optogenetics Concepts

Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing

by Kevin Davies · 5 Oct 2020 · 741pp · 164,057 words

had treated many patients with schizophrenia and depression, but was frustrated at how poorly we understand those diseases. He was developing a new technique called optogenetics for studying neuronal activity and neurological diseases. Deisseroth’s brainstorm was to introduce a light-sensitive protein called an opsin into a rodent neuron, affording

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tiny fiber optic cable. When he flicked on the light switch, the mouse suddenly started spinning in circles; switched off, the mouse stopped moving.4 Optogenetics was ready for the big time: a tool to study brain function far more precisely than sticking electrodes into the brain or taking blurry MRI

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helped lay the foundation for President Barack Obama’s $300-million BRAIN Initiative. Deisseroth credited Zhang’s skills as “absolutely essential to the creation of optogenetics.”6 Not too many PhD students get to see their handiwork featured in the Times or win a share of a major scientific prize. It

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, 298, 301–320, 356 Genetics advances in, xv–xvi bacterial genetics, 40 biochemical genetics, 131–132 epigenetics, 109, 322 molecular genetics, 18, 58–59, 109 optogenetics, 78–79 prenatal genetics, 155, 355 Genome editing applications, 65–68 artificial intelligence and, 349–350 beginnings of, 19–21, 179–180 benefits of, xvi

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, 216 Oliver, John, 29 Olson, Eric, 175–176 One Child, 268 One in a Billion, 279 O’Neill, Helen, 360 Oppenheimer, J. Robert, 253–254 Optogenetics, 78–79 Oregon Health & Science University, 172, 223 Organ transplants, 6, 163, 281–283 Orkin, Stuart, 157 Ornithine transcarbamylase (OTC) deficiency, 141–144 Ornithopter, xviii

The Future of the Brain: Essays by the World's Leading Neuroscientists

by Gary Marcus and Jeremy Freeman · 1 Nov 2014 · 336pp · 93,672 words

it to “understanding a television program by looking at a single pixel.” As we write this, it is clear that neuroscience is undergoing a revolution. Optogenetics, introduced in 2005, makes it possible to engineer neurons that literally light up when active, switching them on and off with a laser; multielectrode recordings

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, these proteins inside the cell become brighter. In this way, light microscopes can measure neural activity at the cellular level. In addition, using so-called optogenetic tools, they can perturb neural activity by exciting or silencing individual neurons with different colors of light. In zebrafish larvae this can be done in

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make a prediction of what it would do when a set of neurons suddenly falls still? These types of hypotheses need to be tested, and optogenetic tools such as channelrhodopsin and halorhodopsin, capable of exciting and silencing neurons when hit by different colors of light, allow for this and have already

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example, EEG, MEG, fMRI). Similarly, powerful stimulation technologies have been used to causally perturb neural activity and observe the consequences (for example, electrical microstimulation, TMS, optogenetics). While many seminal discoveries, insights, and Nobel Prizes have resulted from these measurement (and stimulation) technologies, a renewed appreciation for the complexity of the overall

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): 609–18. Diester, I., M. T. Kaufman, M. Mogri, R. Pashaie, W. Goo, O. Yizhar, C. Ramakrishnan, K. Deisseroth, and K. V. Shenoy. 2011. “An Optogenetic Toolbox Designed for Primates.” Nature Neuroscience (14): 387–97. Gilja, V., P. Nuyujukian, C. A. Chestek, J. P. Cunningham, B. M. Yu, J. M. Fan

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, at selected developmental time points. Their expression can be silenced at one point of life, then reactivated at another. Advances in techniques of electrophysiology and optogenetics allow researchers to directly target the functions of particular sets of neurons in a highly controlled manner in the living mouse and to make connections

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. Some theorists have held that the measurement problem may be solved by new technology, a subject to which we now turn. Transgenic Mice and the Optogenetic Switch Global broadcasting involves not only feed-forward flow of activation but heavy feedback from frontal to sensory areas. Christof Koch and Nao Tsuchiya (2014

