Start of funding 01.01.2011

Development of optogenetic and optopharmacological tools to study central nervous plasticity

Prof. Dr. Hans Straka
Ludwig-Maximilians-University of Munich

Prof. Sascha du Lac
University of California, San Diego
Salk Institute for Biological Sciences



The current project combines the expertise of two research groups at the LMU Munich and the Salk Institute in La Jolla to develop cutting-edge technologies in the field of light-activated molecules and optogenetic/optopharmaco¬logical tools for individualized modulation of neural activity in the brain. The goal is implementation and refinement of these innovative methodologies to facilitate physiological studies. The newly available tools are based on combined molecular and optic technologies that allow light-activated manipulation of neural discharge. A major challenge is the specific insertion of optogenetic molecules (mRNA-Plasmids) such as channelrhodopsin or halorhodopsin into particular neuronal populations by electroporation/transfection to modulate the activity after photochemical internalization into the membrane. Specific injection of the substances into vestibulo-motor and cerebellar areas in mouse and Xenopus allows perturbation of sensory-motor processing to study particular aspects of neural plasticity and motor learning.

Final report:
Based on reciprocal visits of members of the two research groups at the LMU Munich and the Salk Institute in La Jolla, we have developed and established optical evaluation methods and installed the respective microscopes to study neuronal plasticity. These setups allow optical uncaging of transmitter candidates in the brain of Xenopus frogs (LMU Munich) and optical activation of neurons in the cerebellum of mice (Salk Institute). The novel installations along with the establishment of semi-intact preparations of Xenopus and functional calcium-imaging in Munich were used to record sensory evoked neuronal responses in central vestibular neurons. For quantification of the glutamate uncaging efficiency the required light intensity and duration to optically evoked action potentials was calculated by simultaneous patch-clamp recordings. By spatially separating calcium imaging and glutamate uncaging it was possible to manipulate ipsilateral semicircular canal evoked calcium responses by optically activating contralateral inhibitory/excitatory pathways. Using different mouse-lines that express light-activated channelrhodopsin in cerebellar neurons at the Salk institute it was possible to evoke directionally specific eye movements after optical activation of the respective cerebellar structures. The results of these proof-of-principle experiments in both laboratories are currently being completed and prepared for publication.