BAcTrace, a tool for retrograde tracing of neuronal circuits in Drosophila

Cachero, Sebastian; Gkantia, Marina; Bates, Alexander Shakeel; Frechter, Shahar; Blackie, Laura; McCarthy, Amy; Sutcliffe, Ben; Strano, Alessio; Aso, Yoshinori; Jefferis, Gregory

doi:10.1038/s41592-020-00989-1

Cited by 37 publications

(41 citation statements)

References 55 publications

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“…Structural connectivity from the hemibrain does not necessarily capture functional connections assayed by physiology. Encouragingly, however, recent work with a retrograde genetic system for finding neurons that input onto genetically targetable cells found 6/7 glomerular connections to LHPD2a1/b1 neurons of above 10 synapses in FAFB, and 8/9 for LHAV1a1 (Cachero et al, 2020).…”

Section: Between-animal Stereotypy In Olfactory System Neuronsmentioning

confidence: 99%

Information flow, cell types and stereotypy in a full olfactory connectome

Schlegel

Bates

Stürner

et al. 2021

eLife

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132

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The hemibrain connectome provides large scale connectivity and morphology information for the majority of the central brain of Drosophila melanogaster. Using this data set, we provide a complete description of the Drosophila olfactory system, covering all first, second and lateral horn-associated third-order neurons. We develop a generally applicable strategy to extract information flow and layered organisation from connectome graphs, mapping olfactory input to descending interneurons. This identifies a range of motifs including highly lateralised circuits in the antennal lobe and patterns of convergence downstream of the mushroom body and lateral horn. Leveraging a second data set we provide a first quantitative assessment of inter- versus intra-individual stereotypy. Comparing neurons across two brains (three hemispheres) reveals striking similarity in neuronal morphology across brains. Connectivity correlates with morphology and neurons of the same morphological type show similar connection variability within the same brain as across two brains.

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Section: Between-animal Stereotypy In Olfactory System Neuronsmentioning

confidence: 99%

Information flow, cell types and stereotypy in a full olfactory connectome

Schlegel

Bates

Stürner

et al. 2021

eLife

Self Cite

132

180

View full text Add to dashboard Cite

show abstract

“…Circuit-tracing systems such as trans- Tango, TRACT, and BAcTrace are built on this principle but require the reconstitution of an exogenous, contact- or ligand-based, cell-to-cell signaling apparatus (Huang et al, 2017; Talay et al, 2017; Cachero et al, 2020). This introduces additional genetic complexity and the danger of overexpression artefacts if the foreign molecules escape synaptic confinement.…”

Section: Discussionmentioning

confidence: 99%

Changes in presynaptic gene expression during homeostatic compensation at a central synapse

Harrell

Pimentel

Miesenboeck

2020

Preprint

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Homeostatic matching of pre- and postsynaptic function has been observed in many species and neural structures, but whether transcriptional changes contribute to this form of trans-synaptic coordination remains unknown. To identify genes whose expression is altered in presynaptic neurons as a result of perturbing postsynaptic excitability, we applied a transcriptomics-friendly, temperature-inducible Kir2.1-based activity clamp at the first synaptic relay of the Drosophila olfactory system, a central synapse known to exhibit trans-synaptic homeostatic matching. Twelve hours after adult-onset suppression of activity in postsynaptic antennal lobe projection neurons, we detected changes in the expression of many genes in the third antennal segment, which houses the somata of presynaptic olfactory receptor neurons. These changes affected genes with roles in synaptic vesicle release and synaptic remodeling, including several genes implicated in homeostatic plasticity at the neuromuscular junction. At 48 hours and beyond, the transcriptional landscape was tilted toward proteostasis, energy metabolism, and cellular stress defenses, indicating that the system had been pushed to its homeostatic limits. Our data provide insights into the nature of homeostatic compensation at a central synapse and identify many genes engaged in synaptic homeostasis. The presynaptic transcriptional response to genetically targeted postsynaptic perturbations could be exploited for the construction of novel connectivity tracing tools.Significance StatementHomeostatic feedback mechanisms adjust intrinsic and synaptic properties of neurons to keep their average activity levels constant. We show that, at a central synapse in the fruit fly brain, these mechanisms include changes in presynaptic gene expression that are instructed by an abrupt loss of postsynaptic excitability. The trans-synaptically regulated genes have roles in synaptic vesicle release and synapse remodeling; protein synthesis, folding, and degradation; and energy metabolism. Our analysis suggests that similar homeostatic machinery operates at peripheral and central synapses, identifies some of its components, and potentially opens new opportunities for the development of connectivity-based gene expression systems.

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“…Circuit-tracing systems such as trans-Tango, TRACT, and BAcTrace are built on this principle but require the reconstitution of an exogenous cell-to-cell signaling apparatus (Huang et al, 2017;Talay et al, 2017;Cachero et al, 2020). The chief obstacle to the development of this retrograde tracing technology is the small, at most two-fold, changes in homeostatic gene expression we detect (Tables 5,11,and 12).…”

Section: Labeling Connections With Trans-synaptically Regulated Genes?mentioning

confidence: 99%