Conserved neural circuit structure across Drosophila larval development revealed by comparative connectomics

Gerhard, Stephan; Andrade, Ingrid; Fetter, Richard D.; Cardona, Albert; Schneider-Mizell, Casey M

doi:10.7554/elife.29089

Cited by 99 publications

(103 citation statements)

References 56 publications

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“…Connectivity matrices have now been reported more recently for other parts of the Drosophila brain, in both the adult (Takemura et al, 2013(Takemura et al, , 2015(Takemura et al, , 2017a and larva (e.g. Schneider-Mizell et al, 2016;Gerhard et al, 2017).…”

Section: Em Plays An Essential Rolementioning

confidence: 97%

Of what use is connectomics? A personal perspective on theDrosophilaconnectome

Meinertzhagen

2018

Journal of Experimental Biology

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The brain is a network of neurons and its biological output is behaviour. This is an exciting age, with a growing acknowledgement that the comprehensive compilation of synaptic circuits densely reconstructed in the brains of model species is now both technologically feasible and a scientifically enabling possibility in neurobiology, much as 30 years ago genomics was in molecular biology and genetics. Implemented by huge advances in electron microscope technology, especially focused ion beam-scanning electron microscope (FIB-SEM) milling (see Glossary), image capture and alignment, and computer-aided reconstruction of neuron morphologies, enormous progress has been made in the last decade in the detailed knowledge of the actual synaptic circuits formed by real neurons, in various brain regions of the fly It is useful to distinguish synaptic pathways that are major, with 100 or more presynaptic contacts, from those that are minor, with fewer than about 10; most neurites are both presynaptic and postsynaptic, and all synaptic sites have multiple postsynaptic dendrites. Work on has spearheaded these advances because cell numbers are manageable, and neuron classes are morphologically discrete and genetically identifiable, many confirmed by reporters. Recent advances are destined within the next few years to reveal the complete connectome in an adult fly, paralleling advances in the larval brain that offer the same prospect possibly within an even shorter time frame. The final amendment and validation of segmented bodies by human proof-readers remains the most time-consuming step, however. The value of a complete connectome in is that, by targeting to specific neurons transgenes that either silence or activate morphologically identified circuits, and then identifying the resulting behavioural outcome, we can determine the causal mechanism for behaviour from its loss or gain. More importantly, the connectome reveals hitherto unsuspected pathways, leading us to seek novel behaviours for these. Circuit information will eventually be required to understand how differences between brains underlie differences in behaviour, and especially to herald yet more advanced connectomic strategies for the vertebrate brain, with an eventual prospect of understanding cognitive disorders having a connectomic basis. Connectomes also help us to identify common synaptic circuits in different species and thus to reveal an evolutionary progression in candidate pathways.

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Section: Em Plays An Essential Rolementioning

confidence: 97%

Of what use is connectomics? A personal perspective on theDrosophilaconnectome

Meinertzhagen

2018

Journal of Experimental Biology

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“…Serial-section electron microscopy (EM) allows reconstruction of neural circuits with synapse resolution [14][15][16][17][18][19][20] , but low throughput makes it difficult to compare whole brain samples and comprehensively assess plasticity. EM has been applied to assess wiring differences between species 21 , sexes 22 , genotypes 23 , and ages 4,24 . But previous studies mapped partial circuits or few samples.…”

Section: Introductionmentioning

confidence: 99%

Connectomes across development reveal principles of brain maturation

Witvliet

Mulcahy

Mitchell

et al. 2020

Preprint

160

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From birth to adulthood, an animal's nervous system changes as its body grows and its behaviours mature. However, the extent of circuit remodelling across the connectome is poorly understood. Here, we used serial-section electron microscopy to reconstruct the brain of eight isogenic C. elegans individuals at different ages to learn how an entire wiring diagram changes with maturation. We found that the overall geometry of the nervous system is preserved from birth to adulthood, establishing a constant scaffold upon which synaptic change is built. We observed substantial connectivity differences among individuals that make each brain partly unique. We also observed developmental connectivity changes that are consistent between animals but different among neurons, altering the strengths of existing connections and creating additional connections. Collective synaptic changes alter information processing of the brain. Across maturation, the decision-making circuitry is maintained whereas sensory and motor pathways are substantially remodelled, and the brain becomes progressively more modular and feedforward. These synaptic changes reveal principles that underlie brain maturation.Witvliet et al. | bioRχiv | May 21, 2020 | 1-26

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“…We also show that dendrite elaboration occurs much later than axon extension in the U motor neurons. The observation that axon outgrowth precedes dendrite outgrowth has been widely reported (Gerhard et al, 2017;Mason, 1983;Mumm et al, 2006;Ramon y Cajal, 1909), although the mechanism that sets the time of axon or dendrite outgrowth is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila

Seroka

Doe

2019

Development

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The generation of neuronal diversity is essential for circuit formation and behavior. Morphological differences in sequentially born neurons could be due to intrinsic molecular identity specified by temporal transcription factors (henceforth called intrinsic temporal identity) or due to changing extrinsic cues. Here, we have used the Drosophila NB7-1 lineage to address this issue. NB7-1 generates the U1-U5 motor neurons sequentially; each has a distinct intrinsic temporal identity due to inheritance of different temporal transcription factors at its time of birth. We show that the U1-U5 neurons project axons sequentially, followed by sequential dendrite extension. We misexpressed the earliest temporal transcription factor, Hunchback, to create 'ectopic' U1 neurons with an early intrinsic temporal identity but later birth-order. These ectopic U1 neurons have axon muscle targeting and dendrite neuropil targeting that are consistent with U1 intrinsic temporal identity, rather than with their time of birth or differentiation. We conclude that intrinsic temporal identity plays a major role in establishing both motor axon muscle targeting and dendritic arbor targeting, which are required for proper motor circuit development.

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Conserved neural circuit structure across Drosophila larval development revealed by comparative connectomics

Cited by 99 publications

References 56 publications

Of what use is connectomics? A personal perspective on theDrosophilaconnectome

Of what use is connectomics? A personal perspective on theDrosophilaconnectome

Connectomes across development reveal principles of brain maturation

The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila

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