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Monday July 7, 2025 16:20 - 18:20 CEST
P206 Synaptic Topography Influences Dendritic Integration in Drosophila Looming Responsive Descending Neurons

Anthony Moreno-Sanchez*1, Alexander N. Vasserman1,HyoJongJang2, Bryce W. Hina2, Catherine R. von Reyn1 2, Jessica Ausborn1

1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United States.
2School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, United States.

*Email: am4946@drexel.edu
Introduction

Synapse organization plays a crucial role in neural computation, affecting dendritic integration and neuronal output [1, 2].InDrosophila melanogaster, visual projection neurons (VPNs) encode distinct visual features and relay retinotopic information from thelobulaandlobulaplate to descending neurons (DNs) in the central brain[3].DNsintegratespatially organizedvisualinformationfrom VPNsto elicitappropriatemotorresponses[4,5,6].However, the retinotopic organization of VPN-DN connections and its impact on dendritic integration remain unclear.Using electron microscopy (EM)data, computational modeling, and electrophysiology, we investigated how synaptic topography affects dendritic processing in looming-sensitive DNs.

Methods
We analyzed EM reconstructions ofDrosophilaVPN-DN circuits from theFull Adult Fly Brain(FAFB)dataset[7], using flywire.ai[8].Wedeveloped multicompartment models of 5 DNs with precise VPN synaptic locationsusingthe FAFB dataset.Using EM VPNmorphologies,we estimated the receptive fields of 6 VPN populations [4,9] and analyzed synapse organization on DN dendrites.We experimentally determined the spike initiation zone (SIZ), in our DNs of interest by tagging the endogenous voltage gated sodium channelpara.Passive properties of DNsweredeterminedusing whole-cell patch clamp electrophysiology data, by fittinghyperpolarizingexperimentalcurrent injections.Simulations were performed in the NEURONsimulationenvironment.
Results
VPN synapses formed spatially constrained clusters on DN dendritesbut lacked retinotopic organizationwithin the clusters.We found that DN morphologyand passive propertiesfilterexcitatory postsynaptic potentials (EPSPs)to achieve synaptic democracy,normalizingeach EPSPs impactattheSIZ.SimulationssuggestthatVPN synapsesfollow anear random distribution of synapsesavoiding tight clusters of synapses from individual neurons to avoid shunting.This synaptic topography,together with synaptic democracy,maintainsa linear relationship between synapse number and depolarization at the SIZ, both when activating individual VPNsand a small group of VPNs.
Discussion
DNs integrate retinotopic feature information from multiple VPN types, each targeting distinct dendritic regions.This organization strategy may enable DNs toselectively process visual features across the fly’s visual field for behavior-relevant computations.Our resultssuggestthat DN dendritic architecture and synaptic topography supports a quasi-linear integration model, in which synaptic democracy ensures consistent encoding of stimulus location via synapse numbers. These findings offer insights into synaptic organization principles andtheirrole in neural circuit function, highlighting the absence of retinotopic organization to prevent membrane shunting.



Acknowledgements
We thank Arthur Zhao forhelpwith the receptive field mapping, James M. Jeanne for help with the creation of dendrograms, and Thomas A. Ravenscroft for providing us with para-GFSTF tools for SIZ labeling.This study was supported in part by the National Institutes of Health (NINDS R01NS118562 to J.A. andC.R.v.R.), and the National Science Foundation (grant no. IOS-1921065 toC.R.v.R.).
References
1.doi:10.1038/s41583-020-0301-7
2.doi:10.1126/science.1189664
3.doi: 10.7554/eLife.21022
4.doi: 10.1038/s41586-023-05930-y
5.doi: 10.1038/nn.3741
6.doi: 10.1016/j.cub.2008.07.094
7.doi: 10.1016/j.cell.2018.06.019.
8.doi:10.1038/s41592-021-01330-0
9.doi: 10.7554/eLife.57685

Monday July 7, 2025 16:20 - 18:20 CEST
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