Exploring Descending Neurons within the Brain

Author

Matthew Q. Clark

Goal

The goal of this lab is to understand how neural lineages help to build functional circuitry. Though the function of some of these neurons isn’t completely understood, having a connectivity map can help us generate hypotheses about circuit function and also learn about the developmental origins of these circuits.

CATMAID (Instructions for Tracing Neurons)

With a stable internet connection open CATMAID to access the L1 brain.

Schneider-Mizell et al. (2016) is an early paper that described the utility of platform

For how-to movies see here

(a) Add Neurons from your Lineage to the Selection Table
(b) Display Network of Connectivity
(c) Display your neuron
(d) Export a Movie
(e) Rotate View Turn on z Plane
(f) Show a Connectivity Graph
(g) Show Pre Post Sites
(h) Show Table of Synaptic Partners
Figure 1: How-to videos for CATMAID

To do a screenshot in windows check here

For a copy of today’s talk click here

For this module you can work in pairs!

Part I: Exploring the connections between neurons in a known circuit

We will be working with neurons:

  1. MDNa_left; pair 1 left
  2. MDNa_right; pair 2 right
  3. MDNb_right; pair 1 right
  4. MDNb_left; pair 2 left

Display your neuron:

  1. Click on the widget that looks like a neuron and then press the / on your keyboard
  2. Type in the “annotated” neuron box “DNs from Brain Akira” and change to show 100 entries instead of 50
  3. Select the boxes that say MDNa_left; pair 1 left, MDNa_right; pair 2 right, MDNb_right; pair 1 right, and MDNb_left; pair 2 left
  4. Open the 3D viewer and click append (make sure the box next to append says Neuron Search 1)
  5. Within the 3D viewer press view settings
    1. Find the drop down that says volume and then click the box next to CNS
    2. Press the check mark next to floor to get rid of the grid on the 3D view screen
  6. Now press View within the 3D viewer and then press the box that says ZX to get it in the correct orientation

Show a presynaptic site (red points): receiving information

  1. In the 3D viewer go to view setting
  2. In the box next to Node handle scaling - increase the number until the red dots on the neurons are clearly visible

Where are the red points mainly located? The VNC or the cerebral hemispheres?

Show a postsynaptic site (cyan points): putting out information

  1. In the box next to link site scaling, increase the number until the blue dots on the neuron are clearly visible.

Where are the blue points located on the neuron? Are there more on the VNC or in the cerebral hemispheres?

Show table of synaptic partners:

Click on this widget:

Display network of connectivity:

Click on this widget:

Connectivity of Carreira-Rosario et al. (2018)

  1. Go back to the neuron search window and in the annotated section copy and past Carreira-Rosario et al. (2018) and press submit
  2. Open the 3D viewer and click append (make sure the box next to append says Neuron Search 1)
  3. Show table of synaptic partners:
    1. Click on the widget

Part II: Exploring the connections between neurons in an unknown circuit

Useful widgets:

  • shows keyboard shortcuts
  • neuron search (‘/’ also opens this widget)
  • 3D viewer of selected skeletons (use this in conjunction with the widget to manage list of skeletons)

Fun search terms:

  • “Whole motor neurons at A1 segment akira”
  • “DNs from Brain akira”
  • “DNs from SEZ akira”
  • et al

Papers to explore neural circuits:

  • Zwart et al. (2016)
  • Masson et al. (2020)
  • Burgos et al. (2018)
  • Eschbach et al. (2020)
  • Carreira-Rosario et al. (2018)
  • Miroschnikow et al. (2018)
  • Zarin, Mark, Cardona, Litwin-Kumar, & Doe (2019)
  • Mark et al. (2021)
  • Berck et al. (2016)
  • Eichler et al. (2017)
  • Andrade et al. (2019)
  • Larderet et al. (2017)
  • Ohyama et al. (2015)
  • Jovanic et al. (2016)
  • Schlegel et al. (2016)
  • Jovanic et al. (2019)
  • Fushiki et al. (2016)
  • Takagi et al. (2017)
  • Tastekin et al. (2018)
  • Imambocus et al. (2022)
  • Kohsaka et al. (2019)
  • Heckscher et al. (2015)
  • Gerhard, Andrade, Fetter, Cardona, & Schneider-Mizell (2017)

