{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:08:53Z","timestamp":1780463333675,"version":"3.54.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP0988227"],"award-info":[{"award-number":["DP0988227"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001061","name":"Rebecca L. Cooper Medical Research Foundation","doi-asserted-by":"publisher","award":["10163"],"award-info":[{"award-number":["10163"]}],"id":[{"id":"10.13039\/501100001061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Understanding the mechanisms underlying direction selectivity in retinal ganglion cells (RGCs) is crucial in visual neuroscience. Retinal direction selectivity is critical for gaze stabilization through optokinetic and vestibulo-ocular reflexes, and its loss impairs the ability to stabilize gaze and track moving objects, potentially impacting behaviors that rely on accurate motion detection. The prevailing hypothesis proposes that the interplay between excitatory and inhibitory inputs is pivotal for the emergence of direction selectivity in RGCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To dissect the contributions of these inputs, we employed dynamic-clamp recordings utilizing computationally modeled, synthetic excitatory and inhibitory conductances of varying amplitudes and time onsets in mouse RGCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The use of combinations of excitatory and inhibitory conductances with altered amplitude or timing in configurations not found in natural physiological conditions, allowed us to evaluate the specific contribution and impact of these modified components on direction selectivity. We found that asymmetries in both excitatory and inhibitory inputs are critical for the emergence of sharp directional tuning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings contribute to advance our understanding of the cellular and synaptic mechanisms that underlie retinal direction selectivity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1816252","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:53:21Z","timestamp":1780462401000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the role of asymmetric excitatory and inhibitory synaptic inputs to retinal ganglion cell direction selectivity"],"prefix":"10.3389","volume":"20","author":[{"given":"Jin Y.","family":"Huang","sequence":"first","affiliation":[{"name":"Education Innovation Theme, School of Medical Sciences, The University of Sydney","place":["Camperdown, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Rowland","family":"Taylor","sequence":"additional","affiliation":[{"name":"School of Optometry and Helen Wills Neuroscience Institute, University of California, Berkeley","place":["Berkeley, CA, United States"]},{"name":"Herbert Wertheim School of Optometry and Vision Science, The University of California, Berkeley","place":["Berkeley, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario A.","family":"Protti","sequence":"additional","affiliation":[{"name":"Neuroscience Theme, School of Medical Sciences, The University of Sydney","place":["Camperdown, NSW, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1126\/science.139.3553.412","article-title":"Selective sensitivity to direction of movement in ganglion cells of the rabbit retina.","volume":"139","author":"Barlow","year":"1963","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1113\/jphysiol.1965.sp007638","article-title":"The mechanism of directionally selective units in rabbit\u2019s retina.","volume":"178","author":"Barlow","year":"1965","journal-title":"J. Physiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/nature09818","article-title":"Wiring specificity in the direction-selectivity circuit of the retina.","volume":"471","author":"Briggman","year":"2011","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/nature09570","article-title":"Noise correlations improve response fidelity and stimulus encoding.","volume":"468","author":"Cafaro","year":"2010","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/j.neuron.2012.08.033","article-title":"Transient sodium current at subthreshold voltages: Activation by EPSP waveforms.","volume":"75","author":"Carter","year":"2012","journal-title":"Neuron"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1152\/jn.00283.2014","article-title":"Receptive field properties of bipolar cell axon terminals in direction-selective sublaminas of the mouse retina.","volume":"112","author":"Chen","year":"2014","journal-title":"J. Neurophysiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.neuroscience.2006.02.079","article-title":"Morphological properties of mouse retinal ganglion cells.","volume":"140","author":"Coombs","year":"2006","journal-title":"Neuroscience"},{"key":"B8","doi-asserted-by":"publisher","first-page":"9756","DOI":"10.1523\/JNEUROSCI.19-22-09756.1999","article-title":"Functional circuitry of the retinal ganglion cell\u2019s nonlinear receptive field.","volume":"19","author":"Demb","year":"1999","journal-title":"J. Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"13691","DOI":"10.1523\/JNEUROSCI.3854-09.2009","article-title":"Permanent functional reorganization of retinal circuits induced by early long-term visual deprivation.","volume":"29","author":"Di Marco","year":"2009","journal-title":"J. Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.neuroscience.2003.08.027","article-title":"Synaptic background noise controls the input\/output characteristics of single cells in an in vitro model of in vivo activity.","volume":"122","author":"Fellous","year":"2003","journal-title":"Neuroscience"},{"key":"B11","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nature01179","article-title":"Mechanisms and circuitry underlying directional selectivity in the retina.","volume":"420","author":"Fried","year":"2002","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.neuron.2005.02.007","article-title":"Directional selectivity is formed at multiple levels by laterally offset inhibition in the rabbit retina.","volume":"46","author":"Fried","year":"2005","journal-title":"Neuron"},{"key":"B13","doi-asserted-by":"publisher","first-page":"112030","DOI":"10.1016\/j.celrep.2023.112030","article-title":"Hierarchical retinal computations rely on hybrid chemical-electrical signaling.","volume":"42","author":"Hanson","year":"2023","journal-title":"Cell Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e42392","DOI":"10.7554\/eLife.42392","article-title":"Retinal direction selectivity in the absence of asymmetric starburst amacrine cell responses.","volume":"8","author":"Hanson","year":"2019","journal-title":"eLife"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e185","DOI":"10.1371\/journal.pbio.0050185","article-title":"A dendrite-autonomous mechanism for direction selectivity in retinal starburst amacrine cells.","volume":"5","author":"Hausselt","year":"2007","journal-title":"PLoS Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e50400","DOI":"10.3791\/50400","article-title":"Implementing dynamic clamp with synaptic and artificial conductances in mouse retinal ganglion cells.","volume":"75","author":"Huang","year":"2013","journal-title":"J. Vis. Exp."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4449","DOI":"10.1523\/JNEUROSCI.1391-21.2022","article-title":"Visual stimulation induces distinct forms of sensitization of on-off direction-selective ganglion cell responses in the dorsal and ventral retina.","volume":"42","author":"Huang","year":"2022","journal-title":"J. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e52949","DOI":"10.7554\/eLife.52949","article-title":"The functional organization of excitation and inhibition in the dendrites of mouse direction-selective ganglion cells.","volume":"9","author":"Jain","year":"2020","journal-title":"eLife"},{"key":"B19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1002\/cne.20631","article-title":"Diversity of ganglion cells in the mouse retina: Unsupervised morphological classification and its limits.","volume":"489","author":"Kong","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.neuron.2017.07.020","article-title":"Cross-compartmental modulation of dendritic signals for retinal direction selectivity.","volume":"95","author":"Koren","year":"2017","journal-title":"Neuron"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1016\/j.neuron.2010.11.031","article-title":"Role of ACh-GABA cotransmission in detecting image motion and motion direction.","volume":"68","author":"Lee","year":"2010","journal-title":"Neuron"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2928","DOI":"10.1016\/j.neuron.2021.07.008","article-title":"Direction selectivity in retinal bipolar cell axon terminals.","volume":"109","author":"Matsumoto","year":"2021","journal-title":"Neuron"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3277","DOI":"10.1016\/j.cub.2019.08.048","article-title":"Spatiotemporally asymmetric excitation supports mammalian retinal motion sensitivity.","volume":"29","author":"Matsumoto","year":"2019","journal-title":"Curr. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neures.2023.06.003","article-title":"Emerging computational motifs: Lessons from the retina.","volume":"196","author":"Matsumoto","year":"2023","journal-title":"Neurosci. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.neuron.2006.09.014","article-title":"Network variability limits stimulus-evoked spike timing precision in retinal ganglion cells.","volume":"52","author":"Murphy","year":"2006","journal-title":"Neuron"},{"key":"B26","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.neuron.2005.06.036","article-title":"Direction-selective dendritic action potentials in rabbit retina.","volume":"47","author":"Oesch","year":"2005","journal-title":"Neuron"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3976","DOI":"10.1523\/JNEUROSCI.5017-13.2014","article-title":"Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning.","volume":"34","author":"Park","year":"2014","journal-title":"J. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"13219","DOI":"10.1523\/JNEUROSCI.0933-15.2015","article-title":"Conditional knock-out of vesicular GABA transporter gene from starburst amacrine cells reveals the contributions of multiple synaptic mechanisms underlying direction selectivity in the retina.","volume":"35","author":"Pei","year":"2015","journal-title":"J. