Optogenetics - The Dark Side of the Light (Optics and genetic engineering to measure and manipulate cells)

Grapelander

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In salt ponds it is noticed that different bacteria are sensitive to specific light frequency that caused their activation.:
In particular, synechococcus, halobacteria, and dunaliella affect the color of salt ponds.

salt.JPG
This leads to the discovery of Opsins.

How Does Optogenetics Work?
Optogenetics began with the discovery of opsins, such as ChR2. Opsins are light-sensitive channels that cause the depolarization or hyperpolarization of neurons through mechanisms such as the influx of ions or protein signaling cascades (Kim et al. 2017).

Opsins are sensitive to specific wavelengths of light, leading to the activation or inhibition of neural activity. For example, blue light (~470 nm) activates ChR2, causing an influx of Na+ ions and, in turn, depolarizing the neuron (Boyden et al. 2005). With viral expression and transgenic animal models, researchers can target optogenetic probes to genetically-defined neuron populations and across brain-wide projections (Kim et al. 2017).

Multi-disciplinary collaborations between neuroscientists, biologists, and engineers have led to the expansion of the optogenetic toolbox. Opsins have been discovered for manipulating neurons on or off at varying speeds and with different wavelengths of light (see Table 1). For example, Halorhdopsin, an inhibitory opsin, was found to turn off neurons, and red-activated opsins, such as JAWS, were developed to penetrate deeper into the brain (Kim et al. 2017).

In neuroscience, optogenetics has enabled scientists to link neural circuits, behaviour, and function (Kim et al. 2017).


Optogenetics Guide
Optogenetics tools can be broadly classified based on their functions into two groups:
  • Actuators are genetically-encoded tools for light-activated control of proteins; e.g., microbial opsins and optical switches
  • Sensors are genetically-encoded reporters of molecular signals; e.g., calcium indicators
Opsins are light-gated ion channels or pumps that absorb light at specific wavelengths. Upon activation by light, these channels and pumps respond by opening or closing, which conducts the flow of ions into or out of the cell. Scientists have identified a variety of naturally occurring microbial opsins that respond to different wavelengths of light, like blue or yellow light. These various opsins also initiate different electrochemical responses, such as nonspecific cation influx vs. proton efflux. Researchers have used genetic engineering to improve these natural opsins - by inducing point mutations to alter the absorption spectrum or adding trafficking signals to localize opsins to the cell membrane.

Optogenetics with SOUL
Investigator Guoping Feng and colleagues have developed optogenetic tools that allow non-invasive stimulation of neurons in the deep brain.
In order to stimulate neurons with minimal invasiveness, Feng and colleagues engineered a new type of opsin. The original breakthrough optogenetics protocol used channelrhodopsin, a light-sensitive channel discovered in algae. This new study creates a method that can activate any mouse brain region, independent of its location, non-invasively.


video: Amygdala Mouse


article w/video: Optogenetics: Light as method for brain cell remote control

article: Optogenetics
Optogenetics is a technique that involves the use of light to manipulate the activity of cells with high temporal and spatial precision, either in vitro or in vivo. By allowing individual cell types to be selectively targeted, and their activity switched on and off over a biologically relevant timescale of milliseconds, optogenetics provides a degree of specificity and control far greater than that which can be achieved using drugs or lesions. In 2010, Nature declared optogenetics to be their ‘method of the year’, while Science classed it as one of the breakthroughs of the last decade.

article: Optogenetics: A New Technology To Control The Human Brain. Will People Prevent the Rise of A “New Totality”?
Doctor Sarah Lisanby from the National Institute of Mental Health in Maryland can use those brain maps to make different parts of the human body move by the magnetic stimulation of its brain even against his own will (see this). To do this, she is using a magnetic coil which pulsates a magnetic field in a specific frequency, corresponding to the frequency of the activity of neurons in the brain spot, which controls the movements of a specific body part. The magnetic field can produce electric currents in the neurons, responsible for those movements, across the skull.
The brain research financed by the USA and the European Union produced a discovery of the new technology of the control of the activity of the human brain. It is called optogenetics and it is using light. To make this work, it is necessary to introduce special proteins into neurons in the brain by means of special viruses.

Then the light, blinking in the brain in a specific frequency will produce the same neuronal activity as normal neuronal activity in the brain would produce.
 
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Grapelander

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article w/video:
Optogenetics: The Planned Path to Complete Control of Our Brains? “Manipulation of Memories, Emotions and Thoughts”
Efforts are in full swing worldwide to install wireless interfaces in the human brain: so-called communication tools, between brain and computer. One of the fastest emerging methods for this is optogenetics. There are now more than 1,000 laboratories worldwide, including those of government organizations, working on various optogenetic methods.

Optogenetics requires only LED light that irradiates neurons in the brain. The irradiation takes place, for example, through the brain cover or through nano-LEDs implanted in the body.

According to this, the WEF sees optogenetics as one of the most important technologies. On their homepage, we find this quote:
“Our brains are made up of billions of cells called neurons, and these neurons communicate with each other through neural circuits. Optogenetics allows us, for the first time ever, to manipulate the messages these neurons send to each other. The technique could potentially be used to manipulate memories, emotions and thoughts…”

With senior politicians from the European Commission, such as Ursula von der Leyen, on friendly terms with the WEF, it is no surprise that the European Commission is also raving about optogenetics:
“Although we may not realize it, neurons are central to our ability to understand and interact with our environment. Thanks to optogenetics, these cells can now be controlled by light with high precision.”

It was also the EU Commission that introduced the controversial ban on incandescent light-bulbs in 2009, making seamless LED use possible in the first place.
 
