Synaptic transmission at retinal ribbon synapses

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In sensory cells of the eye and inner ear the neurotransmitter glutamate is released at active zones in a graded and continuous manner. These cells have evolved specialized structures known as synaptic ribbons. These proteinaceous structures tether synaptic vesicles near active zones. Based on their location, abundance of tethered vesicles, and properties of the sensory neurons in which they are found, these organelles have long been thought to be important for maintaining the continuous release of glutamate. Several other functions have also been ascribed to ribbons. However, recent evidence casts doubt on these ideas. The focus of this grant is to understand the role of synaptic ribbons in sensory synaptic transmission using animal models that lack Ribeye, a protein that is both the most abundant within the ribbon and not found anywhere else. Lack of Ribeye leads to loss of membrane associated synaptic ribbons, without loss of other presynaptic proteins. Specific Aim 1 investigates how Ribeye removal and loss of synaptic ribbons affects neurotransmitter release from photoreceptors. Specific Aim 2 looks at the properties of synaptic release in bipolar cells from the same animals. In Specific Aim 3, we will image single synaptic vesicles in cells lacking Ribeye to measure rates of vesicle movement and replenishment to test the role of the ribbon in these processes. Understanding ribbon function may provide clues to help understand diseases that specifically affect vision and hearing. In addition, the fundamental understanding of presynaptic processes in these specialized neurons will have broader implications for neuronal communication in general and thus, may contribute to our understanding of various aspects of mental health and neurological disorders.