The laminar organization of the Drosophila ellipsoid body is semaphorin-dependent and prevents the formation of ectopic synaptic connections

Xie, Xiaojun; Tabuchi, Masashi; Brown, Matthew; Mitchell, Sarah; Wu, Mark N.; Kolodkin, Alex L.

doi:10.7554/elife.25328

Cited by 50 publications

(46 citation statements)

References 75 publications

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“…In Drosophila, this tethering is thought to come from a large population of inhibitory ring neurons (Hanesch et al, 1989;Homberg et al, 2018;Lin et al, 2013;Omoto et al, 2018;Xie et al, 2017;Young and Armstrong, 2010). However, this has not yet been verified experimentally.…”

Section: Ring Neurons Tether the Compass To Visual Scenes By Selectivmentioning

confidence: 99%

The neuroanatomical ultrastructure and function of a biological ring attractor

Turner-Evans

Jensen

Ali

et al. 2019

Preprint

105

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Neural representations of head direction have been discovered in many different species. A large body of theoretical work has proposed that the dynamics associated with these representations might be generated, maintained, and updated by recurrent network structures called ring attractors. Ring attractor models rely on specific assumptions about the structure of excitatory and inhibitory connectivity. These assumptions have been difficult to test directly. We therefore performed electron-microscopy-based circuit reconstruction and RNA profiling of identified cell types in the heading direction system of Drosophila melanogaster to directly examine excitatory and inhibitory synaptic connectivity, generating a dataset that should serve as a reference for future functional studies of the network. Consistent with several theoretical models, we identified network motifs that have been hypothesized to maintain the heading representation in darkness, update it when the animal turns, and tether it to visual cues. Genetically targeted two-photon calcium imaging and thermogenetic perturbation of the constituent neuron types during behavior provided additional support for these functional roles. However, we also discovered network motifs absent in current models, including a surprising degree of recurrence between arbors of different neurons with mixed pre-and post-synaptic specializations. Overall, our results confirm that the Drosophila heading direction network contains the core components of a ring attractor while also revealing unpredicted structural features that might enable the heading system to accurately track the animal's heading with a small number of neurons. Importantly, however, these and other models of attractor networks in the fly have assumed the circuit's connectivity based on relatively indirect evidence (Cope et al., 2017;Han et al., 2019;Kakaria and de Bivort, 2017;Kim et al., 2017;Su et al., 2017;Turner-Evans et al., 2017). For example, the location of pre-and post-synaptic arbors has been inferred from whether neural processes visible in light-microscopic images seem spine-or bouton-like in specific substructures (Hanesch et al., 1989;Lin et al., 2013;Wolff et al., 2015). The hypothesized connectivity of the circuit has then been derived from light-level overlap between the putatively pre-and post-synaptic arbors of neurons . In Drosophila, such conclusions have been bolstered by employing GFP-reconstitution-acrosssynaptic-partners (GRASP) (Xie et al., 2017) and trans-Tango (Omoto et al., 2018) techniques. Although both GRASP and trans-Tango are powerful techniques, their reliability and accuracy when used to estimate pairwise connectivity is limited (Lee et al., 2017; Talay et al., 2017). Similarly, measurements of functional connectivity by optogenetic stimulation of one neuron type and calcium imaging of another (Franconville et al., 2018) cannot conclusively establish the presence or absence of monosynaptic connectivity.In the current study, we established the synaptic-and cellular-resolution str...

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Section: Ring Neurons Tether the Compass To Visual Scenes By Selectivmentioning

confidence: 99%

The neuroanatomical ultrastructure and function of a biological ring attractor

Turner-Evans

Jensen

Ali

et al. 2019

Preprint

105

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“…1c-h; Supplemental Video 3 show details of these structures and single-cell identities). The stratified organization of the nerve ring neuropil, resolved here at single neurite level, is reminiscent of laminar organizations in the Drosophila nervous system 42,43 , and in the vertebrate retina and the brain cortex 44,45 .We observed that not all computationally clustered neurites followed simple bundled paths through the neuropil. In Strata 1 (S1), 32 anterior sensory neurons project perpendicular to the nerve ring bundle before making a 180º curl and returning to the anterior limits of the neuropil, where they terminate as synaptic endplates (Fig.…”

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confidence: 57%

“…Overall, our analyses reveal design principles at varying degrees of granularityfrom single 'rich-club neuron' morphologies that functionally bridge different strata, to layered bundles that segregate sensory-motor information onto topological maps. These design principles are important organizational units in neuroscience-'rich-clubs' in the context of brain networks 18,21 , laminar organization in the context of brain structures [42][43][44][45] and topological maps in the context of vertebrate sensory systems [51][52][53] . We map them in the context of the neuropil architecture and resolve them for C. elegans at cellular and synaptic scales.…”

Section: Unassigned Cells Correspond To 'Rich-club' Interneurons Thatmentioning

confidence: 99%

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Structural and developmental principles of neuropil assembly inC. elegans

