HOW HAS OPTOGENETIC’S INVESTIGATION DEVELOPED THROUGH THE YEARS?

The “far-fetched” possibility of using light for selectively controlling precise neural activity patterns within subtypes of cells in the brain was articulated by Francis Crick in his Kuffler Lectures at the University of California in San Diego in 1999.

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An early use of light to activate neurons was carried out by Richard Fork who demonstrated laser activation of neurons within intact tissue, although not in a genetically-targeted manner.

The earliest genetically targeted method, which used light to control genetically-sensitised neurons, was reported in January 2002 by Boris Zemelman and Gero Miesenböck, who employed Drosophila rhodopsin photoreceptors for controlling neural activity in cultured mammalian neurons.

In 2003 Zemelman and Miesenböck developed a second method for light-dependent activation of neurons in which three ionotropic channels were gated by caged ligands in response to light.

Beginning in 2004, the Kramer and Isacoff groups developed organic photoswitches or “reversibly caged” compounds in collaboration with the Trauner group that could interact with genetically introduced ion channels.

However, these earlier approaches were not applied outside the original laboratories, likely because of technical challenges in delivering the multiple component parts required.

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In April 2005, Susana Lima and Miesenböck reported the first use of genetically-targeted photostimulation to control the behaviour of an animal. They showed that photostimulation of genetically circumscribed groups of neurons, elicited characteristic behavioural changes in fruit flies.

In August 2005, Karl Deisseroth’s laboratory in the Bioengineering Department at Stanford published the first demonstration of a single-component optogenetic system, beginning in cultured mammalian neurons. Using ChR-1, a single-component light-activated cation channel, from unicellular algae, whose molecular identity and principal properties rendering it useful for optogenetic studies, had been first reported in November 2003, by Georg Nagel.

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The groups of Gottschalk and Nagel were the first to extend the usability of ChR-2, for controlling neuronal activity to the intact animal by showing that motor patterns in the roundworm Caenorhabditis elegans could be evoked by targeted expression and stimulation of ChR-2 in selected neural circuits.

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Now optogenetics has been routinely combined with brain region-and cell type-specific genetic methods developed for Neuroscience by Joe Z. Tsien back in 1990s to activate or inhibit specific brain regions and cell-types in vivo.

The primary tools for optogenetic recordings have been genetically encoded calcium indicators (GECIs).

The first GECI to be used to image activity in an animal was cameleon (a photoactivatable engineered variant of Green Fluorescent Protein (GFP) used to study calcium levels in cells), designed by Atsushi Miyawaki, Roger Tsien and coworkers. Cameleon was first used successfully by Rex Kerr, William Schafer and coworkers to record from neurons and muscle cells of the nematode C. elegans. Cameleon was subsequently used to record neural activity in flies and zebrafish.

In mammals, the first GECI to be used in vivo was GCaMP (a genetically encoded calcium indicator), first developed by Nakai and coworkers. GCaMP has undergone numerous improvements, and GCaMP6 in particular has become widely used throughout neuroscience.

In 2010 Karl Deisseroth at Stanford University was awarded the inaugural HFSP Nakasone Award “for his pioneering work on the development of optogenetic methods for studying the function of neuronal networks underlying behavior”.

In 2012 Gero Miesenböck was awarded the InBev-Baillet Latour International Health Prize for “pioneering optogenetic approaches to manipulate neuronal activity and to control animal behaviour.”

In 2013 Ernst Bamberg, Ed Boyden, Karl Deisseroth, Peter Hegemann, Gero Miesenböck and Georg Nagel were awarded The Brain Prize for “their invention and refinement of optogenetics.”

Public Knowledge in Spain

THE CONTROVERSIAL ISSUE:

Should we be able to retrieve lost memories?

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Our group went to Seville’s streets, in Spain, with the aim of getting to know how much did people know about optogenetics and what did they think about the issue. This were the results:

 

 

 

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As the graph show, more than a half of the people (58%) knew what a gene was, but only 15% knew what biotechnology was about. This might be due to the fact that the concept of gene is taught in schools in the subject of biology and it was known what its function was since 1977. For the contrary, biotechnology is a modern discipline hich is currently giving rise to multiple investigation projects and innovative techniques all around the world.

