bottom-up molecular approach obtain NPs-GQDs-PEG nanocomposite. show more than four times prolonged blood circulation 7-8 increased accumulation typical vivo. After accessible specificity modification, multifunctional provides targeted, multimodal imaging models vitro or Moreover, highly photostable enable long-term, real-time visualization local pharmacokinetics NPs Planting nanomedicine offers new strategy broad biomedical GQDs.

Language: Английский

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