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light, for example, by being infected with genetically altered viruses. In these mice, top-down feedback from frontal to sensory areas can be turned off optogenetically by light sources on the skull or optical fibers implanted in the brain. If there is no top-down attentional feedback there can be no

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distractors but not when there are distractors. How we are supposed to know whether the mice whose top-down feedback has been deactivated by the optogenetic switch are doing their tasks consciously? Koch and Tsuchiya propose to use postdecision wagering in which the mice express their confidence in their choice by

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to betting to get more food pellets. And Koch and Tsuchiya say that one may be able to use postdecision wagering to test whether the optogenetic mice are consciously seeing the stimulus. High confidence would suggest conscious perception; low confidence unconscious perception. But won’t the shutting off of top-down

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may be mediated by different top-down processes from those involved in attention and global broadcasting and so may not be turned off by the optogenetic switch. One way to think about this proposal is to try to imagine what it would be like to be an

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optogenetic mouse. Suppose you are a transgenic being whose optogenetic switch has been flipped so as to preclude top-down attention. And suppose Koch and Tsuchiya are right that you would have

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be to lower one’s confidence in any one percept. Now suppose instead that the prediction of Koch and Tsuchiya is wrong—that when the optogenetic switch is flipped, it knocks out conscious perception as well as top-down attention. Without top-down signals there can be no global broadcasting. Still

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it is hard to predict how confident a perceiver with only unconscious vision would be. In sum, betting might not correlate with consciousness once the optogenetic switch was flipped. The upshot is that although the use of transgenic mice could make an important contribution, it would just be another line of

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. However, even focal electrical stimulation still lacks precision because neural processes the electrical impulse affects are locally entangled nearly everywhere in the brain. By contrast, optogenetic methods provide unprecedented selectivity to turn cells on or off so that the role of selected networks in behavior can be directly tested

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. Optogenetics promises greater selectivity for manipulating each element of a circuit, but will surely have its own pitfalls. Thus, electrical and optically based neurotechnology are poised

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sophisticated electronics, could lead to something approaching what we take for granted as normal vision or hearing. A more far-reaching but potential application of optogenetics is to recreate light sensitivity in remaining retinal cells in order to replace missing photoreceptors altogether. Improvements in the spatial and temporal stimulation patterns informed

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. Few other approaches are sufficiently localized (high spatial resolution) and fast enough (high temporal resolution) to be able to capture action potentials single neurons produce. Optogenetic methods are an exciting alternative, but they have not yet been modified successfully for widespread clinical use as they nominally involve genetic manipulation of the

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provided a wealth of information about collective behaviors of groups of neurons. Numerous efforts are focusing on intra- and extracellular electrophysiological recording stimulation, optical recording, optogenetic stimulation, optoelectrical, and electroacoustic methods to perturb and record the individual activity of neurons in large (and, hopefully scalable) ensembles. All recording technologies embody some

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cell types, whose axons make up the optic nerve, could be reliably predicted, in response to arbitrary visual stimuli. That understanding (in combination with advanced optogenetics and implantable ocular electronics) led to effective treatments for macular degeneration, diabetic retinopathy, and retinitis pigmentosa. Similar techniques helped crack the codes used in the

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diseases such as Alzheimer’s or Parkinson’s cause; by the mid 2050s, almost all medicine, and all neuroscience, had moved to nanobotic platforms; even optogenetics, the workhorse of the early twenty-first century, eventually was displaced. Because of their high spatial specificity—guided by an externally imposed 3-D radio

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body. Microarray. An array containing thousands of small DNA or RNA sequence probes that can perform genetic tests by applying an independent tissue using imaging. Optogenetics. A technique for using light to control neurons. See channelrhodopsins and halorhodopsins. Positron emission tomography (PET). A medical imaging technique that detects gamma rays emitted

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, 162, 269; measurement problem, 161–64, 170–72; nonconceptual representations, 170–72; percepts and concepts, 171–72; precursors to conscious state, 163; transgenic mice and optogenetic switch, 168–70 contrastive method: conscious and unconscious perception, 163; consciousness, 163 copy number variants (CNVs), 236 cortex: grid cell generation, 74; grid cells and

