Institute of Developmental Biology and Neurobiology, Johannes Gutenberg-Universität Mainz, Mainz, Germany; European Neuroscience Institute Göttingen – A Joint Initiative of the University Medical Center Göttingen and the Max-Planck-Society, Göttingen, Germany; International Max Planck Research School and Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences (GGNB) at the University of Göttingen, Göttingen, Germany
Juan Felipe Vargas-Fique
Institute of Developmental Biology and Neurobiology, Johannes Gutenberg-Universität Mainz, Mainz, Germany; European Neuroscience Institute Göttingen – A Joint Initiative of the University Medical Center Göttingen and the Max-Planck-Society, Göttingen, Germany; International Max Planck Research School and Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences (GGNB) at the University of Göttingen, Göttingen, Germany
Miriam Henning
Institute of Developmental Biology and Neurobiology, Johannes Gutenberg-Universität Mainz, Mainz, Germany; European Neuroscience Institute Göttingen – A Joint Initiative of the University Medical Center Göttingen and the Max-Planck-Society, Göttingen, Germany
Institute of Developmental Biology and Neurobiology, Johannes Gutenberg-Universität Mainz, Mainz, Germany; European Neuroscience Institute Göttingen – A Joint Initiative of the University Medical Center Göttingen and the Max-Planck-Society, Göttingen, Germany; International Max Planck Research School and Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences (GGNB) at the University of Göttingen, Göttingen, Germany
T Moritz Schladt
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Bonn, Germany
Junaid Akhtar
Institute of Developmental Biology and Neurobiology, Johannes Gutenberg-Universität Mainz, Mainz, Germany
Thomas K Berger
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Bonn, Germany; Institute of Physiology and Pathophysiology, Philipps-Universität Marburg, Marburg, Germany
Institute of Developmental Biology and Neurobiology, Johannes Gutenberg-Universität Mainz, Mainz, Germany; European Neuroscience Institute Göttingen – A Joint Initiative of the University Medical Center Göttingen and the Max-Planck-Society, Göttingen, Germany
Sensory systems sequentially extract increasingly complex features. ON and OFF pathways, for example, encode increases or decreases of a stimulus from a common input. This ON/OFF pathway split is thought to occur at individual synaptic connections through a sign-inverting synapse in one of the pathways. Here, we show that ON selectivity is a multisynaptic process in the Drosophila visual system. A pharmacogenetics approach demonstrates that both glutamatergic inhibition through GluClα and GABAergic inhibition through Rdl mediate ON responses. Although neurons postsynaptic to the glutamatergic ON pathway input L1 lose all responses in GluClα mutants, they are resistant to a cell-type-specific loss of GluClα. This shows that ON selectivity is distributed across multiple synapses, and raises the possibility that cell-type-specific manipulations might reveal similar strategies in other sensory systems. Thus, sensory coding is more distributed than predicted by simple circuit motifs, allowing for robust neural processing.