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1002\/cne.24207","article-title":"Directional excitatory input to direction-selective ganglion cells in the rabbit retina.","volume":"527","author":"Percival","year":"2019","journal-title":"J. Comp. Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e19463","DOI":"10.1371\/journal.pone.0019463","article-title":"Imperfect space clamp permits electrotonic interactions between inhibitory and excitatory synaptic conductances, distorting voltage clamp recordings.","volume":"6","author":"Poleg-Polsky","year":"2011","journal-title":"PLoS One"},{"key":"B31","doi-asserted-by":"publisher","first-page":"5861","DOI":"10.1523\/JNEUROSCI.4013-15.2016","article-title":"Retinal circuitry balances contrast tuning of excitation and inhibition to enable reliable computation of direction selectivity","volume":"36","author":"Poleg-Polsky","year":"2016","journal-title":"J. Neurosci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1113\/jphysiol.2013.257352","article-title":"Inner retinal inhibition shapes the receptive field of retinal ganglion cells in primate.","volume":"592","author":"Protti","year":"2014","journal-title":"J. Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e1000899","DOI":"10.1371\/journal.pcbi.1000899","article-title":"Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.","volume":"6","author":"Schachter","year":"2010","journal-title":"PLoS Comput. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1038\/s41467-021-21680-9","article-title":"Rapid multi-directed cholinergic transmission in the central nervous system.","volume":"12","author":"Sethuramanujam","year":"2021","journal-title":"Nat. Commun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.neuron.2016.04.041","article-title":"Central role for mixed acetylcholine\/GABA transmission in direction coding in the retina.","volume":"90","author":"Sethuramanujam","year":"2016","journal-title":"Neuron"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/j.neuron.2017.09.058","article-title":"\u201cSilent\u201d NMDA synapses enhance motion sensitivity in a mature retinal circuit.","volume":"96","author":"Sethuramanujam","year":"2017","journal-title":"Neuron"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1038\/nn.3565","article-title":"Direction selectivity is computed by active dendritic integration in retinal ganglion cells.","volume":"16","author":"Sivyer","year":"2013","journal-title":"Nat. Neurosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1016\/j.cub.2022.03.054","article-title":"Distinct inhibitory pathways control velocity and directional tuning in the mouse retina.","volume":"32","author":"Summers","year":"2022","journal-title":"Curr. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/cne.10323","article-title":"Large-scale morphological survey of mouse retinal ganglion cells.","volume":"451","author":"Sun","year":"2002","journal-title":"J. Comp. Neurol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"7712","DOI":"10.1523\/JNEUROSCI.22-17-07712.2002","article-title":"Diverse synaptic mechanisms generate direction selectivity in the rabbit retina.","volume":"22","author":"Taylor","year":"2002","journal-title":"J. Neurosci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nrn3165","article-title":"Direction selectivity in the retina: Symmetry and asymmetry in structure and function.","volume":"13","author":"Vaney","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1146\/annurev-vision-091517-034048","article-title":"Neural mechanisms of motion processing in the mammalian retina.","volume":"4","author":"Wei","year":"2018","journal-title":"Annu. Rev. Vis. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1113\/jphysiol.2004.076695","article-title":"Identification of ON-OFF direction-selective ganglion cells in the mouse retina.","volume":"562","author":"Weng","year":"2005","journal-title":"J. Physiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2110","DOI":"10.1016\/j.neuron.2022.04.012","article-title":"Differences in spike generation instead of synaptic inputs determine the feature selectivity of two retinal cell types.","volume":"110","author":"Wienbar","year":"2022","journal-title":"Neuron"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.neuron.2013.08.005","article-title":"The first stage of cardinal direction selectivity is localized to the dendrites of retinal ganglion cells.","volume":"79","author":"Yonehara","year":"2013","journal-title":"Neuron"},{"key":"B46","doi-asserted-by":"publisher","first-page":"4371","DOI":"10.1113\/jphysiol.2008.159020","article-title":"Synaptic physiology of direction selectivity in the retina.","volume":"586","author":"Zhou","year":"2008","journal-title":"J. Physiol."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1816252\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:53:27Z","timestamp":1780462407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1816252\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":46,"alternative-id":["10.3389\/fnins.2026.1816252"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2026.1816252","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"article-number":"1816252"}}