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, 230, 231f MGI, 9 mice: cortex of, 26–27; DNA bar coding of cells, 56–57; MindScope, 28; mutations of genome, 154; transgenic mice and optogenetic switch, 168–70; two-proton imaging of cortex, 107; understanding brain of, 264, 265 microcircuits: brain, 36, 113, 118, 119m 240 microelectrode, 69, 91, 220

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for Research, 124 On the Fabric of the Human Body (Vesalius), 3, 4f Open Connectome Project, 13–14 optical microscope, 256 optical recordings: neurotechnology, 225 optogenetics, xii, 20, 23–24, 79, 154, 226, 227, 266, 273: advanced, 264; methods, 244–45, 260; transgenic mice and, switch, 168–70 orientation selectivity: discovery

Whiplash: How to Survive Our Faster Future

by Joi Ito and Jeff Howe · 6 Dec 2016 · 254pp · 76,064 words

neuroscientists were simply spectators at brain events, watching vast swaths of neurons react to this or that stimulus, and attempting to infer causality. But with “optogenetics,” as Deisseroth and another colleague called the new technique, researchers could stimulate individual neural circuits and observe how they behaved. Boyden is quick to share

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credit for optogenetics—with his collaborators, but also with other scientists who were hot on the trail in 2005 when he and Deisseroth first went public with their

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” required employing molecular biology, genetic engineering, surgery, fiber optics, and lasers.12 Just one of these would find its way onto the standard neurology curriculum. Optogenetics has revolutionized the study of the brain, and since the original discovery Boyden and other researchers have refined the technique so that neurons can be

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mice, and much more easily than their untreated blind cousins. The effect lasted for the full ten months of the study.14 The promise of optogenetics is not limited to neurology, or to the treatment of certain forms of blindness.15 In the decade since Boyden, Deisseroth, and Feng Zhang developed

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and work differently in mammalian cells, allowing multichannel control over mixed groups of cells, or the use of, say, red light instead of blue. Additionally, optogenetics research is helping to stimulate further development of complementary tools, such as neural recording and imaging technologies.19 “There are more than a billion people

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disorder,” says Boyden. “A great many of those diseases—from Parkinson’s to epilepsy to PTSD—might eventually be treated using insights that arose from optogenetics.” Not long after Joi first joined the Media Lab, he orchestrated a trip to Detroit. He had recently launched a program called the Innovator’s

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/article/computers-vs-brains/. 7 Elwyn Brooks White, Here Is New York (New York Review of Books, 1949), 19. 8 Edward Boyden, “A History of Optogenetics: The Development of Tools for Controlling Brain Circuits with Light,” F1000 Biology Reports 3 (May 3, 2011), doi:10.3410/B3-11. 9 Boyden, “A

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History of Optogenetics.” 10 “Edward Boyden Wins 2016 Breakthrough Prize in Life Sciences,” MIT News, November 9, 2015, http://news.mit.edu/2015/edward-boyden-2016-breakthrough-prize

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: Inside the New Science of Neuroengineering,” WIRED, March 2, 2009, http://www.wired.com/2009/03/neuroengineering1/. 13 Katherine Bourzac, “In First Human Test of Optogenetics, Doctors Aim to Restore Sight to the Blind,” MIT Technology Review, February 19, 2016, https://www.technologyreview.com/s/600696/in-first-human-test-of

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-optogenetics-doctors-aim-to-restore-sight-to-the-blind/. 14 Anne Trafton, “Seeing the Light,” MIT News, April 20, 2011, http://news.mit.edu/2011/blindness-

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with Light [Extended Version],” Scientific American, October 20, 2010, http://www.scientificamerican.com/article/optogenetics-controlling/. 16 Ibid. 17 Ernst Bamberg, “Optogenetics,” Max-Planck-Gesellschaft, 2010, https://www.mpg.de/18011/Optogenetics. 18 Udi Nussinovitch and Lior Gepstein, “Optogenetics for in Vivo Cardiac Pacing and Resynchronization Therapies,” Nature Biotechnology 33, no. 7 (July 2015

