Wie die Antwortvielfalt retinaler Ganglienzellen aus den synaptischen Interaktionen in der inneren Retina entsteht - ein Ansatz basierend auf 2-Photonen-Populationsaufnahmen und statistischer Modellierung

• Antragsteller: Professor Dr. Philipp Berens, seit 6/2016
• Fachliche Zuordnung: Kognitive, systemische und Verhaltensneurobiologie ; Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2014 bis 2017
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 260009071

• Erstellungsjahr: 2018

Zusammenfassung der Projektergebnisse

We set out to establish how visual patterns of light falling into the eye are picked up and processed by the neurons of the retina before prior to transmission to the brain via the optic nerve. For this, we focused on the neurons of the inner retina. Here, functionally distinct types of bipolar cells and retinal ganglion cells interconnect with inhibitory circuits to extract and highlight visual information of key importance for vision. For example, one set of neurons might be particularly responsive to the beginning of a light stimulus, while another set might in parallel inform about its end. The complexity of such “visual features” can also be much more complex: some neurons specifically respond to motion, the orientation of an edge, or the colour-content of an object. To capture a large fraction of visual features detected by retinal neurons at this level, we used noninvasive 2-photon imaging to record from large numbers of neurons in the intact retina of mice and presented a broad range of generic stimuli. This allowed us to segregate different neuronal response types and thereby assign specific functions to specific neurons in a high-throughput and unbiased manner. The result is a comprehensive overview of how all bipolar cells and ganglion cells of the mouse retina pick apart the visual input into multiple parallel representations. One key result was that the number of these parallel representations far exceeded previous estimates, highlighting that what the “mouse’s eye tells the mouse’s brain” is much more complex than previously thought. Another major finding is that inhibitory circuits systematically diversify the way that bipolar cells respond to visual stimuli. We are currently studying how these signals provided by the bipolar cells are integrated along the dendrites of the ganglion cells. In parallel, we also established anatomical connectivity rules and functional profiles of neurons in the mouse outer retina and published several method papers associated with this work. Most recently, we started to develop a comparative perspective on the visual response properties of retinal neurons and surveyed function of inner retinal neurons in the zebrafish. These were quite distinct from those found in mice. In summary, the project successfully established functional fingerprints of retinal bipolar cells in mice and has started to tease apart the dendritic computations by which the cellular signals are recombined in ganglion cells.

Projektbezogene Publikationen (Auswahl)

• (2017) Connectomics of synaptic microcircuits: lessons from the outer retina. The Journal of physiology 595 (16) 5517–5524
  Rogerson, L. E., Behrens, C., Euler, T., Berens, P., & Schubert, T.
  
• (2017). Community-based benchmarking improves spike inference from two-photon calcium imaging data
  Berens, P., Freeman, J., Deneux, T., Chenkov, N., McColgan, T., Speiser, A., ... & Bethge, M.
  
• (2015). Open Labware: 3-D Printing Your Own Lab Equipment. PLoS Biology 13(3): e1002086
  Baden, T., Chagas, A. M., Gage, G., Marzullo, T., Prieto-Godino, L. L., Euler, T.
  
• (2016). Benchmarking spike rate inference in population calcium imaging. Neuron, 90(3), 471-482
  Theis, L., Berens, P., Froudarakis, E., Reimer, J., Rosón, M. R., Baden, T., ... & Bethge, M.
  
• (2016). Connectivity map of bipolar cells and photoreceptors in the mouse retina. Elife, 5
  Behrens, C., Schubert, T., Haverkamp, S., Euler, T., & Berens, P.
  
• (2016). The functional diversity of retinal ganglion cells in the mouse. Nature, 529(7586), 345-350
  Baden, T., Berens, P., Franke, K., Rosón, M. R., Bethge, M., & Euler, T.
  
• (2017) The €100 lab: A 3D printable open source platform for fluorescence microscopy. Optogenetics, and accurate temperature control during behaviour of zebrafish, Drosophila and Caenorhabditis elegans. PloS Biol. 15(7): e2002702
  Chagas, A. M., Prieto Godino, L. L., Arrenberg, A. B., Baden, T.
  
• (2017). Inhibition decorrelates visual feature representations in the inner retina. Nature, 542(7642), 439-444
  Franke, K., Berens, P., Schubert, T., Bethge, M., Euler, T., & Baden, T.
  
• (2017). Local Signals in Mouse Horizontal Cell Dendrites. Current Biology, 27(23), 3603-3615
  Chapot, C. A., Behrens, C., Rogerson, L. E., Baden, T., Pop, S., Berens, P., Euler, T. & Schubert, T.
  
• (2017). Signatures of criticality arise from random subsampling in simple population models. PLoS Computational Biology, 13(10), e1005718
  Nonnenmacher, M., Behrens, C., Berens, P., Bethge, M., & Macke, J. H.
  
• (2017). Zebrafish differentially process colour across visual space to match natural scenes
  Zimmermann, M. J. Y., Nevala, N. E., Yosimatsu, T., Osorio, D., Nilsson, D. E., Berens, P., Baden, T.