The neuropeptidergic connectome of C. elegans

Neuron, Год журнала: 2023, Номер 111(22), С. 3570 - 3589.e5

Опубликована: Ноя. 1, 2023

Efforts are ongoing to map synaptic wiring diagrams, or connectomes, understand the neural basis of brain function. However, chemical synapses represent only one type functionally important neuronal connection; in particular, extrasynaptic, "wireless" signaling by neuropeptides is widespread and plays essential roles all nervous systems. By integrating single-cell anatomical gene-expression datasets with biochemical analysis receptor-ligand interactions, we have generated a draft connectome neuropeptide C. elegans system. This network characterized high connection density, extended cascades, autocrine foci, decentralized topology, large, highly interconnected core containing three constituent communities sharing similar patterns input connectivity. Intriguingly, several key hubs little-studied neurons that appear specialized for peptidergic neuromodulation. We anticipate neuropeptidergic will serve as prototype how networks neuromodulatory organized.

Язык: Английский

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Hormone-mediated neural remodeling orchestrates parenting onset during pregnancy

Science, Год журнала: 2023, Номер 382(6666), С. 76 - 81

Опубликована: Окт. 6, 2023

During pregnancy, physiological adaptations prepare the female body for challenges of motherhood. Becoming a parent also requires behavioral adaptations. Such can occur as early during but how pregnancy hormones remodel parenting circuits to instruct preparatory changes remains unknown. We found that action estradiol and progesterone on galanin (Gal)–expressing neurons in mouse medial preoptic area (MPOA) is critical pregnancy-induced parental behavior. Whereas silences MPOA Gal paradoxically increases their excitability, permanently rewires this circuit node by promoting dendritic spine formation recruitment excitatory synaptic inputs. This -specific neural remodeling sparsens population activity vivo results persistently stronger, more selective responses pup stimuli. Pregnancy thus anticipation future need.

Язык: Английский

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Benchtop mesoSPIM: a next-generation open-source light-sheet microscope for cleared samples

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 27, 2024

Abstract In 2015, we launched the mesoSPIM initiative, an open-source project for making light-sheet microscopy of large cleared tissues more accessible. Meanwhile, demand imaging larger samples at higher speed and resolution has increased, requiring major improvements in capabilities such microscopes. Here, introduce next-generation (“Benchtop”) with a significantly increased field view, improved resolution, throughput, affordable cost, simpler assembly compared to original version. We develop optical method testing detection objectives that enables us select optimal large-sensor cameras. The achieves high spatial (1.5 µm laterally, 3.3 axially) across entire magnification up 20×, supports sample sizes ranging from sub-mm several centimeters while being compatible multiple clearing techniques. microscope serves broad range applications neuroscience, developmental biology, pathology, even physics.

Язык: Английский

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Virtual reality-empowered deep-learning analysis of brain cells

Nature Methods, Год журнала: 2024, Номер 21(7), С. 1306 - 1315

Опубликована: Апрель 22, 2024

Abstract Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos + markers neuronal activity cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our available user-friendly Docker container that runs with standalone Fiji plugin. features comprehensive toolkit visualization and can be customized other cell types interest, did here microglia somata, using dataset-specific training. We applied investigate cancer-related brain activity, unveiling an activation pattern distinguishes weight-stable cancer from cancers associated weight loss. Overall, robust tool does not require advanced coding skills analyze imaging health disease.

Язык: Английский

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Midbrain ghrelin receptor signalling regulates binge drinking in a sex specific manner

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 15, 2025

Abstract Risky drinking rates are rising, particularly in women, yet sex as a biological variable has only recently gained traction. The centrally projecting Edinger-Westphal (EWcp) nucleus emerged key regulator of alcohol consumption. Here we found that EWcp peptidergic cells reduce binge specifically female mice. We show this effect is mediated by the ghrelin receptor (GHSR), with inhibition blocking ghrelin-induced and Ghsr knockdown , but not glutamatergic or ventral tegmental area cells, reducing females, independent circulating hormones. Female mice showed higher expression, neurons were more sensitive to ghrelin. Moreover, intra-EWcp delivery GHSR inverse agonist antagonist reduced drinking, suggesting direct actions These findings highlight critical mediator excessive consumption via mice, offering insights into system’s role

Язык: Английский

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Peptidergic and functional delineation of the Edinger-Westphal nucleus

Cell Reports, Год журнала: 2023, Номер 42(8), С. 112992 - 112992

Опубликована: Авг. 1, 2023

Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower-acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether neurons solely peptides exist. Our fluorescence situ hybridization, genetically targeted electron microscopy, electrophysiological characterization suggest most of non-cholinergic, centrally projecting Edinger-Westphal nucleus mice obligately peptidergic. We further show, using anterograde projection mapping, monosynaptic retrograde tracing, angled-tip fiber photometry, chemogenetic modulation ablation conjunction with canonical assays for anxiety, this population activates response to loss motor control promotes anxiety responses. Together, these findings elucidate an integrative, ethologically relevant role functionally align periaqueductal gray, where resides. This work advances our understanding provides a framework future investigations systems.

Язык: Английский

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A Sleep‐Specific Midbrain Target for Sevoflurane Anesthesia

Advanced Science, Год журнала: 2023, Номер 10(15)

Опубликована: Март 24, 2023

Sevoflurane has been the most widely used inhaled anesthetics with a favorable recovery profile; however, precise mechanisms underlying its anesthetic action are still not completely understood. Here authors show that sevoflurane activates cluster of urocortin 1 (UCN1

Язык: Английский

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Neural and behavioral plasticity across the female reproductive cycle

Trends in Endocrinology and Metabolism, Год журнала: 2022, Номер 33(11), С. 769 - 785

Опубликована: Окт. 14, 2022

Язык: Английский

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Imprinted genes and the manipulation of parenting in mammals

Nature Reviews Genetics, Год журнала: 2023, Номер 24(11), С. 783 - 796

Опубликована: Сен. 15, 2023

Язык: Английский

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Functionally active TRPA1 ion channel is downregulated in peptidergic neurons of the Edinger-Westphal nucleus upon acute alcohol exposure

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 10

Опубликована: Янв. 10, 2023

Introduction: The centrally projecting Edinger-Westphal nucleus (EWcp) contributes to the control of alcohol consumption by its urocortin 1 (UCN1) and cocaine- amphetamine-regulated transcript (CART) co-expressing peptidergic neurons. Our group recently showed that urocortinergic EWcp is primary seat central nervous system transient receptor potential ankyrin (TRPA1) cation channel mRNA expression. Here, we hypothesized metabolites, pass through blood-brain barrier, may influence function cells in activating TRPA1 ion channels. We aimed examine functional activity possible role a mouse model acute exposure. Methods: Electrophysiological measurements were performed on brain slices C57BL/6J male mice containing prove using selective, potent, covalent agonist JT010. Male knockout (KO) wildtype (WT) compared with each other morphological studies upon treatment. In both genotypes, half animals was treated intraperitoneally g/kg 6% ethanol vs. physiological saline-injected controls. Transcardial perfusion 2 h after area, FOS immunohistochemistry assess neuronal activation. TRPA1, CART, expression as well CART peptide content semi-quantified RNAscope situ hybridization combined immunofluorescence. Results: JT010 activated channels slices. Alcohol treatment resulted significant activation genotypes. decreased Trpa1 WT mice. assessment immunoreactivity revealed lower basal KO WTs. affected genotype-dependently alcohol: WTs while it increased exposure influenced neither nor EWcp/CART content. Conclusion: proved presence receptors neurons EWcp. Decreased treatment, associated reduced suggesting this contribute regulation release.

Язык: Английский

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