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): 750–54, doi:10.1038/nbt.3268. 19 Deisseroth, “Optogenetics: Controlling the Brain with Light [Extended Version].” 20 “1985 | Timeline of Computer History,” Computer History Museum, accessed June 7, 2016, http://www.computerhistory.org/timeline/

I, Warbot: The Dawn of Artificially Intelligent Conflict

by Kenneth Payne · 16 Jun 2021 · 339pp · 92,785 words

the full network state of the originating brain in the target. But perhaps something cruder is possible. In a recent experiment, scientists ‘input’ emotion using ‘optogenetics’, a relatively new technique. They were able to stimulate an aggressive response in mice, via genetically modified, light sensitive neurons in its amygdala, an evolutionary

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and rage systems.33 Essentially, they made the mouse furious and aggressive at the flick of a light switch. More recently still, another startling experiment optogenetically stimulated oxytocin neurons in mice via a wireless headset, this time stimulating pro-social behaviours.34 Emotion at the flick of a light switch. Impressive

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. 7333 (2011): 221–226. 34. Anpilov, Sergey, Yair Shemesh, Noa Eren, Hala Harony-Nicolas, Asaf Benjamin, Julien Dine, Vinícius E. M. Oliveira et al. ‘Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors’, Neuron, in press, (2020). 35. See Mitchell, Kevin

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, no. 5 (2017): 117–142. Anpilov, Sergey, Yair Shemesh, Noa Eren, Hala Harony-Nicolas, Asaf Benjamin, Julien Dine, Vinícius E. M. Oliveira et al. ‘Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors’, Neuron, in press, (2020). Ashby, Ross, and Paul

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, Barack object recognition Observe Orient Decide and Act (OODA) offence-defence balance Office for Naval Research Olympic Games On War (Clausewitz), see Clausewitz, Carl OpenAI optogenetics Orca submarines Ottoman Empire (1299–1922) pain Pakistan Palantir Palmer, Arnold Pandemonium Panoramic Research Papert, Seymour Parkinson’s disease Patriot missile interceptors pattern recognition Pearl

Physics of the Future: How Science Will Shape Human Destiny and Our Daily Lives by the Year 2100

by Michio Kaku · 15 Mar 2011 · 523pp · 148,929 words

brain, but they are incapable of tracing the specific neural pathways of thought, perhaps involving only a few thousand neurons. But a new field called optogenetics combines optics and genetics to unravel specific neural pathways in animals. By analogy, this can be compared to trying to create a road map. The

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results of the MRI scans would be akin to determining the large interstate highways and the large flow of traffic on them. But optogenetics might be able to actually determine individual roads and pathways. In principle, it even allows scientists the possibility of controlling animal behavior by stimulating these

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of insects with the push of a button, the reality is much more modest. The fruit fly has roughly 150,000 neurons in the brain. Optogenetics allows scientists to light up certain neurons in the brains of fruit flies that correspond to certain behaviors. For example, when two specific neurons are

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is that scientists are, for the first time in history, tracing the specific neural pathways of the brain that control specific behaviors. MODELING THE BRAIN Optogenetics is a first, modest step. The next step is to actually model the entire brain, using the latest in technology. There are at least two

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Obama, Barack, 5.1, 6.1, 6.2, 6.3, 6.4 Ohmae, Kenichi Oil OLEDs (organic light-emitting diodes) O’Neill, Gerard Optical computers Optogenetics Organ replacement, 3.1, 3.2 Orion Project Orwell, George Ottoman Empire Ozone depletion Pääbo, Svante PAMELA (Payload for Antimatter Matter Exploration and

Behave: The Biology of Humans at Our Best and Worst

by Robert M. Sapolsky · 1 May 2017 · 1,261pp · 294,715 words

Memory,” Nat Rev Nsci 5 (2004): 844; S. Wolff et al., “Amygdala Interneuron Subtypes Control Fear Learning Through Disinhibition,” Nat 509 (2014): 453; R. LaLumiere, “Optogenetic Dissection of Amygdala Functioning,” Front Behav Nsci 8 (2014): 1. 21. T. Amano et al., “Synaptic Correlates of Fear Extinction in the Amygdala,” Nat Nsci

