
Optogenetics
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Optogenetics combines genetic engineering with optics to observe and control the function of cells using light, with clinical implications for restoration of vision and treatment of neurological diseases. As a new discipline much of the basic science and methods are currently under investigation and active development, thus there is a strong need for introductory literature in this field. This graduate level textbook provides an overview of the field of optogenetics in 5 concise chapters: Optogenetic tools, Applications in cellular systems, Mapping neuronal networks, Clinical applications and Restoration of vision and hearing. The concept and content was developed with top international researchers and students at a prestigious Dahlem Conference workshop.
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Content
- Intro
- List of contributing authors
- Introduction
- 1 The biophysics and engineering of signaling photoreceptors
- 1.1 Photoreceptors
- 1.1.1 Novel photoreceptors
- 1.1.2 Biophysics of photoreceptors and signal transduction
- 1.2 Engineering of photoreceptors
- 1.2.1 Approaches to designing light-regulated biological processes
- 1.3 Case study - transcriptional control in cells by light
- 1.4 Conclusion
- Acknowledgements
- References
- 2 Current challenges in optogenetics
- 2.1 Introduction
- 2.2 Background: current functionality of tools
- 2.3 Unsolved problems and open questions: technology from cell biology, optics, and behavior
- 2.4 Unsolved problems and open questions: genomics and biophysics
- 2.5 Conclusion
- References
- 3 Challenges and opportunities for optochemical genetics
- 3.1 Introduction
- 3.2 Photosensitizing receptors
- 3.3 PCL and PTL development and applications
- 3.4 Advantages and disadvantages of PCLs and PTLs
- 3.5 Conclusion
- References
- 4 Optogenetic imaging of neural circuit dynamics using voltage-sensitive fluorescent proteins: potential, challenges and perspectives
- 4.1 Introduction
- 4.2 The biological problem
- 4.3 The large scale challenge of circuit neurosciences
- 4.4 The current approach to the large-scale integration problem
- 4.5 Large-scale recordings of neuronal activities using optogenetic approaches
- 4.6 Genetically encoded voltage indicators: state of development and application
- 4.7 Unsolved methodological / technical challenges
- References
- 5 Why optogenetic "control" is not (yet) control
- Acknowledgments
- References
- 6 Optogenetic actuation, inhibition, modulation and readout for neuronal networks generating behavior in the nematode Caenorhabditis elegans
- 6.1 Introduction - the nematode as a genetic model in systems neurosciencesystems neuroscience
- 6.2 Imaging of neural activity in the nematode
- 6.2.1 Genetically encoded Ca2+ indicators (GECIs)
- 6.2.2 Imaging populations of neurons in immobilized animals
- 6.2.3 Imaging neural activity in freely moving animals
- 6.2.4 Other genetically encoded indicators of neuronal function
- 6.3 Optogenetic tools established in the nematode
- 6.3.1 Channelrhodopsin (ChR2) and ChR variants with different functional properties for photodepolarization
- 6.3.2 Halorhodopsin and light-triggered proton pumps for photohyperpolarization
- 6.3.3 Photoactivated Adenylyl Cyclase (PAC) for phototriggered cAMPdependent effects that facilitate neuronal transmission
- 6.3.4 Other optogenetic approaches
- 6.3.5 Stimulation of single neurons by optogenetics in freely behaving C. elegans
- 6.4 Examples for optogenetic applications in C. elegans
- 6.4.1 Optical control of synaptic transmission at the neuromuscular junction and between neurons
- 6.4.2 Optical control of neural network activity in the generation of behavior
- 6.5 Future challenges
- 6.5.1 Closed-loop optogenetic control and optical feedback from behavior and individual neurons
- 6.5.2 Requirements for integrated optogenetics in the nematode
- References
- 7 Putting genetics into optogenetics: knocking out proteins with light
- 7.1 Introduction
- 7.2 Protein degradation
- 7.3 Light stimulation
- References
- 8 Optogenetic approaches in behavioral neuroscience
- 8.1 Introduction
