Physiology of Astroglia

Physiological Reviews, Год журнала: 2017, Номер 98(1), С. 239 - 389

Опубликована: Дек. 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.

Язык: Английский

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A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain

Cell, Год журнала: 2018, Номер 174(4), С. 982 - 998.e20

Опубликована: Июнь 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.

Язык: Английский

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A connectome of a learning and memory center in the adult Drosophila brain

eLife, Год журнала: 2017, Номер 6

Опубликована: Июль 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.

Язык: Английский

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The connectome of the adult Drosophila mushroom body provides insights into function

eLife, Год журнала: 2020, Номер 9

Опубликована: Дек. 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.

Язык: Английский

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A gene-specific T2A-GAL4 library for Drosophila

eLife, Год журнала: 2018, Номер 7

Опубликована: Март 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.

Язык: Английский

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Questions and (some) answers on reactive astrocytes

Glia, Год журнала: 2019, Номер 67(12), С. 2221 - 2247

Опубликована: Авг. 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.

Язык: Английский

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Phenotypic Convergence: Distinct Transcription Factors Regulate Common Terminal Features

Cell, Год журнала: 2018, Номер 174(3), С. 622 - 635.e13

Опубликована: Июнь 18, 2018

Язык: Английский

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Stratification of astrocytes in healthy and diseased brain

Brain Pathology, Год журнала: 2017, Номер 27(5), С. 629 - 644

Опубликована: Авг. 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.

Язык: Английский

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Drosophila glia: Few cell types and many conserved functions

Glia, Год журнала: 2018, Номер 67(1), С. 5 - 26

Опубликована: Ноя. 15, 2018

Abstract Glial cells constitute without any dispute an essential element in providing efficiently operating nervous system. Work many labs over the last decades has demonstrated that neuronal function, from action potential generation to its propagation, eliciting synaptic responses subsequent postsynaptic integration, is evolutionarily highly conserved. Likewise, biology of glial appears conserved core elements and therefore, a deeper understanding expected benefit analyzing model organisms such as Drosophila melanogaster . particularly well suited for studying since fly system only limited number exists, which can be individually identified based on position set molecular markers. In combination with well‐known genetic tool box unprecedented level analysis feasible, not help identify novel molecules principles governing cell function but also will better understand functions first mammalian Here we review current knowledge glia spark interest using this analyze complex traits future.

Язык: Английский

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Neuronal wiring diagram of an adult brain

Nature, Год журнала: 2024, Номер 634(8032), С. 124 - 138

Опубликована: Окт. 2, 2024

Язык: Английский

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