Origin of wiring specificity in an olfactory map revealed by neuron type–specific, time-lapse imaging of dendrite targeting

  1. Kenneth Kin Lam Wong
  2. Tongchao Li
  3. Tian-Ming Fu
  4. Gaoxiang Liu
  5. Cheng Lyu
  6. Sayeh Kohani
  7. Qijing Xie
  8. David J Luginbuhl
  9. Srigokul Upadhyayula
  10. Eric Betzig
  11. Liqun Luo

  • Curated by eLife

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    When a neuron is born it correlates with where it targets in the neuropil and this has been best demonstrated in the olfactory lobe of Drosophila. This important study uses sophisticated genetics and advanced live imaging to provide a compelling description of how neuronal dendrites explore the targeting field, eliminate excessive branches, and assort into the correct region during development. In the process, it develops valuable tools. It brings us closer to a comprehensive understanding of how the birth order of a neuron translates to dendrite patterning within the Drosophila antennal lobe circuit

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Abstract

How does wiring specificity of neural maps emerge during development? Formation of the adult Drosophila olfactory glomerular map begins with the patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type–specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon– and adaptive optical lattice light-sheet microscope–based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.

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  1. Version published to 10.7554/elife.85521 on eLife
  2. eLife

    eLife assessment

    When a neuron is born it correlates with where it targets in the neuropil and this has been best demonstrated in the olfactory lobe of Drosophila. This important study uses sophisticated genetics and advanced live imaging to provide a compelling description of how neuronal dendrites explore the targeting field, eliminate excessive branches, and assort into the correct region during development. In the process, it develops valuable tools. It brings us closer to a comprehensive understanding of how the birth order of a neuron translates to dendrite patterning within the Drosophila antennal lobe circuit

  3. eLife

    Reviewer #1 (Public Review):

    Temporal patterning allows a neural stem cell to generate different neural identities through the course of development. While this relationship has been demonstrated in many instances of stem cells and/or neurons, it is unclear how birth order translates to target specification. In this manuscript, the authors use live imaging and new tools generated from single-cell RNA sequencing data to address this issue.

    They find that neurons born from a given time window (at the resolution of early>middle>late) innervate together - and distinctly from - those born at different temporal windows, though the specifics of the innervations differ between neural stem cell lineages. They also find that neurons achieve this by extending their dendrites in exploratory directions and selectively stabilising the ones in the appropriate direction. This process likely occurs at the sub-second timescales. Finally, they also demonstrate that embryonic-born (larval-specific) neurons that remodel to integrate into adulty-specific circuitry simultaneously perform pruning and dendrite extension to integrate into the circuitry at the appropriate time.

    This is a valuable description of how developmental programmes imparted to neurons at the time of their birth might translate to their targetting and connectivity. It lays down a framework for understanding the defects in these processes.

  4. eLife

    Reviewer #2 (Public Review):

    Wong et al. studied how dendrites find specific targets during the wiring process. They used the well-established Drosophila olfactory system to address the question. Specifically, they asked how dendrites of monoglomerulous projection neuron (PN) ensemble form a stereotyped topographic map in antennal lobes. They traced the developmental history of each individual projection neuron from anterodorsal (ad) or lateral (l) lineages and found that birth origin and birth order together specify the initial exploration territory and the terminal target. They then took a step further to ask how about the embryonic-born PNs most of which undergo remodeling during metamorphosis: do they maintain their dendritic target through metamorphosis or do they integrate re-extended dendrites into the adult-specific antennal lobes? They showed that ecdysone signaling simultaneously triggers pruning of the dendrites that formed larval antennal lobes and induces the outgrowth of new dendrites to be integrated into the adult antennal lobes. The methodologies, especially ex vivo explant live imaging, established a powerful paradigm to investigate the dynamics of synapse formation during development.

  5. eLife

    **Reviewer #3 (Public Review):
    **
    In this study, Wong et al, generate tools to genetically follow many of the Drosophila olfactory projection neurons. The antennal lobe, where 50 projection neurons need to form a stereotypic map where information from 50 types of olfactory receptor neurons is relayed to higher brain regions, is an exquisite system to study principles of neural circuit wiring. As such, the Luo lab has led the field in uncovering the mechanisms also generating tools that are needed to describe the system in unparalleled temporal and cell-type resolution. Here, they use cutting-edge genetic tools and imaging techniques to provide us with a better-than-ever understanding of the early phases of dendrite targeting and patterning of projection neurons.

    Using these refined genetic tools, often allowing them to visualize two types of projection neurons at a time, they uncovered several important principles of dendrite targeting. They found that dendrite targeting is divided into two major steps - first, projection neurons target their dendrites to a few distinct locations, thereby forming a proto-map. This initial targeting is dictated by the combination of their birth time and lineage. As a second step, neurons pattern their dendrites into the adult-specific location by a dynamic process in which net growth is dictated by a balance between stabilization and retraction of dendritic processes. Finally, they found that the embryonic-born projection-neurons, which undergo developmental remodeling that include pruning of their connections to the larval antennal lobe (as it undergoes degeneration) and regrowth into the adult antennal lobe. Surprisingly, and in contrast to other remodeling neurons in Drosophila, pruning and regrowth occur simultaneously.

    While the strong part of the paper is the cutting-edge tools, coupled with exceptional imaging strategies, its main weakness stems from the decision to remain in the descriptive realm.

  6. Version published to 10.1101/2022.12.28.522173v1 on bioRxiv