References

Andrade, I. V., Riebli, N., Nguyen, B.-C. M., Omoto, J. J., Cardona, A., & Hartenstein, V. (2019). Developmentally arrested precursors of pontine neurons establish an embryonic blueprint of the drosophila central complex. Current Biology, 29(3), 412–425.e3. https://doi.org/10.1016/j.cub.2018.12.012
Berck, M. E., Khandelwal, A., Claus, L., Hernandez-Nunez, L., Si, G., Tabone, C. J., … Cardona, A. (2016). The wiring diagram of a glomerular olfactory system. eLife, 5. https://doi.org/10.7554/elife.14859
Burgos, A., Honjo, K., Ohyama, T., Qian, C. S., Shin, G. J., Gohl, D. M., … Grueber, W. B. (2018). Nociceptive interneurons control modular motor pathways to promote escape behavior in drosophila. eLife, 7. https://doi.org/10.7554/elife.26016
Carreira-Rosario, A., Zarin, A. A., Clark, M. Q., Manning, L., Fetter, R. D., Cardona, A., & Doe, C. Q. (2018). MDN brain descending neurons coordinately activate backward and inhibit forward locomotion. eLife, 7. https://doi.org/10.7554/elife.38554
Eichler, K., Li, F., Litwin-Kumar, A., Park, Y., Andrade, I., Schneider-Mizell, C. M., … Cardona, A. (2017). The complete connectome of a learning and memory centre in an insect brain. Nature, 548(7666), 175–182. https://doi.org/10.1038/nature23455
Eschbach, C., Fushiki, A., Winding, M., Schneider-Mizell, C. M., Shao, M., Arruda, R., … Zlatic, M. (2020). Recurrent architecture for adaptive regulation of learning in the insect brain. Nature Neuroscience, 23(4), 544–555. https://doi.org/10.1038/s41593-020-0607-9
Fushiki, A., Zwart, M. F., Kohsaka, H., Fetter, R. D., Cardona, A., & Nose, A. (2016). A circuit mechanism for the propagation of waves of muscle contraction in drosophila. eLife, 5. https://doi.org/10.7554/elife.13253
Gerhard, S., Andrade, I., Fetter, R. D., Cardona, A., & Schneider-Mizell, C. M. (2017). Conserved neural circuit structure across drosophila larval development revealed by comparative connectomics. eLife, 6. https://doi.org/10.7554/elife.29089
Heckscher, E. S., Zarin, A. A., Faumont, S., Clark, M. Q., Manning, L., Fushiki, A., … Doe, C. Q. (2015). Even-skipped+ interneurons are core components of a sensorimotor circuit that maintains left-right symmetric muscle contraction amplitude. Neuron, 88(2), 314–329. https://doi.org/10.1016/j.neuron.2015.09.009
Imambocus, B. N., Zhou, F., Formozov, A., Wittich, A., Tenedini, F. M., Hu, C., … Soba, P. (2022). A neuropeptidergic circuit gates selective escape behavior of drosophila larvae. Current Biology, 32(1), 149–163.e8. https://doi.org/10.1016/j.cub.2021.10.069
Jovanic, T., Schneider-Mizell, C. M., Shao, M., Masson, J.-B., Denisov, G., Fetter, R. D., … Zlatic, M. (2016). Competitive disinhibition mediates behavioral choice and sequences in drosophila. Cell, 167(3), 858–870.e19. https://doi.org/10.1016/j.cell.2016.09.009
Jovanic, T., Winding, M., Cardona, A., Truman, J. W., Gershow, M., & Zlatic, M. (2019). Neural substrates of drosophila larval anemotaxis. Current Biology, 29(4), 554–566.e4. https://doi.org/10.1016/j.cub.2019.01.009
