In vivo autofluorescence lifetime imaging of the Drosophila brain captures metabolic shifts associated with memory formation DOI Open Access

Philémon Roussel,

Mingyi Zhou, Chiara Stringari

et al.

Published: March 31, 2025

Neuronal energy regulation is increasingly recognized as a critical factor underlying brain functions and their pathological alterations, yet the metabolic dynamics that accompany cognitive processes remain poorly understood. As label-free minimally invasive technique, fluorescence lifetime imaging (FLIM) of coenzymes NADH NADPH (collectively referred to NAD(P)H) offers possibility resolve cellular profiles with high spatial precision. However, NAD(P)H FLIM’s capacity detect subtle changes in neuronal metabolism associated cognition has not been demonstrated. In this study, we applied FLIM map Drosophila neurons vivo across multiple scales, focusing on primary centers for associative memory: mushroom bodies (MBs). At broad scale, obtained an overview signatures main tissue identified marked difference between neuropil cortex areas. finer our findings revealed notable heterogeneity basal distinct MB neuron subtypes. Measurements performed after olfactory learning also uncovered subtype-specific shift memory formation, demonstrating utility detecting physiology-driven linked function. These results establish promising framework studying cerebral vivo.

Language: Английский

Physiology of Astroglia DOI Open Access
Alexei Verkhratsky, Maiken Nedergaard

Physiological Reviews, Journal Year: 2017, Volume and Issue: 98(1), P. 239 - 389

Published: Dec. 24, 2017

Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide for homeostasis and defense the central nervous system (CNS). highly heterogeneous in morphological appearance; they express a multitude receptors, channels, membrane transporters. This complement underlies their remarkable adaptive plasticity defines functional maintenance CNS development aging. tightly integrated into networks act within context tissue; astrocytes control at all levels organization from molecular to whole organ.

Language: Английский

Citations

1329
A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain DOI Creative Commons
Kristofer Davie, Jasper Janssens,

Duygu Koldere

et al.

Cell, Journal Year: 2018, Volume and Issue: 174(4), P. 982 - 998.e20

Published: June 18, 2018

The diversity of cell types and regulatory states in the brain, how these change during aging, remains largely unknown. We present a single-cell transcriptome atlas entire adult Drosophila melanogaster brain sampled across its lifespan. Cell clustering identified 87 initial clusters that are further subclustered validated by targeted cell-sorting. Our data show high granularity identify wide range types. Gene network analyses using SCENIC revealed heterogeneity linked to energy consumption. During RNA content declines exponentially without affecting neuronal identity old brains. This covers nearly all cells normal provides tools study cellular alongside other mammalian datasets our unique analysis platform: SCope (http://scope.aertslab.org). These results, together with SCope, allow comprehensive exploration transcriptional an aging brain.

Language: Английский

Citations

788
A connectome of a learning and memory center in the adult Drosophila brain DOI Creative Commons
Shin-ya Takemura, Yoshinori Aso, Toshihide Hige

et al.

eLife, Journal Year: 2017, Volume and Issue: 6

Published: July 18, 2017

Understanding memory formation, storage and retrieval requires knowledge of the underlying neuronal circuits. In Drosophila, mushroom body (MB) is major site associative learning. We reconstructed morphologies synaptic connections all 983 neurons within three functional units, or compartments, that compose adult MB's α lobe, using a dataset isotropic 8 nm voxels collected by focused ion-beam milling scanning electron microscopy. found Kenyon cells (KCs), whose sparse activity encodes sensory information, each make multiple en passant synapses to MB output (MBONs) in compartment. Some MBONs have inputs from KCs, while others differentially sample modalities. Only 6% KC>MBON receive direct synapse dopaminergic neuron (DAN). identified two unanticipated classes synapses, KC>DAN DAN>MBON. DAN activation produces slow depolarization MBON these DAN>MBON can weaken recall.

Language: Английский

Citations

376
The connectome of the adult Drosophila mushroom body provides insights into function DOI Creative Commons
Feng Li, Jack Lindsey, Elizabeth C. Marin

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Dec. 14, 2020

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) well positioned for developing and testing such approach due to its conserved architecture, recently completed dense connectome, extensive prior experimental studies of roles learning, memory, activity regulation. Here, we identify new components MB circuit Drosophila, including visual input output neurons (MBONs) with direct connections descending neurons. We find unexpected structure sensory inputs, transfer information different modalities MBONs, modulation that dopaminergic (DANs). provide insights into circuitry used integrate outputs, between central complex inputs DANs, feedback MBONs. Our results a foundation further theoretical work.

