The vesicle code transmitting visual information

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The fundamental function of the brain is to process information. Within neurons this information is represented by the presence or absence of a single symbol, much like zero's and one's in a computer. This symbol is an electrical pulse called a spike. But the "spike code" is only half the story because information is transmitted between neurons by pulses of chemicals called neurotransmitters. The basic symbol for this chemical code is the packet of neurotransmitter released from a neuron at a synaptic connection but, compared to our understanding of the spike code, we have very little understanding of the vesicle code.It has been assumed that synapses represent information by releasing individual vesicles independently, with more being released to signify a larger quantity such as a stronger stimulus. We recently used advanced optical microscopes to isolate the signals from individual excitatory synapses in the retina of live zebrafish as they responded to visual stimuli and this provided a new picture. Some synapses in the retina use not just two symbols, but up to ten or eleven, comprised of one, two, three or more vesicles released as a single event. This process, termed multivesicular release, is a feature of synaptic connections in many brain regions but it's role in information processing is not known. This proposal uses zebrafish to build from this work and analyze the vesicle code transferring information at the first three synaptic stages of vision, from the retina to downstream circuits. Our central hypothesis is that all the synapses in early vision are capable of encoding information as changes in both the rate and amplitude of synaptic events but to varying degrees, depending on the structure of the synapse and the information transmitted by the neuron.We will investigate this hypothesis through three overlapping questions: Aim 1. How is visual information transmitted from the photoreceptors? At the input to the retinal circuit, photoreceptors encode visual stimuli as graded ("analogue") changes in membrane potential and these are recoded through "ribbon" synapses specialized for transmitting the first visual signals. We will test the hypothesis that photoreceptor synapses increase the reliability of the visual signals by acting as a "clock" that reduces the variability of the signal transmitted.Aim 2. How much visual information is lost in bipolar cells? By the time the visual signal reaches the output neurons of the retina (RGCs), it has been converted into the digital form of spikes. This process is fundamental to visual processing and is often assumed to occur in RGCs, but we have shown that it can begin within the synapse of bipolar cells, the neurons that connect photoreceptors to RGCs. BCs act as an information bottleneck and also transmit signals through "ribbon" synapses, although with structures distinct from those in photoreceptors. We will test the hypothesis that different BCs transmit different amount of information depending on their functional role. Aim 3. How much information does the fish's eye send to the fish's brain? The retina decompose the visual input into areas of bright and dark, objects of different size or orientation, moving at different speeds and in different directions. These different aspects of the visual input are streamed to different parts of the brain through different RGCs. Many RGCs send signals to more than one target circuit but we do not know if they send the same message . We now need to understand how much visual information can be transmitted through conventional synapses and how efficiently they use synaptic vesicles. We will test the hypothesis that individual RGCs employ MVR to differing degrees to transmit different amounts of information to different targets.By focusing on vision, this project will help us understand the most fundamental function of synapses in the brain - the transfer of information.