Neurons make converging and diverging synaptic connections with distinct partner types. Whether synapses involving separate partners demonstrate similar or distinct structural motifs is not yet well understood. We thus used serial electron microscopy in mouse retina to map output synapses of cone bipolar cells (CBCs) and compare their structural arrangements across bipolar types and postsynaptic partners. Three presynaptic configurations emerge—single-ribbon, ribbonless, and multiribbon synapses. Each CBC type exploits these arrangements in a unique combination, a feature also found among rabbit ON CBCs. Though most synapses are dyads, monads and triads are also seen. Altogether, mouse CBCs exhibit at least six motifs, and each CBC type uses these in a stereotypic pattern. Moreover, synapses between CBCs and particular partner types appear biased toward certain motifs. Our observations reveal synaptic strategies that diversify the output within and across CBC types, potentially shaping the distinct functions of retinal microcircuits.
Abstract: The retinal degenerative diseases retinitis pigmentosa and age-related macular degeneration are a leading cause of irreversible vision loss. Both present with progressive photoreceptor degeneration that is further complicated by processes of retinal remodeling. In this perspective, we discuss the current state of the field of retinal remodeling and its implications for vision-restoring therapeutics currently in development. Here, we discuss the challenges and pitfalls retinal remodeling poses for each therapeutic strategy under the premise that understanding the features of retinal remodeling in totality will provide a basic framework with which therapeutics can interface. Additionally, we discuss the potential for approaching therapeutics using a combined strategy of using diffusible molecules in tandem with other vision-restoring therapeutics. We end by discussing the potential of the retina and retinal remodeling as a model system for more broadly understanding the progression of neurodegeneration across the central nervous system.
Lab Members Bryan Jones, Rebecca Pfeiffer and graduate students Megan Croom and Qwynn Landfield, and undergraduate Taylor Otterness attended this year’s annual Snowbird Neuroscience Symposium after two years of the pandemic. It was good to see people in person again, presenting their science and having an opportunity for the trainees to engage in the practice of presenting their work. Qwynn Landfield was one of the student organizers this year and asked me to provide some photographs for the program that you can see here.
We finished sectioning and capturing a massive new retinal connectome that we are going to be so excited to announce at some point in the not too distant future. Effective immediately, we are also starting on a brand new pathoconnectome that we will be powering through over the next little while. Thanks to the team of people who make this happen, shown in this post are Jia-Hui Yang, Matt Berardy, and Rebecca Pfeiffer. More photos here.
Lab PI Bryan Jones delivered a talk at the 2022 Max Planck / HHMI Connectomics Conference in Berlin, Germany yesterday. (Edit): Images from the meeting can be seen here.
Abstract: Connectomics has demonstrated that synaptic networks and their topologies are precise and directly correlate with physiology and behavior. Both chemical and electrical synapses (gap junctions) are arrayed in precise network motifs that define networks and mediate sensory percepts and influence behaviors.