Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome
Open accessPublished version of a preprint
Abstract
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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The sign of a glutamatergic connection may depend on the sub-localization and ratio of receptors at recipient sites.
“The sign of a glutamatergic connection may depend on the sub-localization and ratio of receptors at recipient sites.119”
From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [119]
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- 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., & Zipursky, S. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, Los Angeles (US)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Zipursky, S. Lawrence
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2024-03
- Volume
- 112
- Issue
- 6
- Pages
- 942-958.e13
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC10957333
- OpenAlex
- W4391112813
- Cited by
- 36
- References
- 16
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 9
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- 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
- University of California, Los Angeles
- National Institutes of Health (1RF1MH117823-01, GM089778)
- 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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