Abstract
The causal analysis of neuronal network function requires selective manipulations of genetically defined neuronal subpopulations in the intact living brain. Here, we highlight the method of optogenetics, which meets those needs. We cover methodological aspects, limitations, and practical applications in the field of neurosciences. The fundamentals of optogenetics are light-sensitive transmembrane channels and light-driven ion pumps, which can be genetically encoded, without requiring the application of exogenous cofactors. These opsins are expressed in neurons by means of viral gene transfer and cell-specific promoters. Light for stimulation can be non- or minimally invasively delivered by optical fibers. Illumination of opsins results in a depolarization or hyperpolarization of genetically modified neurons, depending on the type of optogenetic actuator. Strong expression levels and sufficient light densities provided, neuronal activity can be optically controlled in the intact network with millisecond precision. By applying fluorescent indicators of neuronal activity, an all-optical neurophysiological approach becomes reality.
About the authors
1994-1996 Studies in Biology, Free University Berlin; 1996-2001 Studies in Biophysics, Humboldt University Berlin; 2002-2005 PhD student, Charité Berlin, Neuroradiology/Neurology; topic: Cellular Magnetic Resonance Imaging of magnetically labeled stem cells in rodent models of neurodegenerative CNS diseases; 2006-2007 Postdoctoral fellow with Karl Deisseroth, Stanford University; topic: Causal analysis of neuronal differentiation of stem cells by optogenetics; 2007-2012 Postdoctoral fellow with Arthur Konnerth, Technical University Munich; topic: Combining optogenetics and Ca2+imaging for probing thalamo-cortical oscillations; since 2012 W1-professor for optogenetics and molecular imaging, Focus Group Translational Neurosciences, Institute for Microscopic Anatomy and Neurobiology, University Mainz; topic: Applying optogenetics in combination with 2-photon Ca2+imaging for the analysis of neuronal network function in vivo.
1998-2003 Studies in Biology, Humboldt University Berlin; 2003-2008 PhD student, Hertie Institute for Clinical Brain Research, Tübingen; topic: Neural correlates of numerical competence in non-human primates; 2008-2011 Postdoctoral fellow with Karl Deisseroth and Krishna Shenoy, Stanford University; topic: Optogenetics in non-human primates; since 2011 Research Group Leader at the Ernst-Strüngmann-Institute for Neuroscience in Cooperation with Max Planck Society; topic: Sensory-motor circuits and optogenetics.
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