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al., “Preferential Responses in Amygdala and Insula During Presentation of Facial Contempt and Disgust,” Eur J Nsci 24, (2006): 2355. 29. X. Liu et al., “Optogenetic Stimulation of a Hippocampal Engram Activates Fear Memory Recall,” Nat 484 (2012): 381; T. Seidenbecher et al., “Amygdalar and Hippocampal Theta Rhythm Synchronization During Fear

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and the Role of the Locus Coeruleus-Norepinephrine System in Optimal Performance,” J Comp Neurol 493 (2005): 99; M. Carter et al., “Tuning Arousal with Optogenetic Modulation of Locus Coeruleus Neurons,”Nat Nsci 13 (2010): 1526. 32. D. Blanchard et al., “Lesions of Structures Showing FOS Expression to Cat Presentation: Effects

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(2003): 9185; H. Lee et al., “Scalable Control of Mounting and Attack by Ers1+ Neurons in the Ventromedial Hypothalamus,” Nat 509 (2014): 627; D. Anderson, “Optogenetics, Sex, and Violence in the Brain: Implications for Psychiatry,” BP 71 (2012): 1081. 34. K Blair, “Neuroimaging of Psychopathy and Antisocial Behavior: A Targeted Review

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Activation in the Rat Prefrontal Cortex, Nucleus Accumbens, and Dorsal Striatum,” J Nsci 26 (2006): 8810. 77. T. Danjo et al., “Aversive Behavior Induced by Optogenetic Inactivation of Ventral Tegmental Area Dopamine Neurons Is Mediated by Dopamine D2 Receptors in the Nucleus Accumbens,” PNAS 111 (2014): 6455; N. Schwartz et al

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): 77; J. Britt et al., “Synaptic and Behavioral Profile of Multiple Glutamatergic Inputs to the Nucleus Accumbens,” Neuron 76 (2012): 790; G. Stuber et al., “Optogenetic Modulation of Neural Circuits That Underlie Reward Seeking,” BP 71 (2012): 1061; F. Ambroggi et al., “Basolateral Amygdala Neurons Facilitate Reward-Seeking Behavior by Exciting

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,” Sci 340 (2013): 1174; S. Ahmari et al., “Repeated Cortico-Striatal Stimulation Generates Persistent OCD-like Behavior,” Sci 340 (2013): 1234; E. Burguiere et al., “Optogenetic Stimulation of Lateral Orbitofronto-Striatal Pathway Suppresses Compulsive Behaviors,” Sci 340 (2013): 1243. 94. S. Flagel et al., “A Selective Role for Dopamine in Stimulus

Sleepyhead: Narcolepsy, Neuroscience and the Search for a Good Night

by Henry Nicholls · 1 Mar 2018 · 367pp · 102,188 words

getting round it. The party sucks. There’s lots of research that confirms this rocket-like role for hypocretins. Easily the strongest evidence comes from optogenetics, an incredibly powerful approach for studying the brain that de Lecea had a hand in pioneering. ‘If you shine a light in the brain nothing

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cell activity, it doesn’t give a reliable way to take over control of the cell, to manipulate its activity at whim. This is where optogenetics comes in. De Lecea sets a video to play. There is a mouse in a cage with a thin fibre-optic cable running into its

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<https://doi.org/10.1523/jneurosci.1887-05.2005>. p. 108 envy the mouse Antoine R. Adamantidis and others, ‘Neural Substrates of Awakening Probed with Optogenetic Control of Hypocretin Neurons’, Nature, 450.7168 (2007), 420–4 <https://doi.org/10.1038/nature06310>. For the video clip of

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optogenetic activation of hypocretin neurons see <https://images.nature.com/full/nature-assets/nature/journal/v450/n7168/extref/nature06310-s2.mov>. p. 108 surge of hypocretins

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Oneiroi 76–7 online CBT see Sleepio online support 269 opiates 192–3 opossums 3–4 optical stimulation of the SCN 21 OptiNose device 261 optogenetics 106–7 O’Regan, David 205, 211–18 orexins (alternative name for hypocretins) 100–1, 271–2 O’Shea, Michael 235 out-of-body experiences

