Journal article
Molecular gradients shape synaptic specificity of a visuomotor transformation
Nature (London)
04 Jun 2025
PMID: 40468081
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
How does the brain convert visual input into specific motor actions1,2? In Drosophila, visual projection neurons (VPNs)3,4 perform this visuomotor transformation by converting retinal positional information into synapse number in the brain5. The molecular basis of this phenomenon remains unknown. We addressed this issue in LPLC2 (ref. 6), a VPN type that detects looming motion and preferentially drives escape behaviour to stimuli approaching from the dorsal visual field with progressively weaker responses ventrally. This correlates with a dorsoventral gradient of synaptic inputs into and outputs from LPLC2. Here we report that LPLC2 neurons sampling different regions of visual space exhibit graded expression of cell recognition molecules matching these synaptic gradients. Dpr13 shapes LPLC2 outputs by binding DIP-ε in premotor descending neurons mediating escape. Beat-VI shapes LPLC2 inputs by binding Side-II in upstream motion-detecting neurons. Gain-of-function and loss-of-function experiments show that these molecular gradients act instructively to determine synapse number. These patterns, in turn, fine-tune the perception of the stimulus and drive the behavioural response. Similar transcriptomic variation within neuronal types is observed in the vertebrate brain7 and may shape synapse number via gradients of cell recognition molecules acting through both genetically hard-wired programs and experience.
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Details
- Title
- Molecular gradients shape synaptic specificity of a visuomotor transformation
- Creators
- Mark Dombrovski - University of California, Los AngelesYixin Zang - Howard Hughes Medical InstituteGiovanni Frighetto - University of California, Los AngelesAndrea Vaccari - Middlebury College (United States, MiddleburyHyoJong Jang - Drexel UniversityParmis S Mirshahidi - University of California, Los AngelesFangming Xie - University of California, Los AngelesPiero Sanfilippo - University of California, Los AngelesBryce W Hina - Drexel UniversityAadil Rehan - University of California, Los AngelesRoni H Hussein - University of California, Los AngelesPegah S Mirshahidi - University of California, Los AngelesCatherine Lee - University of California, Los AngelesAileen Morris - University of California, Los AngelesMark A Frye - University of California, Los AngelesCatherine R von Reyn - Drexel UniversityYerbol Z Kurmangaliyev - Brandeis UniversityGwyneth M Card - Howard Hughes Medical InstituteS Lawrence Zipursky - University of California, Los Angeles
- Publication Details
- Nature (London)
- Publisher
- NATURE PORTFOLIO; BERLIN
- Number of pages
- 38
- Grant note
- HHMI-HHWF Fellowship: NEI K99EY036123, NEI K99EY036889, R01EY026031 NINDS: R01NS118562
We thank the Bloomington Stock Center (US National Institutes of Health P40OD018537), Vienna Drosophila Research Center and Janelia Fly Facility for providing fly stocks; the UCLA Technology Center for Genomics and Bioinformatics for help with library preparation and scRNA-seq; the UCLA BSCRC FACS core for assistance with FACS purification; members of the FlyWire Consortium for connectome annotation in the FAFB dataset; all members of the Zipursky laboratory for advice and comments on the manuscript; and M. Scandola and S. Min Ha for advice on calcium imaging data analysis. This work was funded by the HHMI-HHWF Fellowship (to M.D.), NEI K99EY036123 (to M.D.), NEI K99EY036889 (to G.F.), NEI R01EY026031 (to M.A.F.) and NINDS R01NS118562 (to C.R.v.R). G.M.C. is an investigator of the Howard Hughes Medical Institute. The illustration in Fig. 1a was created using BioRender (https://biorender.com).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001502122300001
- Scopus ID
- 2-s2.0-105007245251
- Other Identifier
- 991022055138804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences