Euler Lab

Ophthalmic Research

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Introduction

Visual information processing begins in the retina, a thin neuronal tissue lining the back of the eyeball. As a part of the brain, the retina does not only convert the incoming stream of photons into electrical signals, it also performs a detailed and highly specific analysis of the observed scene. Therefore, the retina can be considered a highly specialized and sophisticated image processor.

All visual information sent from the retina to the brain travels along the optic nerve, a major bottleneck of the visual system. Therefore, prior to transmission to the brain, important aspects of the observed scene must be extracted and encoded as spike patterns. These features include simple ones such as contrast, brightness, and “colour”, but also more complex ones, such as information about objects moving relative to the background. Thus, the retina sends in parallel many representations of the visual scene to the brain; each of these representations encodes different features and is represented by one of the roughly 40 retinal ganglion cell types whose axon form the optic nerve. The importance of retinal signal processing is highlighted by the fact that important decisions – what visual information is relevant, and what can be safely discarded – is made already in the retina.

The computational capabilities of this intricate neuronal network rely on more than 100 types of retinal neurons organized in complex microcircuits. Our work aims at unravelling function and organization of retinal microcircuits towards a better understanding of the underlying computational principles. Furthermore, we are interested in how these circuits are altered during degeneration.

Methods

We established a comprehensive method catalogue for optical measurements of light-driven population activity along the retina’s entire vertical pathway based on synthetic and genetically encoded fluorescent activity sensors.

Our key technique is two-photon (2P) microscopy, which enables us to excite fluorescent probes in the intact living retinal tissue using infrared laser light, with minimal effects on the light-sensitive photoreceptor pigment. Therefore, we can simultaneously record activity in neurons at both population and subcellular levels while presenting sophisticated light stimuli.

In addition, we develop new methods for 2P imaging – specifically in the retina – as well as open source/hardware tools for visual stimulation.

A: Ganglion cell layer of a mouse retina in top view: the colours indicate different functionally defined ganglion cell types (top). Below, the same region of the retina is shown as seen in the two-photon microscope, when cells have been “stained” with a fluorescent activity indicator. B: Light responses of more than 11,000 cells; each block indicates a ganglion cell type (red: high activity, blue: low activity). The ganglion cell layer includes also somata of amacrine cells, making up for about 1/3 of the total number of cells. C: Light responses (top left), soma distribution (top right) as well as morphology in top view (bottom left) and vertical section (bottom right) of two types of ganglion cell: transient Off alpha cells respond to any contrast change in their receptive field, while On-Off “W3” cells prefer small dark objects moving in the upper visual field. D: Mosaic of the two ganglion cell types (from C) in top view. The gaps at the boarders are caused by cells with the cell body outside of the reconstructed piece of tissue. Modified figures in A-C with permission from (Baden et al., 2016); Figure in D from museum.eyewire.org with permission from S. Seung). Figure adapted from Berens & Euler (2017)

The imaging approach is complemented by single-cell electrophysiology and immunocytochemistry, as well as large-scale data analysis in close collaboration with the groups of Philipp Berens, Matthias Bethge, and Katrin Franke at Tübingen University.

Example: Rendering of a 4-spectral channel R-G-B-UV zebrafish stimulator developed in collaboration with the groups of Katrin Franke and Tom Baden. For details see project repository and Franke et al. 2019. Rendering by MJY Zimmermann.

Research Questions

Local circuits
How do individual neurons at different stages of the retinal network process information in their dendrites and/or axon terminal systems?

The retinal code
How are the numerous parallel output channels that are present at the level of the ganglion cells set up in the retinal network? What visual features are encoded in these channels?

Visual ecology
To what extent is the mouse retina adapted to the animal’s natural visual habitat? What functional roles do retinal specializations - such as the opsin expression gradient - fulfil in this context?

Health and disease
How does the retinal network rewire and alter its function when photoreceptors degenerate?

Reproducible science

We believe that the best way to achieve reproducible scientific results is to promote open science, including sharing data and making software for scientific research freely available.

Collaborations

  • Tom Baden
    University of Sussex, Brighton, UK
  • Philipp Berens
    Institute for Ophthalmic Research, University of Tübingen, Germany
  • Matthias Bethge
    CIN / Institute for Theoretical Physics / BCCN, University of Tübingen, Germany
  • Laura Busse
    LMU Munich, Germany
  • Kevin Briggman
    Caesar, Bonn, Germany
  • Karin Dedek
    Dept. of Neurobiology, University of Oldenburg, Germany
  • Katrin Franke
    BCCN / MPI biol. Cybernetics / Institute of Ophthalmic Research, University of Tübingen, Germany
  • Silke Haverkamp
    Caesar, Bonn, Germany
  • Andrew Huberman
    Dept. of Neurobiology, Stanford University School of Medicine, CA, USA
  • Markus Meister
    Caltech, Pasadena, CA, USA
  • Sebastian Seung
    Princeton Neuroscience Institute and Computer Science Dept., Princeton, NJ, USA
  • Robert Smith
    Dept. of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA
  • W. Rowland Taylor
    University of California  Berkeley, CA, USA
  • Rachel O. Wong
    Dept. of Biological Structure, University of Washington, WA, USA