biostudies-literatureGrimes WNNational Institute of Neurological Disorders and StrokeIntramural NIH HHSNEI NIH HHSNational Eye InstituteResearch to Prevent Blindness315-328.e4https://www.ebi.ac.uk/biostudies/studies/S-EPMC8792273biostudies-literatureUnknown32(2)The morphology of retinal neurons strongly influences their physiological function. Ganglion cell (GC) dendrites ramify in distinct strata of the inner plexiform layer (IPL) so that GCs responding to light increments (ON) or decrements (OFF) receive appropriate excitatory inputs. This vertical stratification prescribes response polarity and ensures consistent connectivity between cell types, whereas the lateral extent of GC dendritic arbors typically dictates receptive field (RF) size. Here, we identify circuitry in mouse retina that contradicts these conventions. AII amacrine cells are interneurons understood to mediate "crossover" inhibition by relaying excitatory input from the ON layer to inhibitory outputs in the OFF layer. Ultrastructural and physiological analyses show, however, that some AIIs deliver powerful inhibition to OFF GC somas and proximal dendrites in the ON layer, rendering the inhibitory RFs of these GCs smaller than their dendritic arbors. This OFF pathway, avoiding entirely the OFF region of the IPL, challenges several tenets of retinal circuitry. These results also indicate that subcellular synaptic organization can vary within a single population of neurons according to their proximity to potential postsynaptic targets.Current biology : CBDendro-somatic synaptic inputs to ganglion cells contradict receptive field and connectivity conventions in the mammalian retina.PMC8792273EY028111R01 EY017836Z01 NS003039R01 EY028111EY017836NS003039Sedlacek MRieke FTian HMusgrove MDiamond JSGrimes WNSinger JHHoon MNath AfalseDendro-somatic synaptic inputs to ganglion cells contradict receptive field and connectivity conventions in the mammalian retina.The morphology of retinal neurons strongly influences their physiological function. Ganglion cell (GC) dendrites ramify in distinct strata of the inner plexiform layer (IPL) so that GCs responding to light increments (ON) or decrements (OFF) receive appropriate excitatory inputs. This vertical stratification prescribes response polarity and ensures consistent connectivity between cell types, whereas the lateral extent of GC dendritic arbors typically dictates receptive field (RF) size. Here, we identify circuitry in mouse retina that contradicts these conventions. AII amacrine cells are interneurons understood to mediate "crossover" inhibition by relaying excitatory input from the ON layer to inhibitory outputs in the OFF layer. Ultrastructural and physiological analyses show, however, that some AIIs deliver powerful inhibition to OFF GC somas and proximal dendrites in the ON layer, rendering the inhibitory RFs of these GCs smaller than their dendritic arbors. This OFF pathway, avoiding entirely the OFF region of the IPL, challenges several tenets of retinal circuitry. These results also indicate that subcellular synaptic organization can vary within a single population of neurons according to their proximity to potential postsynaptic targets.2022-01-01T00:00:00Z2022 Jan2025-04-19T14:05:42.56Z2025-04-19T14:05:42.56ZS-EPMC87922733482276710.1016/j.cub.2021.11.005