Dopamine Nation: Finding Balance in the Age of Indulgence

by Anna Lembke · 24 Aug 2021

to reverse the scars of addiction. Vincent Pascoli and his colleagues injected rats with cocaine, which demonstrated the expected behavioral changes (frenzied running), then used optogenetics—a biological technique that involves the use of light to control neurons—to reverse the synaptic brain changes caused by cocaine. Maybe someday

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optogenetics will be possible on human brains. The Balance Is Only a Metaphor In real life, pleasure and pain are more complex than the workings of

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al., “Brain Pathways to Recovery from Alcohol Dependence,” Alcohol 49, no. 5 (2015): 435–52. https://doi.org/10.1016/j.alcohol.2015.04.006. optogenetics: Vincent Pascoli, Marc Turiault, and Christian Lüscher, “Reversal of Cocaine-Evoked Synaptic Potentiation Resets Drug-Induced Adaptive Behaviour,” Nature 481 (2012): 71–75, https://doi

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predisposition to, 87 and moderation of drug use, 87–88, 107–9 motivation to pursue recovery, 104 and new synaptic pathways in recovery, 64 and optogenetics, 64 to pain, 160–68, 234 potential for, measured by dopamine, 2, 49 poverty as risk factor for, 105 and relapses, 57 rising rates of

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temporal horizons, 103–4 and tolerance (neuroadaptation), 55 and willingness to help others, 184 See also specific drugs, including heroin opponent-process theory, 52–53 optogenetics, 64 overtraining syndrome, 167 oxycodone, 21 OxyContin, 18, 22, 131 oxytocin, 183–84 pain addiction to, 160–68, 234 capacity to tolerate, 66 chronic, 55

The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

by Walter Isaacson · 9 Mar 2021 · 700pp · 160,604 words

make the workings of the brain and its nerve cells, known as neurons, more visible. Along with another graduate student, they pioneered the field of optogenetics, which uses light to stimulate neurons in the brain. That allowed them to map different circuits in the brain and gain insights about how they

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; Alexander Aravanis, Li-Ping Wang, Feng Zhang… and Karl Deisseroth, “An Optical Neural Interface: In vivo Control of Rodent Motor Cortex with Integrated Fiberoptic and Optogenetic Technology,” Journal of Neural Engineering, Sept. 2007. 4. Feng Zhang, Le Cong, Simona Lodato, Sriram Kosuri, George M. Church, and Paola Arlotta, “Efficient Construction of

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, The, 255 Office of Scientific Research and Development, 89 oil spills, 232 On the Origin of Species (Darwin), 11, 28 open-source software, 163, 256 optogenetics, 167 Orwell, George, 358–59 osmium hexamine, 57 Our Posthuman Future (Fukuyama), 281 Oviedo Convention, 278 Oxford University, 438, 439 P53 gene, 250–51 PAC

The Quantum Thief

by Hannu Rajaniemi · 1 Jan 2010 · 324pp · 91,653 words

Oubliette obsession with privacy, even to help solve their own murder or a gogol piracy case. ‘Perhaps never,’ the Gentleman says. ‘What?’ ‘This was an optogenetic black box upload. Very crude: it must have been agony. It’s an old trick, pre-Collapse. They used to do it with rats. You

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, gazes fixed on something far, far away, but unseeing, as the fireworks fizzle and die above us. Another trick from the gogol pirate handbook: an optogenetic virus that makes brain cells hypersensitive to certain wavelengths of light. It was not hard to customise it not for the purposes of uploads, but

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Resurrection House behind. The wind on Persistent Avenue feels hot after the chill of the underworld, but the sound of human voices is refreshing. The optogenetic attack at the party left him feeling disoriented, with a mild headache. A med-Quiet inspected him along with the rest of the guests, but

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. Work. Create. Live.’ ‘Why are we talking about this now?’ Isidore asks. He closes his eyes. His head is throbbing: a double dose of the optogenetic weapon in less than a day. The tzaddik’s voice sounds hollow and far away. ‘Because of this,’ the tzaddik says. ‘Because you keep getting