A Pipeline for Volume Electron Microscopy of the Caenorhabditis elegans Nervous System

Mulcahy, Ben; Witvliet, Daniel; Holmyard, Douglas; Mitchell, James K.; Chisholm, Andrew; Meirovitch, Yaron; Samuel, Aravinthan D. T.; Zhen, Mei

doi:10.3389/fncir.2018.00094

Cited by 38 publications

(36 citation statements)

References 112 publications

(154 reference statements)

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“…They were subsequently frozen using a Leica EM PACT 2 high-pressure freezer and stored in liquid nitrogen. Freeze-substitution was performed in a Leica EM AFS2 unit in flat-bottomed BEEM capsules using methods modified from those previously published [ 79 ]. Samples were incubated at − 90 °C for 48 h in 0.1% tannic acid and 0.5% glutaraldehyde.…”

Section: Methodsmentioning

confidence: 99%

Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans

Byrne

Soh

Chandhok

et al. 2019

Cell. Mol. Life Sci.

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Mitochondria are essential components of eukaryotic cells, carrying out critical physiological processes that include energy production and calcium buffering. Consequently, mitochondrial dysfunction is associated with a range of human diseases. Fundamental to their function is the ability to transition through fission and fusion states, which is regulated by several GTPases. Here, we have developed new methods for the non-subjective quantification of mitochondrial morphology in muscle and neuronal cells of Caenorhabditis elegans . Using these techniques, we uncover surprising tissue-specific differences in mitochondrial morphology when fusion or fission proteins are absent. From ultrastructural analysis, we reveal a novel role for the fusion protein FZO-1/mitofusin 2 in regulating the structure of the inner mitochondrial membrane. Moreover, we have determined the influence of the individual mitochondrial fission (DRP-1/DRP1) and fusion (FZO-1/mitofusin 1,2; EAT-3/OPA1) proteins on animal behaviour and lifespan. We show that loss of these mitochondrial fusion or fission regulators induced age-dependent and progressive deficits in animal movement, as well as in muscle and neuronal function. Our results reveal that disruption of fusion induces more profound defects than lack of fission on animal behaviour and tissue function, and imply that while fusion is required throughout life, fission is more important later in life likely to combat ageing-associated stressors. Furthermore, our data demonstrate that mitochondrial function is not strictly dependent on morphology, with no correlation found between morphological changes and behavioural defects. Surprisingly, we find that disruption of either mitochondrial fission or fusion significantly reduces median lifespan, but maximal lifespan is unchanged, demonstrating that mitochondrial dynamics play an important role in limiting variance in longevity across isogenic populations. Overall, our study provides important new insights into the central role of mitochondrial dynamics in maintaining organismal health. Electronic supplementary material The online version of this article (10.1007/s00018-019-03024-5) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans

Byrne

Soh

Chandhok

et al. 2019

Cell. Mol. Life Sci.

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“…Over the past century, scientists working on invertebrate animal models have unraveled the cellular atlas, especially in C. elegans, [122,123] how cells interact across a network of brain regions, and which cell types encode the various sensory inputs. [124] Now, we also have models of the mechanisms by which environmental cues are combined with goal-driven information to generate a spatial representation.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Prominent Inhibitory Projections Guide Sensorimotor Computation: An Invertebrate Perspective

Hughes

Celikel

2019

BioEssays

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From single-cell organisms to complex neural networks, all evolved to provide control solutions to generate context-and goal-specific actions. Neural circuits performing sensorimotor computation to drive navigation employ inhibitory control as a gating mechanism as they hierarchically transform (multi)sensory information into motor actions. Here, the focus is on this literature to critically discuss the proposition that prominent inhibitory projections form sensorimotor circuits. After reviewing the neural circuits of navigation across various invertebrate species, it is argued that with increased neural circuit complexity and the emergence of parallel computations, inhibitory circuits acquire new functions. The contribution of inhibitory neurotransmission for navigation goes beyond shaping the communication that drives motor neurons, and instead includes encoding of emergent sensorimotor representations. A mechanistic understanding of the neural circuits performing sensorimotor computations in invertebrates will unravel the minimum circuit requirements driving adaptive navigation.

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“…Over the past century, scientists working on invertebrate animal models have unravelled the cellular atlas, especially in C. elegans [113,114] , how cells interact across a network of brain regions and which cell types encode the various sensory inputs [115] . Now, we also have models of the mechanisms by which environmental cues are combined with goal-driven information to generate a spatial representation [100,103,104] .…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Prominent Inhibitory Projections Guide Sensorimotor Computation: An Invertebrate Perspective

Hughes

Celikel

2019

Preprint

View full text Add to dashboard Cite

From single-cell organisms to complex neural networks, all evolved to provide control solutions to generate context and goal-specific actions. Neural circuits performing sensorimotor computation to drive navigation employ inhibitory control as a gating mechanism, as they hierarchically transform (multi)sensory information into motor actions. Here, we focus on this literature to critically discuss the proposition that prominent inhibitory projections form sensorimotor circuits. After reviewing the neural circuits of navigation across various invertebrate species, we argue that with increased neural circuit complexity and the emergence of parallel computations inhibitory circuits acquire new functions. The contribution of inhibitory neurotransmission for navigation goes beyond shaping the communication that drives motor neurons, instead, include encoding of emergent sensorimotor representations. A mechanistic understanding of the neural circuits performing sensorimotor computations in invertebrates will unravel the minimum circuit requirements driving adaptive navigation.

show abstract

A Pipeline for Volume Electron Microscopy of the Caenorhabditis elegans Nervous System

Cited by 38 publications

References 112 publications

Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans

Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans

Prominent Inhibitory Projections Guide Sensorimotor Computation: An Invertebrate Perspective

Prominent Inhibitory Projections Guide Sensorimotor Computation: An Invertebrate Perspective

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