The first synapse in vision in the aging mouse retina

Vision is our primary sense, and maintaining it throughout our lifespan is crucial for our well-being. However, the retina, which initiates vision, suffers from an age-related, irreversible functional decline. What causes this functional decline, and how it might be treated, is still unclear. Synapses are the functional hub for signal transmission between neurons, and studies have shown that aging is widely associated with synaptic dysfunction. In this study, we examined the first synapse of the visual system – the rod and cone photoreceptor ribbon synapse – in the mouse retina using light and electron microscopy at 2–3 months, ~1 year, and >2 years of age. We asked, whether age-related changes in key synaptic components might be a driver of synaptic dysfunction and ultimately age-related functional decline during normal aging. We found sprouting of horizontal and bipolar cells, formation of ectopic photoreceptor ribbon synapses, and a decrease in the number of rod photoreceptors and photoreceptor ribbon synapses in the aged retina. However, the majority of the photoreceptors did not show obvious changes in the structural components and protein composition of their ribbon synapses. Noteworthy is the increase in mitochondrial size in rod photoreceptor terminals in the aged retina

Angiotensin-Receptor-Associated Protein Modulates Ca2+ Signals in Photoreceptor and Mossy Fiber cells

Fast, precise and sustained neurotransmission requires graded Ca2+ signals at the presynaptic terminal. Neurotransmitter release depends on a complex interplay of Ca2+ fluxes and Ca2+ buffering in the presynaptic terminal that is not fully understood. Here, we show that the angiotensin-receptor-associated protein (ATRAP) localizes to synaptic terminals throughout the central nervous system. In the retinal photoreceptor synapse and the cerebellar mossy fiber-granule cell synapse, we find that ATRAP is involved in the generation of depolarization-evoked synaptic Ca2+ transients. Compared to wild type, Ca2+ imaging in acutely isolated preparations of the retina and the cerebellum from ATRAP knockout mice reveals a significant reduction of the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity. Thus, in addition to its conventional role in angiotensin signaling, ATRAP also modulates presynaptic Ca2+ signaling within the central nervous system