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switchBoard Report Summary

Project ID: 674901
Funded under: H2020-EU.1.3.1.

Periodic Reporting for period 1 - switchBoard (In the eye of the observer: Visual processing at the heart of the retina)

Reporting period: 2015-11-01 to 2017-10-31

Summary of the context and overall objectives of the project

Parallel information processing in the visual system starts to emerge already in the eye. Here, the retina, which is ontologically a part of the brain, represents the first outpost of visual processing. In contrast to other senses, where the sensory cells are “wired” more or less directly to neurons that project to the brain, the retina contains an additional layer of interneurons. These interneurons heavily process the light signal from the photoreceptors before it is passed onto the retinal ganglion cells (RGCs) – the retina’s output neurons – and forwarded via the optic nerve to higher visual centres in the brain.
At first glance, the organisation of the retina looks simple: An excitatory, “vertical” signal pathway links the photoreceptors via the bipolar cells (BCs, a class of interneurons) to the RGCs. Signals along this vertical pathway are shaped by lateral, inhibitory interactions with two more classes of interneurons, the horizontal cells (HCs) and the amacrine cells (ACs). A first glimpse at the actual complexity of mammalian retinal signal processing offers the number of neuron types present: the signals from 3-4 types of photoreceptors – modulated by usually 2 types of HC in the outer retina – is distributed onto more than a dozen BC types, indicating that parallelisation of visual information already starts at the first synapse of the visual system. In the inner retina, the BC signals are picked up by the dendritic arbours of around 40 types of RGCs. Moreover, at least a similarly high number of AC types shape the signal flow from BCs to RGCs via highly selective synaptic interactions. Finally, each RGC type relays a separate “view” of the visual scene to higher areas in the brain.
At the heart of retinal signal processing lies a thick and dense synaptic layer. Here, the axon terminals of BCs interact with the dendrites of ACs and RGCs. Because of its layered structure and highly selective connectivity, it is reminiscent of an old-style electric switchboard for managing phone connections – hence the name of the consortium. BCs are an excellent starting point for unrevealing key principles of parallel processing in the visual system: First, they represent the first stage of signal parallelisation in the visual system, and second, they are the “motor” that drives the generation of feature representations in the inner retina, thereby forming the basis for the next, much larger set of parallel information channels represented by the RGCs. Third, with “only” around 15 types, the BC class is sufficiently diverse while still experimentally well approachable.
The overall scientific objective of the switchBoard consortium is an in-depth understanding of the BCs as an entire neuron class and of their role in the first critical steps of vision. The consortium combines expertise in neuroscience and vision research, together with an exceptionally broad spectrum of methods available in the partners’ labs, holding the exciting promise that this goal is within reach.
switchBoard’s scientific objectives go hand in hand with its main training goal: To prepare early stage researchers (ESRs) for a successful career in a quickly changing research field. For ESRs, the interdisciplinarity of neuroscience is attractive, with career paths in both the public and private sector. Also, for a successful neuroscience career, ESRs must be trained in more than one field. Consequently, switchBoard ensures that ESRs receive in-depth training in experimental and computational neuroscience, neurotechnology, and biomedicine. To this end, the consortium implements an intense training programme, complemented by hand-on workshops organised by our partners from industry. Through its research and training program, switchBoard contributes to replenishing resources that, while often taken for granted, are of paramount importance for Europe: by training the next generation of competitive, multidisciplinary young scient

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The overall goal of work package (WP) 1 is the generation of a rich dataset that contains detailed morphological and functional information about BCs and their synaptic interactions. The data collected so far highlight the complexity of BC circuits, e.g. with respect to electrical synapses to ACs or the precise control of transmitter release from BC terminals. These data on BC morphology, connectivity and physiology acquired so far now serve as a starting point for building biophysically realistic, compartmental bipolar cell models (jointly with WP3). WP2 investigates how retinal diseases alter BC function and, con¬secutively, the retinal network. First results suggest a more severe degree of degeneration-induced inner retinal remodelling than previously expected, with BCs playing a central role in mediating aberrant spontaneous activity. WP3 develops computational models of BC function and new research technologies. The modelling projects address different complexity levels and use very different approaches. For example, one biophysically realistic bottom-up model already successfully simulates BC responses to electric fields, mimicking the effects of stimulation by a retinal implant. The technology-oriented projects focus on developing new methods – to measure neuronal activity in retina and eye using high resolution electrode arrays or digital mirror devices – or work on improving retina-inspired cameras by adding image-decoding principles implemented by BC circuits in the biological retina.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In the second reporting period, it is planned that modelling efforts in WP1 and WP3 will grow closer together, providing all models with data collected in the switchBoard network and funnelling the insights gained by the modellers back to the experimenters. The close interaction between computational and experimental neuroscientists is a long-standing goal in the neuroscience community. Here, within the switchBoard network with its expertise in both fields, there is a realistic chance for such powerful joint-ventures to happen.
The results of WP2 so far strengthen the view that BCs not only are in a key position for diverse vision rescue approaches but may also be critically involved in generating and/or relaying aberrant activity that limits the effectiveness of rescue approaches. We expect this important result to be corroborated and generalised across the studied mouse models for retinal degeneration. Furthermore, we expect a better understanding of the underlying mechanisms – knowledge that is instrumental for devising treatments to prevent or postpone remodelling and, thus, aberrant activity.
Understanding of neuronal function promises new insights for the design of technological solutions in information processing. Specifically, we expect the insights from the top-down model in WP3 to inspire improvements of the “silicon retina”, a retina-inspired camera system. The suggested improvements are revolving around the encoding of spatio-temporal information; this is an interesting finding, because encoding spatio-temporal information appears to be exactly what BC circuits are made for.
Potential applications aside, including a method- and technology-oriented WP into the training network turned out to be quite useful to encourage the ESRs from other WPs to look beyond biology and explore the possibilities of a non-academic career in methods development and neurotechnology.
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