Optogenetics

Optogenetics......Page 4
List of contributing authors......Page 6
Content......Page 10
Introduction......Page 16
1.1 Photoreceptors......Page 22
1.1.2 Biophysics of photoreceptors and signal transduction......Page 25
1.2 Engineering of photoreceptors......Page 27
1.2.1 Approaches to designing light-regulated biological processes......Page 28
1.3 Case study – transcriptional control in cells by light......Page 32
1.4 Conclusion......Page 33
References......Page 35
2.2 Background: current functionality of tools......Page 38
2.3 Unsolved problems and open questions: technology from cell
biology, optics, and behavior......Page 40
2.4 Unsolved problems and open questions:
genomics and biophysics......Page 43
2.5 Conclusion......Page 46
References......Page 48
3.1 Introduction......Page 50
3.2 Photosensitizing receptors......Page 51
3.3 PCL and PTL development and applications......Page 54
3.4 Advantages and disadvantages of PCLs and PTLs......Page 56
References......Page 57
4.3 The large scale challenge of circuit neurosciences......Page 62
4.4 The current approach to the large-scale integration problem......Page 63
4.6 Genetically encoded voltage indicators: state of development
and application......Page 64
References......Page 67
5 Why optogenetic “control” is not (yet) control......Page 70
References......Page 74
6.1 Introduction – the nematode as a genetic model in systems
neurosciencesystems neuroscience......Page 76
6.2.2 Imaging populations of neurons in immobilized animals......Page 77
6.2.3 Imaging neural activity in freely moving animals......Page 78
6.3.1 Channelrhodopsin (ChR2) and ChR variants with different functional
properties for photodepolarization......Page 79
6.3.3 Photoactivated Adenylyl Cyclase (PAC) for phototriggered cAMP-dependent
effects that facilitate neuronal transmission......Page 80
6.3.5 Stimulation of single neurons by optogenetics in freely behaving C. elegans......Page 81
6.4.1 Optical control of synaptic transmission at the neuromuscular junction and
between neurons......Page 83
6.4.2 Optical control of neural network activity in the generation of behavior......Page 84
6.5.1 Closed-loop optogenetic control and optical feedback from behavior and
individual neurons......Page 85
6.5.2 Requirements for integrated optogenetics in the nematode......Page 87
References......Page 89
7.2 Protein degradation......Page 94
7.3 Light stimulation......Page 100
References......Page 103
8.1 Introduction......Page 106
8.2 Approaches to dissect neuronal circuits: determining
physiological correlations, requirement and sufficiency of
neurons......Page 107
8.3 Optogenetic analysis of simple
stimulus-response-connections......Page 108
8.4 Optogenetic and thermogenetic analysis of modulatory
neurons: artificial mimicry of relevance......Page 110
References......Page 112
9.2 Zebrafish neuroscience: Genetics + Optics + Behavior......Page 116
9.3 Genetic targeting of optogenetic proteins to specific neurons......Page 117
9.5.1 Spinal cord neurons (Rohon–Beard and Kolmer–Agduhr cells)......Page 118
9.5.3 Tangential neurons in the vestibular system......Page 119
9.5.5 Whole-brain calcium imaging of motor adaptation at single-cell resolution......Page 120
References......Page 121
10.1 Introduction......Page 124
10.2.1 Excitatory signal integration at dendrites......Page 125
10.2.2 Control of excitatory signal integration by inhibition or neuromodulation......Page 126
10.2.3 Long-term analysis of synaptic function......Page 128
10.3 Circuits and systems level......Page 129
10.4 Optogenetics and behavior: testing causal relationships in
freely moving animals......Page 135
References......Page 136
11.2 Opportunities for translational applications......Page 142
11.3 Safety challenges......Page 144
References......Page 145
12.2 Molecular tools for sensitizing neural functions to light......Page 148
12.3 Hardware for delivery of light into intact brain circuits......Page 151
References......Page 152
13.2 Sleep / wake regulation......Page 158
13.3 Addiction......Page 160
13.4 Fear, anxiety and depression......Page 163
13.6 Aggression......Page 165
13.8 Seizures......Page 166
References......Page 167
14.2 Electrical DBS: advantages and drawbacks......Page 172
14.3 Potential of optogenetic stimulation......Page 173
References......Page 174
15.1 Introduction......Page 176
15.2 Proof-of-concept studies......Page 177
15.3 Light sensors......Page 179
15.4 rAAV-mediated retinal gene delivery......Page 181
15.5 Retinal cell-type specific targeting......Page 182
References......Page 184
Further reading......Page 186
16.2 The various conditions to be treated......Page 188
16.3.1.1 Encapsulated cell technology (ECT)......Page 189
16.3.1.3 Visual Cycle modulators......Page 190
16.3.1.5 Stem cell approaches......Page 191
16.3.1.7 Electronic retinal prosthesis......Page 192
16.3.3 Tongue stimulators......Page 196
16.5 Open Questions......Page 197
References......Page 198
Selected registered clinical trials as by February 2013......Page 200
17.1 Background and state of the art......Page 202
17.2 Current research on cochlear optogenetics......Page 204
17.3 Potential and risks of cochlear optogenetics for auditory
prosthetics......Page 205
References......Page 206
18 History in the making: the ethics of optogenetics......Page 208
References......Page 214
19.1 Principles of optogenetics......Page 216
19.2 Principles of biomedical ethics......Page 217
19.2.1 Respect for the patient’s autonomy......Page 220
19.2.2 Nonmaleficence......Page 221
19.2.3 Beneficence......Page 222
19.2.4 Justice......Page 223
19.3 Conclusion......Page 224
References......Page 225
Appendix : Dahlem-Conference (Berlin, September 2–5, 2012): “Optogenetics.
Challenges and Perspectives.”......Page 228
Index......Page 238