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In the retina, rod and cone pathways mediate visual signals over a billion-fold range in luminance. AII ("A-two") amacrine cells (ACs) receive signals from both pathways via different bipolar cells, enabling AIIs to operate at night and during the day. Previous work has examined luminance-dependent changes in AII gap junction connectivity, but less is known about how surrounding circuitry shapes AII receptive fields across light levels. Here, we report that moderate contrast stimuli elicit surround inhibition in AIIs under all but the dimmest visual conditions, due to actions of horizontal cells and at least two ACs that inhibit presynaptic bipolar cells. Under photopic (daylight) conditions, surround inhibition transforms AII response kinetics, which are inherited by downstream ganglion cells. Ablating neuronal nitric oxide synthase type-1 (nNOS-1) ACs removes AII surround inhibition under mesopic (dusk/dawn), but not photopic, conditions. Our findings demonstrate how multiple layers of neural circuitry interact to encode signals across a wide physiological range. [Display omitted] • AII ("A-two") amacrine cell (AC) receptive fields (RFs) change with increasing luminance • Surround inhibition, absent in scotopic (dim light) AII RFs, emerges at higher light levels • nNOS1 ACs provide inhibitory surround to AIIs under mesopic, but not photopic, conditions • Inhibitory surround observed in some downstream ganglion cell RFs is inherited from AIIs Nath et al. show that receptive fields of AII ("A-two") amacrine cells (ACs) are shaped by strong surround suppression under mesopic and photopic conditions. Ablating nNOS1 ACs removes mesopic surround only. Changes in AII surround suppression are inherited by downstream RGCs, thereby influencing the retinal output. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]