Retinal Curcuits and Optogenetics

Relations Between Neural Circuits and their Functions

We use the mammalian retina as a model system to explore how the structure of neural circuits and their function are interrelated. Our work has two major focus areas. First, we study the healthy retina, and explore structure and connectivity of retinal circuits that allow complex imaging computations to be peformed. Second, we use the retinas of animals affected by blindness to explore novel genetic tools to restore the function of the retina after retinal degeneration. Our group is also member of the Bernstein Center for Computational Neuroscience Tübingen. Our methodologies span a wide range covering molecular biology, genetics, electrophysiology, imaging, histology, and behavioral experiments.

Projects

Restoration of Retinal Function in Blindness

In retinal degeneration, the gradual death of photoreceptors leads to blindness. There is no known treatment. We investigate optogenetic tools to restore visual function. We express genetically encoded optical neuromodulators (e.g. channelrhodopsin-2) in the remaining retinal neurons of degenerate retina. We quantify the success of vision restoration on the level of retinal morphology and physiology, and on the behavioral level of the animals treated. Our main focus is on the optimization of the optogenetic treatment strategy for different inherited forms of retinal degeneration.

Influence of adaptation on retinal function

The retina functions over light intensities spanning 14 orders of magnitude. We are interested in how the function of individual retinal circuits changes (or doesn't change) with the change of the ambient light level.

The role of calcium channel subunits

α2δ is an accessory subunit of voltage-gated calcium channels. Mutations of these proteins lead to retinal degeneration in mice and humans. We study the role of these proteins in the retina, and investigate how the mutations cause the disease phenotype. Such mutations also lead to defects in the auditory system. We therefore collaborate closely with Prof. Marlies Knipper (Hearing Research Center, Tübingen) and Prof. Jutta Engel (Saarland University), who study the function of α2δ in the auditory system.

Interaction of retinal ganglion cells with glia cells

In collaboration with Maria Kukley, we study the interaction of ganglion cell axons within the optic nerve with oligodendrocyte precursor cells during development. We investigate if neural-glial interactions influence the myelination of ganglion cell axons in a cell-type specific way.

Development of novel functional imaging tools

In collaboration with Prof. Robert Feil (Interfacultative Institute for Biochemistry) we test novel biosensors for functional imaging of neurons. Currently, we test indicators for the second messenger molecule cGMP.

Physiology of the larval phototactic response of a marine polychaete, Platynereis dumerilii

In collaboration with Gáspár Jékely (MPI for Developmental Biology) we are establishing an in-vivo electrophysiology recording system to study the responses of all cellular elements involved in the phototatic response of the larvae of Platynereis dumerilii. These elements include the photoreceptors of the simple larval eyes, and the ciliated cells that are responsible for the locomotion.