- 8.2 Approaches to dissect neuronal circuits: determining physiological correlations, requirement and sufficiency of neurons
- 8.3 Optogenetic analysis of simple stimulus-response-connections
- 8.4 Optogenetic and thermogenetic analysis of modulatory neurons: artificial mimicry of relevance
- 8.5 Conclusion
- References
- 9 Combining genetic targeting and optical stimulation for circuit dissection in the zebrafish nervous system
- 9.1 Introduction
- 9.2 Zebrafish neuroscience: Genetics + Optics + Behavior
- 9.3 Genetic targeting of optogenetic proteins to specific neurons
- 9.4 Optical stimulation in behaving zebrafish
- 9.5 Annotating behavioral functions of genetically-identified neurons by optogenetics
- 9.5.1 Spinal cord neurons (Rohon-Beard and Kolmer-Agduhr cells)
- 9.5.2 Hindbrain motor command neurons
- 9.5.3 Tangential neurons in the vestibular system
- 9.5.4 Size filtering neurons in the tectum
- 9.5.5 Whole-brain calcium imaging of motor adaptation at single-cell resolution
- 9.6 Future directions
- References
- 10 Optogenetic analysis of mammalian neural circuits
- 10.1 Introduction
- 10.2 Optogenetic approaches to probe integrative properties at the cellular level
- 10.2.1 Excitatory signal integration at dendrites
- 10.2.2 Control of excitatory signal integration by inhibition or neuromodulation
- 10.2.3 Long-term analysis of synaptic function
- 10.3 Circuits and systems level
- 10.4 Optogenetics and behavior: testing causal relationships in freely moving animals
- References
- 11 Optogenetics to benefit human health: opportunities and challenges
- 11.1 Introduction
- 11.2 Opportunities for translational applications
- 11.3 Safety challenges
- 11.4 Need for feedback
- 11.5 Conclusion
- References
- 12 Optogenetic tools for controlling neural activity: molecules and hardware
- 12.1 Overview
- 12.2 Molecular tools for sensitizing neural functions to light
- 12.3 Hardware for delivery of light into intact brain circuits
- References
- 13 In vivo application of optogenetics in rodents
- 13.1 Introduction
- 13.2 Sleep / wake regulation
- 13.3 Addiction
- 13.4 Fear, anxiety and depression
- 13.5 Autism and schizophrenia
- 13.6 Aggression
- 13.7 Breathing
- 13.8 Seizures
- 13.9 Conclusion
- Acknowledgments
- References
- 14 Potential of optogenetics in deep brain stimulation
- 14.1 DBS history and indications
- 14.2 Electrical DBS: advantages and drawbacks
- 14.3 Potential of optogenetic stimulation
- 14.4 Conclusion
- References
- 15 Optogenetic approaches for vision restoration
- 15.1 Introduction
- 15.2 Proof-of-concept studies
- 15.3 Light sensors
- 15.4 rAAV-mediated retinal gene delivery
- 15.5 Retinal cell-type specific targeting
- 15.6 Summary
- References
- Further reading
- 16 Restoration of vision - the various approaches
- 16.1 Introduction
- 16.2 The various conditions to be treated
- 16.3 State of the various restorative approaches
- 16.3.1 Neuroprotection
- 16.3.1.1 Encapsulated cell technology (ECT)
- 16.3.1.2 Electrostimulation
- 16.3.1.3 Visual Cycle modulators
- 16.3.1.4 Gene replacement therapy
- 16.3.1.5 Stem cell approaches
- 16.3.1.6 Optogenetic approaches
- 16.3.1.7 Electronic retinal prosthesis
- 16.3.2 Cortical prosthesis
- 16.3.3 Tongue stimulators
- 16.4 The current situation
- 16.5 Open Questions
- 16.6 Conclusion
- References
- Selected registered clinical trials as by February 2013
- 17 Optogenetic approaches to cochlear prosthetics for hearing restoration
- 17.1 Background and state of the art
- 17.2 Current research on cochlear optogenetics
- 17.2.1 Current and future work on cochlear optogenetics aims at
- 17.3 Potential and risks of cochlear optogenetics for auditory prosthetics
- References
- 18 History in the making: the ethics of optogenetics
- References
- 19 Optogenetics as a new therapeutic tool in medicine? A view from the principles of biomedical ethics
- 19.1 Principles of optogenetics
- 19.2 Principles of biomedical ethics
- 19.2.1 Respect for the patient's autonomy
- 19.2.2 Nonmaleficence
- 19.2.3 Beneficence
- 19.2.4 Justice
- 19.3 Conclusion
- References
- Appendix : Dahlem-Conference (Berlin, September 2-5, 2012): "Optogenetics. Challenges and Perspectives."
- Index
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