The Research Group Molecular Imaging and Optogenetics focuses on combining state-of-the-art optogenetic techniques with optical neuroimaging.
Advancement of our understanding of neuronal network dynamics in health and disease requires the investigation of defined populations of neurons and their interactions in the intact central nervous system (CNS). Probing the specific contribution of genetically defined neuronal populations to network function is pivotal for furthering our knowledge of impairment of network dynamics and for the development of effective therapy strategies. The discovery of a rapidly gated light-sensitive cation channel channelrhodopsin-2 (ChR2) suitable for noninvasive control of neuronal activity has made it possible to optically control membrane depolarization on the millisecond timescale in genetically defined neurons. Recent developments of the optogenetic toolbox allow for the effective inhibition of genetically defined neuronal cell populations in vivo. These methods have the prospects of re-balancing disturbed neuronal circuitry by activation or inhibition of endogenous neuronal sub-circuits.
Imaging methods capable of directly mirroring neuronal activity include, among others, Ca2+ imaging using fluorescent Ca2+ indicators. The intracellular Ca2+ concentration is tightly regulated and is mainly controlled by the release and re-uptake into intracellular Ca2+ stores such as the endoplasmatic reticulum and by in- and outflux through voltage-gated Ca2+ channels in the neuronal membrane. Amplitude of intracellular Ca2+ transients in neurons is linear dependent on the number of action potentials. By using 2-photon microscopy in vivo upon bolus loading with Ca2+ indicators, the activity of small neuronal populations - micro circuits - can be monitored with cellular resolution. Combining 2-Photon imaging with optogenetics will enable the direct readout of patterns of population activity upon therapeutic intervention on circuit level.