The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles DOI Creative Commons
Verena M. Straub, Benjámin Barti, Sebastian T. Tandar

et al.

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

Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators DOI
Zhaofa Wu, Dayu Lin, Yulong Li

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(5), P. 257 - 274

Published: March 31, 2022

Language: Английский

Citations

156
Fluorescence imaging of large-scale neural ensemble dynamics DOI Creative Commons
Tony Hyun Kim, Mark J. Schnitzer

Cell, Journal Year: 2022, Volume and Issue: 185(1), P. 9 - 41

Published: Jan. 1, 2022

Language: Английский

Citations

116
Anandamide and other N-acylethanolamines: A class of signaling lipids with therapeutic opportunities DOI Creative Commons
Elliot D. Mock, Berend Gagestein, Mario van der Stelt

et al.

Progress in Lipid Research, Journal Year: 2022, Volume and Issue: 89, P. 101194 - 101194

Published: Sept. 20, 2022

N-acylethanolamines (NAEs), including N-palmitoylethanolamine (PEA), N-oleoylethanolamine (OEA), N-arachidonoylethanolamine (AEA, anandamide), N-docosahexaenoylethanolamine (DHEA, synaptamide) and their oxygenated metabolites are a lipid messenger family with numerous functions in health disease, inflammation, anxiety energy metabolism. The NAEs exert signaling role through activation of various G protein-coupled receptors (cannabinoid CB1 CB2 receptors, GPR55, GPR110, GPR119), ion channels (TRPV1) nuclear (PPAR-α PPAR-γ) the brain periphery. biological NAEs, such as prostamides, hydroxylated anandamide DHEA derivatives, less studied. Evidence is accumulating that oxidative may be aberrantly regulated or associated disease severity obesity, metabolic syndrome, cancer, neuroinflammation liver cirrhosis. Here, we comprehensively review NAE biosynthesis degradation, metabolism by lipoxygenases, cyclooxygenases cytochrome P450s these lipids. We discuss latest findings therapeutic potential modulating endogenous levels inhibition which currently under clinical evaluation for neuropsychiatric disorders. also highlight an emerging topic opportunities endocannabinoid signaling.

Language: Английский

Citations

87
A genetically encoded sensor measures temporal oxytocin release from different neuronal compartments DOI
Tongrui Qian, Huan Wang, Peng Wang

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(7), P. 944 - 957

Published: Jan. 2, 2023

Language: Английский

Citations

79
THC and CBD: Similarities and differences between siblings DOI Creative Commons
Nephi Stella

Neuron, Journal Year: 2023, Volume and Issue: 111(3), P. 302 - 327

Published: Jan. 12, 2023

Citations

58
Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo DOI
Yizhou Zhuo, Bin Luo, Xinyang Yi

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 21(4), P. 680 - 691

Published: Nov. 30, 2023

Language: Английский

Citations

56
Lights, fiber, action! A primer on in vivo fiber photometry DOI Creative Commons
Eleanor H. Simpson, Thomas Akam, Tommaso Patriarchi

et al.

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

Citations

51
Sensitive multicolor indicators for monitoring norepinephrine in vivo DOI
Zacharoula Kagiampaki, Valentin Lu Rohner, Cedric Kiss

et al.

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

Published: July 20, 2023

Language: Английский

Citations

45
Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo DOI
Fei Deng, Jinxia Wan,

Guochuan Li

et al.

Nature Methods, Journal Year: 2024, Volume and Issue: 21(4), P. 692 - 702

Published: March 5, 2024

Language: Английский

Citations

25
Mechanisms of neuromodulatory volume transmission DOI Creative Commons
Özge Demet Özçete, Aditi Banerjee, Pascal S. Kaeser

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(11), P. 3680 - 3693

Published: May 24, 2024

Abstract A wealth of neuromodulatory transmitters regulate synaptic circuits in the brain. Their mode signaling, often called volume transmission, differs from classical transmission important ways. In vesicles rapidly fuse response to action potentials and release their transmitter content. The are then sensed by nearby receptors on select target cells with minimal delay. Signal is restricted contacts typically occurs within ~1 ms. Volume doesn’t rely contact sites main monoamines neuropeptides, neuromodulators It less precise than underlying molecular mechanisms spatiotemporal scales not well understood. Here, we review literature raise scientific questions that should be addressed years ahead. We define five domains which systems can differ one another. These (1) innervation patterns firing properties, (2) synthesis loading into different types vesicles, (3) architecture distribution sites, (4) diffusion, degradation, reuptake, (5) receptor positioning cells. discuss these for dopamine, a well-studied monoamine, compare dopamine norepinephrine serotonin. include assessments neuropeptide signaling central acetylcholine transmission. Through this review, provide cellular framework This mechanistic knowledge essential how control behavior health disease understand they modulated medical treatments drugs abuse.

Language: Английский

Citations

22