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PreprintCited by 36Neuroscience and Neuropharmacology ResearchNeurobiology and Insect Physiology ResearchNicotinic Acetylcholine Receptors Study

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Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome

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Sanfilippo, Piero, Kim, Alexander J., Bhukel, Anuradha, Yoo, Juyoun, Mirshahidi, Pegah S., Pandey, Vijaya, Bevir, Harry, Yuen, Ashley, Mirshahidi, Parmis S., Guo, Peiyi, Li, Hong-Sheng, Wohlschlegel, James A., Aso, Yoshinori, Lawrence Zipursky, S.·2023·Neuron
DOI 10.1101/2023.10.02.560011PMC PMC10957333

Preprint — published as 10.1016/j.neuron.2023.12.014 · Paper page

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Abstract

Summary: Neurons express different combinations of neurotransmitter receptor (NR) subunits and receive inputs from multiple neuron types expressing different neurotransmitters. Localizing NR subunits to specific synaptic inputs has been challenging. Here we use epitope tagged endogenous NR subunits, expansion light-sheet microscopy, and EM connectomics to molecularly characterize synapses in Drosophila. We show that in directionally selective motion sensitive neurons, different multiple NRs elaborated a highly stereotyped molecular topography with NR localized to specific domains receiving cell-type specific inputs. Developmental studies suggested that NRs or complexes of them with other membrane proteins determines patterns of synaptic inputs. In support of this model, we identify a transmembrane protein associated selectively with a subset of spatially restricted synapses and demonstrate through genetic analysis its requirement for synapse formation. We propose that mechanisms which regulate the precise spatial distribution of NRs provide a molecular cartography specifying the patterns of synaptic connections onto dendrites.

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Research works printed but not linked: 80