Moyle

Barnes

Kuchroo

et al. 2020

Preprint

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To visualize DC cluster relationships we developed C-PHATE, an extension of PHATE 30 capable of generating a 3D representation of the multigranular structures in the DC hierarchical tree ( Fig. 1a,b; see Methods). Quantitative comparisons of DC/C-PHATE results revealed similar clustering behaviors between the two separately analyzed nervering reconstructions (Adjusted Rand Index (ARI) of 0.7; Extended Data Fig. 1a,b), consistent with the long-accepted qualitative descriptions of the stereotyped structure for the C. elegans nerve ring 3,31 , and recent analyses of neurite adjacencies 22 . Examination of the cluster patterns through the iterations of DC revealed known cell-cell interactions and behavioral circuits ( Fig. 1b,c; Extended Data Fig. 2a,b; [32][33][34][35][36][37][38][39] ), consistent with behavioral and connectomic studies 10,19,20 . The multigranular outputs of the DC/C-PHATE results enabled understanding of the cell-cell interactions within the context of functional circuits, and the functional circuits within the context of the larger bundles of the neuropil.Comparisons of the modularity score, a measure of cluster robustness 40,41 , was highest when the majority of neurites were grouped into four super-clusters ( Fig. 1b; Extended Data Fig. 1a,b; Supplemental Video 1,2; see Methods). Overlaying our analysis of these four super-clusters (see Methods) onto the anatomy of the nerve ring revealed that they correspond to four distinct and tightly grouped bundles within the greater neuropil, circling the pharynx isthmus and stacked along the anterior-posterior axis of the animal. These clusters are herein called S1, S2, S3 and S4 for Stratum 1 etc. (Fig. 1c; Extended Data Fig. 1c-h; Supplemental Video 3 show details of these structures and single-cell identities). The stratified organization of the nerve ring neuropil, resolved here at single neurite level, is reminiscent of laminar organizations in the Drosophila nervous system 42,43 , and in the vertebrate retina and the brain cortex 44,45 .We observed that not all computationally clustered neurites followed simple bundled paths through the neuropil. In Strata 1 (S1), 32 anterior sensory neurons project perpendicular to the nerve ring bundle before making a 180º curl and returning to the anterior limits of the neuropil, where they terminate as synaptic endplates (Fig. 1d; Extended Data Fig. 3a-d; 3,46 ). These uniquely shaped S1 neurons looped at the borders of the S2/S3/S4 bundles. The anterior loops encase ~90% of S2, and the posterior loops encase ~84% of S3 and 100% of S4 ( Fig. 1d-g; Extended Data Fig. 3e-k ; SupplementalVideo 5; Supplemental Table 1). We found that the 32 axons form a six-fold symmetrical honeycomb structure along the neuropil's arc, creating a scaffold that encapsulates the different strata ( Fig. 1g; Extended Data Fig. 3e-h; Supplemental Video 4).The architecture of the neuropil reflects functional segregation of distinct sensory information streams and motor outputs.C. elegans neurons can be divided into three categories ...

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“…To address which ring neurons receive stimuli from TuBusup, we used high-resolution ExM imaging and confirmed that EB-R2/R4m neurons labeled by the R32H08-LexA show potent overlap with the TuBusup (Figure 6c) (Xie et al, 2017), other layers of EB ring neurons barely connect to that part of BUsup (data not shown). The data suggest that APDNs specifically activate TuBusup and then input to EB-R2/R4m neurons, which are essential for sleep and arousal regulation.…”

Section: Lexa >Lexaop-flp Uas-frt-stop-frt-cschrimson) Immunohistocmentioning

confidence: 91%

A circadian output circuit controls sleep-wake arousal threshold in Drosophila

Guo

Holla

et al. 2018

Preprint

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The Drosophila core circadian circuit contains distinct groups of interacting neurons that give rise to diurnal sleep-wake patterns. Previous work showed that a subset of Dorsal Neurons 1 (DN1s) are sleep-promoting through their inhibition of activity-promoting circadian pacemakers. Here we show that these anterior-projecting DNs (APDNs) also "exit" the circadian circuitry and communicate with the homeostatic sleep center in higher brain regions to regulate sleep and sleep-wake arousal threshold.These APDNs connect to a small discrete subset of tubercular-bulbar neurons, which are connected in turn to specific sleep-centric Ellipsoid Body (EB)-Ring neurons of the central complex. Remarkably, activation of the APDNs produces sleep-like oscillations in the EB and also raises the arousal threshold, which requires neurotransmission throughout the circuit. The data indicate that this APDN-TuBusup-EB circuit temporally regulates sleep-wake arousal threshold in addition to the previously defined role of the TuBu-EB circuit in vision, navigation and attention.

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The laminar organization of the Drosophila ellipsoid body is semaphorin-dependent and prevents the formation of ectopic synaptic connections

Cited by 50 publications

References 75 publications

The neuroanatomical ultrastructure and function of a biological ring attractor

The neuroanatomical ultrastructure and function of a biological ring attractor

Structural and developmental principles of neuropil assembly inC. elegans

A circadian output circuit controls sleep-wake arousal threshold in Drosophila

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