Afferent input differentially regulates establishment and maintenance of synapses in the mammalian retina.

PubMed ID: 41266494

Author(s): Wallin J, Miller A, Sinha R, Hoon M. Afferent input differentially regulates establishment and maintenance of synapses in the mammalian retina. Sci Rep. 2025 Nov 20;15(1):41045. doi: 10.1038/s41598-025-25009-0. PMID 41266494

Journal: Scientific Reports, Volume 15, Issue 1, Nov 2025

How afferent input shapes synaptic connections is fundamental to our understanding of cues that govern assembly of sensory circuits. In the retina, photoreceptors provide afferent visual information to second-order bipolar cells (BCs) that in turn transfer signals to output neurons. BCs have distinct inhibitory synapses at dendrites and axons but the role of afferent input for regulating the composition and function of these synapses remains unknown. We used a photoreceptor degeneration murine transgenic with labeled BCs and combined immunohistochemical assessment of synaptic proteins across timepoints with single-cell electrophysiology and transcriptomics to address how photoreceptor input regulates BC synapses. We find that inhibitory synapses across BCs have distinct dependencies on afferent input, with axonal synapses reacting first to deafferentation even though the dendritic synapses are at the site of deafferentation. Synapses were altered in a BC-type specific manner and deafferentation differentially impacted expression of synaptic proteins vs. RNA transcripts for synaptic genes revealing disrupted synaptic trafficking pathways. Loss of afferent input also prompted production of nonfunctional receptor proteins and led to withdrawal of BC output synapses. Our findings thus reveal susceptible and resilient retinal synapse types upon deafferentation and uncover how afferent input differentially regulates synapses across second-order neurons.