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Towards a complete representation of visual information at a single retinal location

Color-coded activity in ganglion cells of the mouse retina. By T. Baden

Right at the first synapse of the mammalian retina, the stream of incoming visual information is split into several parallel information channels represented by different kinds of retinal ganglion cells (RGCs). About 20 different morphological RGC types have been described and each population tiles the retinal surface with their dendritic arbours. Both our understanding of the functions represented by the different RGC types and the underlying feature-extracting microcircuits is still incomplete; however, from a wealth of earlier work we know that morphologically distinct types of retinal neurons usually also have specific functions. The goal of this project is to simultaneously record from all RGC types at one retinal location using two-photon imaging to obtain a complete sample of the information sent to the brain and to understand how the representation of spatio-temporal information in a local image patch is distributed across the set of RGC types.

We have developed a battery of visual stimuli towards a physiological characterization of all cells in the ganglion cell layer (GCL) in an image patch. Currently, our database contains >10,000 GCL cells from >30 retinas. Out of those, the best responding cells were used as the input to our Mixture of Gaussians Clustering model. Based on their responses to our light stimulus set, we can distinguish between 15 and 20 retinal ganglion cell clusters, several of which are readily matched to known morphological/genetic types. We also find a number of amacrine cell clusters that roughly matches the number of types predicted by anatomy.  

Left: Whole-mount view of a calcium indicator-stained mouse retina, with the cells in the central patch color-coded by cluster affiliation (see centre panel). Centre: Retinal ganglion cell (RGC) responses to different visual stimuli sorted by functional cluster RGC clusters. Right: Distribution and morphology of the two example RGCs highlighted in the centre panel.

We currently refine our clustering algorithm and are in the process of adding data from transgenic animals as well as further immuno data to verify the clustering and to link clusters to known morphologically and genetically identified cell types. Moreover, we continue to collect single unit extracellular recordings followed by intracellular filling of individual RGCs to generate the link between functional clusters, spike output and cell morphology.

Following our group’s large scale surveys of the functional channels represented by mouse cone-photoreceptors (Baden, Schubert et al., Neuron in press), bipolar cells (Baden et al., Curr Biol 2013) and DSGCs (Auferkorte et al., PLoS One 2011), this collaborative study is aimed to complement a complete functional survey of the retina’s vertical pathways.

Involved Scientists:Tom Baden, Katrin Franke, Miroslav Román Rosón, in collaboration with Matthias Bethge and Philipp Berens (Computational Neuroscience, CIN).