 

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On a scale from 1 to 5, the graph above represents people’s opinions.

Moreover, half of the respondents would let science get back their lost memories, as they would love to remember their youth and the experiences they had when they were kids. However, the other half won’t accept this technique as they don’t see themselves prepared to cope with the negative memories.

 

You Can Do It Too

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The great part about the advancement and exploration of optogenetics is that it is not exclusive to scientists! http://web.stanford.edu/group/dlab/optogenetics/ This link gives a detailed explanation of how you can recreate the experiment at home or school. It also provides information about the materials needed and a way to request that they be sent to you. Over 147 labs across the globe are currently in possession of these materials and furthering the exploration! So what are you waiting for?!

Facts about the Researchers

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Xu Liu 

Born in Shanghai (international connection woohoo!) Liu moved to the US and received his Ph.D from Baylor College of Medicine, Houston, Texas. Liu was able to create “smart flies” during his time at Baylor by changing the expression of a certain gene in the fly brain. He used the fly model for research about learning and memory. He was also able to use light in order to obtain live imaging of how memories form. This exploration with light and memory led to his co-development of the use of optogenetics in manipulating memory at MIT. Xu Liu is lauded as a notable young neuroscientist and commended for his fearlessness. It was Xu Liu’s hope that his discoveries could lay the ground work for the development of treatments for memory related diseases such as PTSD or Alzheimer’s. Unfortunately Xu Liu passed away almost a year ago on February 18th at the age of 37, and left the scientific community with the opportunity to pick up where he left off.

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Steve Ramirez 

Ramirez is a student at MIT pursuing a Ph.D in neuroscience in the Brain and Cognitive Sciences department. The research done with Xu Liu is the first notable contribution Ramirez has made to the scientific community, but one that attracted a lot of media attention. This is because the experiment was able to accomplish Ramirez’s goal to pluck “questions from the tree of science fiction [and] ground them in experimental reality.” He hopes to become a professor and help curious students explores similar interests.

Optogenetics

What is it?

Imagine yourself on a rollercoaster. You feel exhilarated, lively, and so terrified that you might pee in your pants. Now imagine scientists implanting the DNA of a light-sensitive protein, channelrhosopsin,  into specific neurons that can make you feel the same way by zapping them with flashes of light to turn them on or off. This process is called optogenetics. As crazy as it seems, this technique has proven to work. Even though it has not been tested on the human brain, scientist Steve Ramirez and Xu Liu were able to turn on specific neurons that triggered the memory of shock in mice.

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Optogenetics Tested

In 2012, Ramirez and Liu put optogenetics to the test by using mice. It is known that when mice sense danger, they stay as still as possible and make little to no movement. This reaction is called freezing. Using this information, Ramirez and Liu put a mouse in a box and shocked it. When it was shocked, the neurons associated to that shock memory was recalled and they were able to implant channelrhodopsin into those specific neurons. Once this was done, the mouse is put into a completely different box. Since this box is not associated with the shock it had experienced in the first box, the mouse did not freeze and explored the box. Ramirez and Liu then zapped the neurons implanted with channelrhodopsin to bring back the memory of being shocked and the mouse froze. It stayed in one spot and barely moved even though it was not shocked. Through this, an artificial memory of shock was created by turning on the same neurons that were active when the mouse was actually shocked.

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How and Why We Chose to Investigate Optogenetics

We chose to explore this topic because of our interest in how people function. Knowing at least 3 of us have taken IB Psychology, it’s safe to say zapping people, like Milgram did, was far from boring to us. Along with this, we all wondered about how retrieving memory, other than how our brain normally does it, would work. We wanted to find out how people felt about this topic, so we simply asked. With their permission, we interviewed several people asking of their knowledge of and opinions on optogenetics. Some of the responses are what would be expected, while others caught our eyes in a new way haha.

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