Die zelluläre und molekulare Grundlage des Bewegungssehens

• Antragstellerin: Professorin Dr. Marion Silies
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2014 bis 2022
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 246609904

• Erstellungsjahr: 2023

Zusammenfassung der Projektergebnisse

Many animals use visual cues, and especially motion cues, to navigate the world. Motion detection is a thus behaviorally relevant computation, whose hallmark is the emergence of direction-selective signal in visual circuitry. To become direction selective, neural circuits have to compare light signals over space and time. In my Emmy Noether project, I proposed to use Drosophila melanogaster as a model system to identify the molecular, cellular and circuit mechanisms of motion detection, linking molecular mechanisms to circuit function and behavior. At the start of the project, we knew that lamina neurons L1, L2 and L3 feed into motion-detection circuits, and that T4/T5 are the first direction-selective cells in the fly visual pathways. The interneurons were not known. Using a behavioral screen, we identified the Tm9 interneuron that connects L3 neurons to T5 DS-cells in the OFF pathway. In parallel, other groups identified other medulla interneurons mostly based on connectomics studies. Together, we now have a good understanding of core visual circuits in the fly. We next asked what molecular mechanisms confer distinct physiological properties to identified visual cell types. Starting in the lamina, we showed that differential expression of voltage-gated potassium channels shapes lamina neuron responses. In ongoing work, we also identified a transcription factor and its downstream targets to differentiate L2 from L3 function (Sporar et al., in preparation). One synapse downstream of the lamina, medulla neurons become either ON or OFF selective. We worked out the molecular and circuit basis of the emergence of ON selectivity. This requires a sign inversion and rectification of the presynaptic lamina neuron input, which relies on inhibition through both glutamatergic and GABAegic chloride channels. The physiological and behavioral characterization of the L3-Tm9 pathway suggested a more general role in visual processing. We showed that the L3 cell types preserves luminance information postsynaptic to photoreceptors. This luminance information is required for rapid luminance gain control that acts at timescales fast than photoreceptor adaptation. This luminance gain control extends across both ON and OFF visual pathways. Together, our work provided fundamentally new insights in the molecular circuit mechansms of motion computation, and of peripheral visual processing strategies in general.

Projektbezogene Publikationen (Auswahl)

• A Class of Visual Neurons with Wide-Field Properties Is Required for Local Motion Detection. Current Biology, 25(24), 3178-3189.
  Fisher, Yvette E.; Leong, Jonathan C.S.; Sporar, Katja; Ketkar, Madhura D.; Gohl, Daryl M.; Clandinin, Thomas R. & Silies, Marion
  
• Molecular Remodeling of the Presynaptic Active Zone of Drosophila Photoreceptors via Activity-Dependent Feedback. Neuron, 86(3), 711-725.
  Sugie, Atsushi; Hakeda-Suzuki, Satoko; Suzuki, Emiko; Silies, Marion; Shimozono, Mai; Möhl, Christoph; Suzuki, Takashi & Tavosanis, Gaia
  
• Different modes of APC/C activation control growth and neuron-glia interaction in the developing Drosophila eye. Development, 144(24), 4673-4683.
  Neuert, Helen; Yuva-Aydemir, Yeliz; Silies, Marion & Klämbt, Christian
  
• Motion detection: cells, circuits and algorithms. Neuroforum, 24(2), A61-A72.
  Ramos-Traslosheros, Giordano; Henning, Miriam & Silies, Marion
  
• Distinct expression of potassium channels regulates visual response properties of lamina neurons in Drosophila melanogaster. Journal of Comparative Physiology A, 206(2), 273-287.
  Gür, Burak; Sporar, Katja; Lopez-Behling, Anne & Silies, Marion
  
• ON selectivity in the Drosophila visual system is a multisynaptic process involving both glutamatergic and GABAergic inhibition. eLife, 8.
  Molina-Obando, Sebastian; Vargas-Fique, Juan Felipe; Henning, Miriam; Gür, Burak; Schladt, T Moritz; Akhtar, Junaid; Berger, Thomas K & Silies, Marion
  
• Luminance Information Is Required for the Accurate Estimation of Contrast in Rapidly Changing Visual Contexts. Current Biology, 30(4), 657-669.e4.
  Ketkar, Madhura D.; Sporar, Katja; Gür, Burak; Ramos-Traslosheros, Giordano; Seifert, Marvin & Silies, Marion
  
• m6A RNA methylation regulates promoter- proximal pausing of RNA polymerase II. Molecular Cell, 81(16), 3356-3367.e6.
  Akhtar, Junaid; Renaud, Yoan; Albrecht, Steffen; Ghavi-Helm, Yad; Roignant, Jean-Yves; Silies, Marion & Junion, Guillaume
  
• First-order visual interneurons distribute distinct contrast and luminance information across ON and OFF pathways to achieve stable behavior. eLife, 11.
  Ketkar, Madhura D.; Gür, Burak; Molina-Obando, Sebastian; Ioannidou, Maria; Martelli, Carlotta & Silies, Marion