PubMed ID: 42715077
Author(s): Schultz A, Zhai H, Chu Y, Venkit P, Hoon M, Sinha R. A multifaceted role for synaptic ribbons in sensory circuit assembly and computation. Proc Natl Acad Sci U S A. 2026 Sep 15;123(37):e2611577123. doi: 10.1073/pnas.2611577123. Epub 2026 Sep 9. PMID 42715077
Journal: Proceedings Of The National Academy Of Sciences Of The United States Of America, Volume 123, Issue 37, Sep 2026
Computations in sensory circuits rely on specialized synapses. In photoreceptors and retinal second-order bipolar neurons, light modulates continuous neurotransmitter release from a ribbon, a large planar structure at the synaptic release site. How ribbons regulate retinal circuit assembly and shape spatiotemporal coding properties of neural circuits remains unclear. Using a combinatorial structure-function analysis in a ribbon loss-of-function mouse model, we reveal that ribbons are required for proper organization and partner connectivity at photoreceptor synapses and for accruing of synaptic proteins at inner retinal synapses. Lack of synaptic ribbons leads to an enlargement of the dendritic field size of the retinal second-order neurons, bipolar cells, which alters spatial encoding for a key retinal circuit, ONα ganglion cell. We further demonstrate that such structural alterations of synapses in the absence of ribbons impact both tonic and light-evoked neurotransmitter release as well as recovery of synapse function after depression. These perturbations in synaptic structure and function in the absence of ribbons lead to alterations in salient visual computations such as light adaptation, receptive field organization, and feature detection across time and space in the ONα ganglion cell circuit. We further reveal that a lack of ribbons impairs the encoding of naturalistic changes in visual contrast and luminance for this retinal circuit. Our findings thus reveal synaptic ribbons to be core determinants of the mammalian retina, acting not only as neurotransmitter release machines but also as organizers of circuit assembly and regulators of visual encoding.