Kohsaka, H., Zwart, M. F., Fushiki, A., Fetter, R. D., Truman, J. W., Cardona, A., & Nose, A. (2019). Regulation of forward and backward locomotion through intersegmental feedback circuits in drosophila larvae. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-10695-y
Larderet, I., Fritsch, P. M., Gendre, N., Neagu-Maier, G. L., Fetter, R. D., Schneider-Mizell, C. M., … Sprecher, S. G. (2017). Organization of the drosophila larval visual circuit. eLife, 6. https://doi.org/10.7554/elife.28387
Mark, B., Lai, S.-L., Zarin, A. A., Manning, L., Pollington, H. Q., Litwin-Kumar, A., … Doe, C. Q. (2021). A developmental framework linking neurogenesis and circuit formation in the drosophila CNS. eLife, 10. https://doi.org/10.7554/elife.67510
Masson, J.-B., Laurent, F., Cardona, A., Barré, C., Skatchkovsky, N., Zlatic, M., & Jovanic, T. (2020). Identifying neural substrates of competitive interactions and sequence transitions during mechanosensory responses in drosophila. PLOS Genetics, 16(2), e1008589. https://doi.org/10.1371/journal.pgen.1008589
Miroschnikow, A., Schlegel, P., Schoofs, A., Hueckesfeld, S., Li, F., Schneider-Mizell, C. M., … Pankratz, M. J. (2018). Convergence of monosynaptic and polysynaptic sensory paths onto common motor outputs in a drosophila feeding connectome. eLife, 7. https://doi.org/10.7554/elife.40247
Ohyama, T., Schneider-Mizell, C. M., Fetter, R. D., Aleman, J. V., Franconville, R., Rivera-Alba, M., … Zlatic, M. (2015). A multilevel multimodal circuit enhances action selection in drosophila. Nature, 520(7549), 633–639. https://doi.org/10.1038/nature14297
Schlegel, P., Texada, M. J., Miroschnikow, A., Schoofs, A., Hückesfeld, S., Peters, M., … Pankratz, M. J. (2016). Synaptic transmission parallels neuromodulation in a central food-intake circuit. eLife, 5. https://doi.org/10.7554/elife.16799
Schneider-Mizell, C. M., Gerhard, S., Longair, M., Kazimiers, T., Li, F., Zwart, M. F., … Cardona, A. (2016). Quantitative neuroanatomy for connectomics in drosophila. eLife, 5. https://doi.org/10.7554/elife.12059
Takagi, S., Cocanougher, B. T., Niki, S., Miyamoto, D., Kohsaka, H., Kazama, H., … Nose, A. (2017). Divergent connectivity of homologous command-like neurons mediates segment-specific touch responses in drosophila. Neuron, 96(6), 1373–1387.e6. https://doi.org/10.1016/j.neuron.2017.10.030
Tastekin, I., Khandelwal, A., Tadres, D., Fessner, N. D., Truman, J. W., Zlatic, M., … Louis, M. (2018). Sensorimotor pathway controlling stopping behavior during chemotaxis in the drosophila melanogaster larva. eLife, 7. https://doi.org/10.7554/elife.38740
Zarin, A. A., Mark, B., Cardona, A., Litwin-Kumar, A., & Doe, C. Q. (2019). A multilayer circuit architecture for the generation of distinct locomotor behaviors in drosophila. eLife, 8. https://doi.org/10.7554/elife.51781
Zwart, M. F., Pulver, S. R., Truman, J. W., Fushiki, A., Fetter, R. D., Cardona, A., & Landgraf, M. (2016). Selective inhibition mediates the sequential recruitment of motor pools. Neuron, 91(3), 615–628. https://doi.org/10.1016/j.neuron.2016.06.031