  1. 10.1002/cpcb.56 · DOI
  2. 10.7554/eLife.49257 · DOI · Paper page
  3. 10.1016/j.neuron.2016.02.015 · DOI · Paper page
  4. 10.7554/elife.53350 · DOI · Paper page
  5. 2015, ELISA, Methods and Protocols, Methods Mol. Biol, 1318, 173
  6. 10.1074/jbc.M211719200 · DOI
  7. 2022, Apical–basal polarity and the control of epithelial form and function, Nat. Rev. Mol. Cell Biol, 23, 559, 10.1038/s41580-022-00465-y · DOI · Paper page
  8. 10.1046/j.0022-3042.2001.00685.x · DOI
  9. 10.1126/science.1257998 · DOI
  10. 10.1126/science.1260088 · DOI
  11. 10.1016/j.neuron.2013.12.021 · DOI
  12. 10.3389/fnmol.2019.00154 · DOI
  13. 2008, MaxQuant enables high peptide identification rates, individualized p, p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol, 26, 1367
  14. 2019, Chemoconnectomics: Mapping Chemical Transmission in Drosophila, Neuron, 101, 876, 10.1016/j.neuron.2019.01.045 · DOI · Paper page
  15. 10.1124/mol.107.039180 · DOI · Paper page
  16. 10.7554/eLife.62953 · DOI
  17. Feng, L. , Zhao, T. , and Kim, J . (2015). neuTube 1.0: A New Design for Efficient Neuron Reconstruction Software Based on the SWC Format 123. ENeuro 2, ENEURO.0049-14.2014. · DOI
  18. 1989, The optic lobe of Drosophila melanogaster, I. A Golgi analysis of wild-type structure. Cell Tissue Res, 258, 441
  19. 10.1073/pnas.2022580118 · DOI · Paper page
  20. 2018, Active Zone Scaffold Protein Ratios Tune Functional Diversity across Brain Synapses, Cell Rep, 23, 1259, 10.1016/j.celrep.2018.03.126 · DOI
  21. Gao, R. , Asano, S.M. , Upadhyayula, S. , Pisarev, I. , Milkie, D.E. , Liu, T.-L. , Singh, V. , Graves, A. , Huynh, G.H. , Zhao, Y. , et al. (2019). Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution. Science 363, eaau8302. · DOI
  22. 10.1038/sj.bjp.0705818 · DOI
  23. 2019, The ALFA-tag is a highly versatile tool for nanobody-based bioscience applications, Nat. Commun, 10, 4403, 10.1038/s41467-019-12301-7 · DOI
  24. 10.1007/978-1-4939-2687-9_22 · DOI
  25. 10.1038/s41586-022-04428-3 · DOI · Paper page
  26. 2018, Simple integration of fast excitation and offset, delayed inhibition computes directional selectivity in Drosophila, Nat. Neurosci, 21, 250, 10.1038/s41593-017-0046-4 · DOI · Paper page
  27. 10.1038/s41592-019-0650-1 · DOI
  28. 2014, Generation of antibodies against membrane proteins, Biochim. Biophys. Acta (BBA) - Proteins Proteom, 1844, 1920, 10.1016/j.bbapap.2014.08.007 · DOI
  29. 2021, Functional Characteristics of the Lepidopteran Ionotropic GABA Receptor 8916 Subunit Interacting with the LCCH3 or the RDL Subunit, J. Agric. Food Chem, 69, 11582, 10.1021/acs.jafc.1c00385 · DOI
  30. 10.1038/S41596-018-0082-X · DOI
  31. Jami-Alahmadi, Y. , Pandey, V. , Mayank, A.K. , and Wohlschlegel, J.A . (2021). A Robust Method for Packing High Resolution C18 RP-nano-HPLC Columns. J. Vis. Exp. · DOI
  32. 10.1016/j.celrep.2012.09.011 · DOI · Paper page
  33. 10.7554/elife.51539 · DOI
  34. 2020, Trafficking and Activity of Glutamate and GABA Receptors: Regulation by Cell Adhesion Molecules, Neurosci, 26, 415
  35. 10.1016/j.jinsphys.2013.06.005 · DOI
  36. 10.1016/j.celrep.2019.12.018 · DOI · Paper page
  37. 10.1016/J.NEURON.2020.10.006 · DOI · Paper page
  38. 10.1186/1471-2202-13-73 · DOI
  39. 2016, Presynaptic Neuronal Pentraxin Receptor Organizes Excitatory and Inhibitory Synapses, J. Neurosci, 37, 1062
  40. 10.1016/S0896-6273(00)81135-6 · DOI
  41. 10.1016/j.neuron.2007.10.036 · DOI
  42. 10.1073/pnas.1511910112 · DOI
  43. 10.1016/1047-3203(90)90014-M · DOI
  44. MICrONS Consortium, Bae, J.A. , Baptiste, M. , Bodor, A.L. , Brittain, D. , Buchanan, J. , Bumbarger, D.J. , Castro, M.A. , Celii, B. , Cobos, E. , et al. (2023). Functional connectomics spanning multiple areas of mouse visual cortex. BiorXiv 2021.07.28.454025.
  45. 10.1016/j.cell.2016.04.044 · DOI
  46. 10.1523/JNEUROSCI.2300-15.2016 · DOI
