Dendro-somatic synaptic inputs to ganglion cells contradict receptive field and connectivity conventions in the mammalian retina

• Published in: Current biology 2022-01, Vol.32 (2), p.315-328.e4
• Main Authors: Grimes, William N., Sedlacek, Miloslav, Musgrove, Morgan, Nath, Amurta, Tian, Hua, Hoon, Mrinalini, Rieke, Fred, Singer, Joshua H., Diamond, Jeffrey S.
• Format: Article
• Language: English
• Subjects: amacrine; Amacrine Cells - physiology; Animals; calcium; channelrhodopsin; circuitry; connect; Dendrites - physiology; glycine; inhibition; Interneurons - physiology; Mammals; Mice; omic; retina; Retina - physiology; scotopic; Synapses - physiology
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2021.11.005

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. •AII amacrine cells make dendrosomatic synapses exclusively onto OFFα ganglion cells•Only AIIs located directly above OFFα ganglion cells make dendrosomatic contacts•AII dendrites express voltage-gated calcium influx near synaptic outputs•AII dendrosomatic inputs render OFFαs highly sensitive to narrow visual stimuli AII amacrine cells provide crossover inhibition to OFF-responding retinal circuits. Here, Grimes et al. show that the synaptic organization of AIIs is altered when the cells overlap in space with OFFα ganglion cell somas. AII synaptic organization is, therefore, heterogeneous and depends on proximity to specific postsynaptic partners.