Language: Английский

Citations

348
A gene-specific T2A-GAL4 library for Drosophila DOI Creative Commons
Pei-Tseng Lee, Jonathan Zirin, Oguz Kanca

et al.

eLife, Journal Year: 2018, Volume and Issue: 7

Published: March 22, 2018

We generated a library of ~1000 Drosophila stocks in which we inserted construct the intron genes allowing expression GAL4 under control endogenous promoters while arresting transcription with polyadenylation signal 3' GAL4. This allows numerous applications. First, ~90% insertions essential cause severe loss-of-function phenotype, an effective way to mutagenize genes. Interestingly, 12/14 chromosomes engineered through CRISPR do not carry second-site lethal mutations. Second, 26/36 (70%) tested are rescued single UAS-cDNA construct. Third, phenotypes associated many can be reverted by excision UAS-flippase. Fourth, driven UAS-GFP/RFP reports tissue and cell-type specificity gene high sensitivity. report hundreds previously reported. Finally, cassettes replaced GFP or any DNA. These comprise powerful resource for assessing function.

Language: Английский

Citations

293
Questions and (some) answers on reactive astrocytes DOI
Carole Escartin,

Océane Guillemaud,

María-Angeles Carrillo-de Sauvage

et al.

Glia, Journal Year: 2019, Volume and Issue: 67(12), P. 2221 - 2247

Published: Aug. 19, 2019

Abstract Astrocytes are key cellular partners for neurons in the central nervous system. react to virtually all types of pathological alterations brain homeostasis by significant morphological and molecular changes. This response was classically viewed as stereotypical is called astrogliosis or astrocyte reactivity. It long considered a nonspecific, secondary reaction conditions, offering no clues on disease‐causing mechanisms with little therapeutic value. However, many studies over last 30 years have underlined crucial active roles played astrocytes physiology, ranging from metabolic support, synapse maturation, pruning fine regulation synaptic transmission. prompted researchers explore how these new functions were changed disease, they reported them (sometimes beneficial, mostly deleterious). More recently, cell‐specific transcriptomics revealed that undergo massive changes gene expression when become reactive. observation further stressed reactive may be very different normal, nonreactive could influence disease outcomes. To make picture even more complex, both normal shown molecularly functionally heterogeneous. Very known about specific each subtype play contexts. In this review, we interrogated field identify discuss points consensus controversies astrocytes, starting their name. We then present emerging knowledge cells future challenges field.

Language: Английский

Citations

242
Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features DOI Creative Commons
Νικόλαος Κωνσταντινίδης, Katarina Kapuralin, Chaimaa Fadil

et al.

Cell, Journal Year: 2018, Volume and Issue: 174(3), P. 622 - 635.e13

Published: June 18, 2018

Language: Английский

Citations

229
Stratification of astrocytes in healthy and diseased brain DOI
Alexei Verkhratsky, Robert Zorec, Vladimir Parpura

et al.

Brain Pathology, Journal Year: 2017, Volume and Issue: 27(5), P. 629 - 644

Published: Aug. 13, 2017

Abstract Astrocytes, a subtype of glial cells, come in variety forms and functions. However, overarching role these cell is the homeostasis brain, be that regulation ions, neurotransmitters, metabolism or neuronal synaptic networks. Loss represents underlying cause all brain disorders. Thus, astrocytes are likely involved most if not pathologies. We tabulate astroglial homeostatic functions along with pathological condition arise from dysfunction cells. Classification presented emphasis on evolutionary trails, morphological appearance numerical preponderance. note that, even though mammalian species share some common features, human appear to largest complex studied thus far. It then an imperative develop humanized models study pathologies, which perhaps abundantly clear case glioblastoma multiforme.

Language: Английский

Citations

215
Neuronal wiring diagram of an adult brain DOI Creative Commons
Sven Dorkenwald, Arie Matsliah, Amy Sterling

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8032), P. 124 - 138

Published: Oct. 2, 2024

Language: Английский

Citations

147
Neuronal wiring diagram of an adult brain DOI Creative Commons
Sven Dorkenwald, Arie Matsliah, Amy Sterling

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 30, 2023

Abstract Connections between neurons can be mapped by acquiring and analyzing electron microscopic (EM) brain images. In recent years, this approach has been applied to chunks of brains reconstruct local connectivity maps that are highly informative, yet inadequate for understanding function more globally. Here, we present the first neuronal wiring diagram a whole adult brain, containing 5×10 7 chemical synapses ∼130,000 reconstructed from female Drosophila melanogaster . The resource also incorporates annotations cell classes types, nerves, hemilineages, predictions neurotransmitter identities. Data products available download, programmatic access, interactive browsing made interoperable with other fly data resources. We show how derive projectome, map projections regions, connectome. demonstrate tracing synaptic pathways analysis information flow inputs (sensory ascending neurons) outputs (motor, endocrine, descending neurons), across both hemispheres, central optic lobes. Tracing subset photoreceptors all way motor illustrates structure uncover putative circuit mechanisms underlying sensorimotor behaviors. technologies open ecosystem FlyWire Consortium set stage future large-scale connectome projects in species.

Language: Английский

Citations

135