  47. 10.1523/JNEUROSCI.23-37-11554.2003 · DOI · Paper page
  48. 10.1073/pnas.1111704108 · DOI
  49. 10.1073/pnas.1506763112 · DOI · Paper page
  50. 10.1093/bioinformatics/btt276 · DOI
  51. 2021, Neuronal diversity and convergence in a visual system developmental atlas, Nature, 589, 88, 10.1038/s41586-020-2879-3 · DOI · Paper page
  52. 10.1113/jphysiol.2011.216028 · DOI
  53. 10.1534/genetics.110.119917 · DOI · Paper page
  54. 10.1080/01677060802471684 · DOI
  55. 10.1073/pnas.1318481110 · DOI
  56. 10.15252/embj.201695709 · DOI · Paper page
  57. 2017, Intra-neuronal Competition for Synaptic Partners Conserves the Amount of Dendritic Building Material, Neuron, 93, 632, 10.1016/j.neuron.2016.12.043 · DOI · Paper page
  58. 10.7554/eLife.57443 · DOI · Paper page
  59. 10.1038/nmeth.2019 · DOI · Paper page
  60. 1998, Dα3, a New Functional α Subunit of Nicotinic Acetylcholine Receptors from Drosophila, J. Neurochem, 71, 853, 10.1046/j.1471-4159.1998.71020853.x · DOI
  61. Shapson-Coe, A. , Januszewski, M. , Berger, D.R. , Pope, A. , Wu, Y. , Blakely, T. , Schalek, R.L. , Li, P.H. , Wang, S. , Maitin-Shepard, J. , et al. (2021). A connectomic study of a petascale fragment of human cerebral cortex. BioRxiv 2021.05.29.446289. · DOI · Paper page
  62. 10.7554/ELIFE.40025 · DOI · Paper page
  63. 10.1016/S0165-0270(02)00362-X · DOI
  64. 2021, The cell biology of synapse formation, J. Cell Biol, 220, e202103052, 10.1083/jcb.202103052 · DOI · Paper page
  65. 10.1038/nature12450 · DOI · Paper page
  66. 10.1073/pnas.1509820112 · DOI · Paper page
  67. 10.7554/eLife.26975 · DOI · Paper page
  68. 10.7554/eLife.24394 · DOI · Paper page
  69. 2021, Confocal Microscopy, Methods and Protocols, Methods Mol. Biol, 2304, 147
  70. 10.1038/nbt.3625 · DOI
  71. 10.1038/nmeth.3365 · DOI
  72. Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis (Springer-Verlag New York). · DOI
  73. Winding, M. , Pedigo, B.D. , Barnes, C.L. , Patsolic, H.G. , Park, Y. , Kazimiers, T. , Fushiki, A. , Andrade, I.V. , Khandelwal, A. , Valdes-Aleman, J. , et al. (2023). The connectome of an insect brain. Science 379, eadd9330. · DOI · Paper page
  74. 2018, Interactions between the Ig-Superfamily Proteins DIP-α and Dpr6/10 Regulate Assembly of Neural Circuits, Neuron, 100, 1369, 10.1016/j.neuron.2018.11.001 · DOI
  75. 10.1038/s41467-018-03947-w · DOI
  76. 10.1016/j.cell.2016.05.031 · DOI
  77. 10.1002/cne.10155 · DOI
  78. 10.1016/j.neuron.2010.04.008 · DOI
  79. ffrench-Constant, R.H., 1995, Subunit composition determines picrotoxin and bicuculline sensitivity of Drosophila gamma- aminobutyric acid receptors, Mol. Pharmacol, 48, 835
  80. 10.1016/j.cell.2018.06.019 · DOI · Paper page

Metadata

Authors
Sanfilippo, P., Kim, A. J., Bhukel, A., Yoo, J., Mirshahidi, P. S., Pandey, V., Bevir, H., Yuen, A., Mirshahidi, P. S., Guo, P., Li, H.-S., Wohlschlegel, J. A., Aso, Y., & Lawrence Zipursky, S.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of California, Los Angeles (US)
  • University of Massachusetts Chan Medical School (US)
ORCID
Venue
Neuron
Publisher
openRxiv
Published
2023-10-02
Volume
112
Issue
6
Pages
942-958.e13
ISSN
0896-6273 (ISSN-L)
DOI
10.1101/2023.10.02.560011
PMC
PMC10957333
OpenAlex
W4391112813
Cited by
36
References
1
Citations by year
2026: 14 · 2025: 13 · 2024: 9
FWCI
6.28
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Neuron (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (1rf1mh117823-01)
  • University of California, Los Angeles
  • National Institute of Mental Health (RF1 MH117823)
  • National Institute of General Medical Sciences (R01GM089778)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
neurotransmitter receptors, synaptic connectivity, connectome, Drosophila, transmembrane proteins, synaptogenesis, receptor complex

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