Next-generation GRAB sensors for monitoring dopaminergic activity in vivo

Nature Methods, Год журнала: 2020, Номер 17(11), С. 1156 - 1166

Опубликована: Окт. 21, 2020

Язык: Английский

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The emergence and influence of internal states

Neuron, Год журнала: 2022, Номер 110(16), С. 2545 - 2570

Опубликована: Май 27, 2022

Язык: Английский

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A transcriptomic taxonomy of Drosophila circadian neurons around the clock

eLife, Год журнала: 2021, Номер 10

Опубликована: Янв. 13, 2021

Many different functions are regulated by circadian rhythms, including those orchestrated discrete clock neurons within animal brains. To comprehensively characterize and assign cell identity to the 75 pairs of Drosophila neurons, we optimized a single-cell RNA sequencing method assayed neuron gene expression at times day. The data identify least 17 categories with striking spatial regulation expression. Transcription factor is prominent likely contributes robust oscillation many transcripts, that encode cell-surface proteins previously shown be important for recognition synapse formation during development. other clock-regulated genes also constitute an resource future mechanistic functional studies between and/or temporal signaling circuits elsewhere in fly brain.

Язык: Английский

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Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster

Cell, Год журнала: 2024, Номер 187(10), С. 2574 - 2594.e23

Опубликована: Май 1, 2024

High-resolution electron microscopy of nervous systems has enabled the reconstruction synaptic connectomes. However, we do not know sign for each connection (i.e., whether a is excitatory or inhibitory), which implied by released transmitter. We demonstrate that artificial neural networks can predict transmitter types presynapses from micrographs: network trained to six transmitters (acetylcholine, glutamate, GABA, serotonin, dopamine, octopamine) achieves an accuracy 87% individual synapses, 94% neurons, and 91% known cell across D. melanogaster whole brain. visualize ultrastructural features used prediction, discovering subtle but significant differences between phenotypes. also analyze distributions brain find neurons develop together largely express only one fast-acting GABA). hope our publicly available predictions act as accelerant neuroscientific hypothesis generation fly.

Язык: Английский

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

Cell Reports, Год журнала: 2023, Номер 42(9), С. 113058 - 113058

Опубликована: Авг. 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.

Язык: 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, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 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.

Язык: Английский

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Transcriptional complexity in the insect central complex: single nuclei RNA-sequencing of adult brain neurons derived from type 2 neuroblasts

Опубликована: Фев. 27, 2025

In both invertebrates such as Drosophila and vertebrates mouse or human, the brain contains most diverse population of cell types any tissue. It is generally accepted that transcriptional diversity an early step in generating neuronal glial diversity, followed by establishment a unique gene expression profile determines morphology, connectivity, function. , there are two neural stem cells, called Type 1 (T1) 2 (T2) neuroblasts. contrast to T1 neuroblasts, T2 neuroblasts generate intermediate progenitors (INPs) expand number types. The T2-derived neurons contributes large portion central complex (CX), conserved region plays role sensorimotor integration. Recent work has revealed much connectome CX, but how this assembled remains unclear. Mapping derived from necessary linking assembly adult brain. Here we perform single nuclei RNA sequencing neuroblast-derived glia. We identify clusters containing all known classes glia, male/female enriched, 161 neuron-specific clusters. map neurotransmitter neuropeptide transcription factor combinatorial codes for each cluster (presumptive neuron subtype). This directs functional studies determine whether code specifies distinct type within CX. several columnar subtypes (NPF+ AstA+) closely related Our data support hypothesis represents one few subtypes.

Язык: Английский

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Neurochemical Organization of the Drosophila Brain Visualized by Endogenously Tagged Neurotransmitter Receptors

Cell Reports, Год журнала: 2020, Номер 30(1), С. 284 - 297.e5

Опубликована: Янв. 1, 2020

Neurotransmitters often have multiple receptors that induce distinct responses in receiving cells. Expression and localization of neurotransmitter individual neurons are therefore critical for understanding the operation neural circuits. Here we describe a comprehensive library reporter strains which convertible T2A-GAL4 cassette is inserted into endogenous receptor genes Drosophila. Using this library, profile expression 75 brain. Cluster analysis reveals neurochemical segmentation brain, distinguishing higher brain centers from rest. By recombinase-mediated exchange, convert split-GFP Tango to visualize subcellular activation dopamine specific cell types. This striking differences their localization, may underlie cellular different behavioral contexts. Our resources thus provide versatile toolkit dissecting organization function systems fly

Язык: Английский

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The Cellular Diversity and Transcription Factor Code of Drosophila Enteroendocrine Cells

Cell Reports, Год журнала: 2019, Номер 29(12), С. 4172 - 4185.e5

Опубликована: Дек. 1, 2019

Enteroendocrine cells (EEs) in the intestinal epithelium have important endocrine functions, yet this cell lineage exhibits great local and regional variations that hampered detailed characterization of EE subtypes. Through single-cell RNA-sequencing analysis, combined with a collection peptide hormone receptor knockin strains, here we provide comprehensive analysis cellular diversity, spatial distribution, transcription factor (TF) code EEs adult Drosophila midgut. We identify 10 major subtypes totally produced approximately 14 different classes peptides. Each on average co-produces 2–5 Functional screen subtype-enriched TFs suggests combinatorial TF controls diversity; class-specific Mirr Ptx1 respectively define two EEs, such as Esg, Drm, Exex, Fer1 further identity. Our data should greatly facilitate modeling differentiation function.

Язык: Английский

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The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Авг. 10, 2021

Abstract The enteroendocrine cell (EEC)-derived incretins play a pivotal role in regulating the secretion of glucagon and insulins mammals. Although glucagon-like insulin-like hormones have been found across animal phyla, incretin-like EEC-derived not yet characterised invertebrates. Here, we show that midgut-derived hormone, neuropeptide F (NPF), acts as sugar-responsive, hormone fruit fly, Drosophila melanogaster . Secreted NPF is received by receptor corpora cardiaca insulin-producing cells. NPF-NPFR signalling resulted suppression production enhancement peptide secretion, eventually promoting lipid anabolism. Similar to loss incretin function mammals, midgut led significant metabolic dysfunction, accompanied lipodystrophy, hyperphagia, hypoglycaemia. These results suggest regulate sugar-dependent metabolism through only mammals but also insects.

Язык: Английский

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