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Grapelander

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from Spartacus substack:
Optogenetics and Magnetogenetics
One approach to experimental stimulation of nervous systems is to genetically sensitize nervous tissue to light and electromagnetic fields. Optogenetics is a technique that has been used in tissue cultures and mouse experiments in laboratory settings for over a decade. The method is deceptively simple; transgenic animal tissue is given genes that code for light-sensitive proteins, and then fiber optics pipe laser light into this tissue to stimulate a response.

Nature – Laser used to control mouse’s brain — and speed up milkshake consumption
Neuroscientists at Stanford University in California conducted their experiments on mice that were genetically engineered to have light-sensitive neurons in a brain region called the orbitofrontal cortex. That area is involved in perceiving, and reacting to, rewards. By shining a laser at specific neurons, the researchers increased the pace at which the mice consumed a high-calorie milkshake. The results, reported on 12 November at the annual meeting of the Society for Neuroscience in San Diego, California, illustrate for the first time that the technique, known as optogenetics, can control behaviour by activating a sequence of individual cells.
Other techniques include the so-called “Magneto” protein, which attaches ferritin to membrane-bound ionic gateways to allow them to be stimulated with electromagnetic fields.

Genetically engineered ‘Magneto’ protein remotely controls brain and behaviour
The new technique builds on this earlier work, and is based on a protein called TRPV4, which is sensitive to both temperature and stretching forces. These stimuli open its central pore, allowing electrical current to flow through the cell membrane; this evokes nervous impulses that travel into the spinal cord and then up to the brain.
Güler and his colleagues reasoned that magnetic torque (or rotating) forces might activate TRPV4 by tugging open its central pore, and so they used genetic engineering to fuse the protein to the paramagnetic region of ferritin, together with short DNA sequences that signal cells to transport proteins to the nerve cell membrane and insert them into it.
Nature – Genetically targeted magnetic control of the nervous system
Optogenetic and chemogenetic actuators are critical for deconstructing the neural correlates of behavior. However, these tools have several limitations, including invasive modes of stimulation or slow on/off kinetics. We have overcome these disadvantages by synthesizing a single-component, magnetically sensitive actuator, “Magneto,” comprising the cation channel TRPV4 fused to the paramagnetic protein ferritin. We validated noninvasive magnetic control over neuronal activity by demonstrating remote stimulation of cells using in vitro calcium imaging assays, electrophysiological recordings in brain slices, in vivo electrophysiological recordings in the brains of freely moving mice, and behavioral outputs in zebrafish and mice. As proof of concept, we used Magneto to delineate a causal role of striatal dopamine receptor 1 neurons in mediating reward behavior in mice. Together our results present Magneto as an actuator capable of remotely controlling circuits associated with complex animal behaviors.
However, this approach has met with setbacks:

Two Studies Fail to Replicate Magnetogenetics Research
Several recent studies in high-profile journals reported to have genetically engineered neurons to become responsive to magnetic fields. In doing so, the authors could remotely control the activity of particular neurons in the brain, and even animal behavior—promising huge advances in neuroscientific research and speculation for applications even in medicine. “We envision a new age of magnetogenetics is coming,” one 2015 study read.
But now, two independent teams of scientists bring those results into question. In studies recently posted as preprints to bioRxiv, the researchers couldn’t replicate those earlier findings.
Nevertheless, techniques such as these may be used as a component in brain-computer interfaces, however, they require genetic engineering, which can be very inefficient in adult organisms.

Gene therapy is like changing the blueprints to a house that’s already been built. If you’re reading this, you’re an organism of fairly advanced maturity, yourself. Your genes have been expressed continuously since your birth, and your tissues are representative of those genes.

Neurons in the CNS have very, very low turnover in adults. Even with advances in things like CRISPR/Cas9 and gene delivery and transfection into the cells of living organisms using nanotech and viral vectors, genetic engineering of humans to make nervous tissue fully receptive to external stimuli would likely require germline edits or in-utero gene therapy, before the tissues have differentiated into clusters of specialized cells.

For everyone else, it would be necessary to find methods to stimulate nervous tissue as it already exists.
 
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Synchron Has Started Human Testing For Its New Brain Implant
Synchron was started in Australia, but the Australian laws on what you can put inside a human brain are more strict than in America so they moved to the US for their further experiments. Recently FDA approved the Synchron practices and got a go-ahead signal for their Stent-electrode recording array (Stentrode). A guy named Graham Felstad is the first of the 6 people that will have the Stentrode implant done, this project is funded by the National Institute of Health and it cost 10 million dollars. This will allow the patients to text, call, and do pretty much anything a normal person can do with their internet devices just by thinking about it.

Synchron Announces First Human U.S. Brain-Computer Interface Implant
Synchron, an endovascular Brain-Computer Interface (BCI) company, today announced the first human BCI implant in the United States. This procedure represents a significant technological milestone for scalable BCI devices and is the first to occur in the U.S. using an endovascular BCI approach, which does not require invasive open-brain surgery.
The Stentrode is implanted within the motor cortex of the brain via the jugular vein in a minimally-invasive endovascular procedure. Once implanted, it detects and wirelessly transmits motor intent using a proprietary digital language to allow severely paralyzed patients to control personal devices with hands-free point-and-click.


400 Miles of Blood Vessels in the Brain
Synchron has developed an endovascular brain computer interface that can access every corner of the brain using its natural highways, the blood vessels. Our breakthrough platform launches a new frontier for the treatment of neurological diseases: Neurointerventional Electrophysiology (Neuro EP). Our technology will transform three medical verticals: Neuroprosthetics, Neuromodulation, and Neurodiagnostics.

Synchron Has Installed Two Human "Patients" With Direct Brain To Computer Interface
 
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