brainbow

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Brainbow is the process by which individual neurons in the brain can be distinguished from neighboring neurons using fluorescent proteins. By randomly expressing different ratios of red, green, and blue derivatives of green fluorescent protein in individual neurons, it is possible to flag each neuron with a distinctive color. This process has been a major contribution to the field of connectomics; the study of neural connections in the brain.

Expression of combinations of three different fluorescent proteins in a mouse brain produced ten different colored neurons. Individual neurons in a mouse brain appear in different colors in a fluorescence microscope. This “Brainbow” method enables many distinct cells within a brain circuit to be viewed at one time. 

The “Brainbow” technique is applicable to many cell types, including he muscle fibers of the tongue. Just as in the brain, the fluorescence is generated by the “Brainbow” transgene randomly recombined by the Cre/lox system. Different cell types handle the recombination step differently, leading to a unique mixture of fluorescent proteins and the colorful pattern.

Image: Here the intercrossed muscle fibers in the tongue of a mouse embryo (day 14) are labeled with random combinations of the fluorescent proteins dTomato (red), YFP (green) and Cerulean (blue). This image displays the maximal intensity projection of a confocal image stack (20x 0.8 NA oil objective).

It never seems like there are enough Brainbow images around. This is a relatively new one from this year's Olympus Bioscapes competition in which the cerebral cortex of a mouse has been Brainbow-labelled. This mouse was likely thinking about Christmas lights.

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Photo by Mr. Pierre Mahou, Dr. Emmanuel Beaurepaire, and Dr. Karine Loulier

“Brainbow” zebra fish.

Neurons are labeled in multiple colors with Brainbow fluorescence microscopy. Three fluorescent proteins (cyan, yellow and red) are randomly taken up by various neurons, offering a palette of dozens of colors to help scientists follow complex neural pathways. Shown here is a five-day-old zebra fish larva viewed from the dorsal side, captured using a 20X objective.

Image credit: Dr. Albert Pan, Harvard University, Cambridge, Mass., U.S.

It’s not only the sheer number of neurons in the human brain that’s so mind-boggling but also the way in which these neurons are connected with one another. In fact, it has been said that between the eighty six billion neurons in the human brain there are more possible connections than the number of atoms in the Universe.

As you can imagine, it can be extremely difficult to study a machine as intricate as the human brain. However, we need to remember that in the end of the day we are using the intelligence it has to offer us to learn more about itself. In the past few decades, neuroscientists have come up with ingenious way to shed light upon these vast networks of neurons.

One such successful method was seen with Professor Jeff Lichtman of Harvard University and his team as they developed a breed of genetically engineered mice. These mice had neurons programmed to produce a combination of red, green and yellow fluorescent proteins. This resulted into what they like to call a “brainbow” - where each and every neuron of the mouse has a different shade of color allowing it to be distinctively set apart from the rest. This means that Lichtman and his team can not only effectively map a mouse brain but can also observe when specific neurons fire off each other.

Lichtman’s studies not only allow us to observe patterns in the mouse brain like never before but also creates a new possible method of studying the human brain in the future.

A variation of the “Brainbow” gene adds a transcriptional “roadblock” to inhibit expression of the fluorescent proteins until Cre is activated. By placing Cre under the control of a tissue-specific promoter, the “Brainbow” effect can be activated in one tissue of the mice. This is called the “Confetti” mouse.

Image: Here the “Confetti” gene is transiently activated in all liver cells in a mouse ~4 weeks of age. As a result, each cell independently recombines the “Confetti” gene toward one of four fluorescent proteins. Image was taken after 2 months tracing with a Leica SP5 microscope; 10x objective.

Neurons in a zebrafish embryo

Zebrafish have proven invaluable for understanding what we know about nerves and the brain. Observing brain development and interrogating how growing neurons find their correct targets are possible thanks to the transparent, genetically malleable nature of zebrafish embryos. Recently, scientists have developed a technique called “Brainbow” that individually colors each neuron, allowing researchers to map the start and end points of neural circuits. Applying Brainbow to zebrafish will allow researchers to visualize how neurons connect with one another during development and how different diseases disrupt this process.

Image by Dr. Albert Pan, Harvard University.

I can’t into visual art so have a vague pillar men modern au idea thing

 - Kars works with stem cells (which he affectionately calls “vampires” since they’re immortal and you feed them with blood serum) and helps with obtaining transgenic animals for making brainbows and such. Probably does some very shady research on the side. Never really grew out of his Obnoxious Middle School Dawkins Phase. Is that guy whose laboratory notebooks all have saccharine-cute kittens on the cover along with titles like “Biohazard waste disp. 2017” in bold black marker (written with great caution as to not tread on the kittens). Every intern is deathly afraid of him.

Fun fact: after hours he’s the local vulture culture enthusiast, has a whole lot of cool bones and would really love to get an eagle skeleton but fully understands why that’s still illeagle. Keeps like seven living pets, all incredibly pampered.

 - Esidisi is an expert on military history. He hosts one of those discovery channel shows that’s half interesting info on famous battles, weapons and strategies and half “let’s check what this cannon will do to a bunch of crash dummies” with morbid humor and some truly awful puns sprinkled in. He has tattoos and piercings for miles and is very buff which leads to at least one popular meme (Buff Historian Advice, eg. top text: “when facing a cuirassier”, pic of shirtless Esidisi giving you a thumbs up, bottom text: “suplex the horse”. He loves these. When he has a guest lecture somewhere he always puts one of them in the presentation). He also takes interest in ancient conspiracy theories and mysteries.

Fun fact: while his parents really did name him after the band AC/DC (…why), he likes to joke it’s actually a.C./d.C. as in antes de Cristo / después de Cristo (before/after Christ) and how do you not become a historian with this name?


They meet in a way that’s probably less “meet cute” and more “meet bloody - but don’t worry the blood’s not mine haha”, and then everything goes really fast and suddenly they’re married with two adopted kids and when did that happen?? Time sure flies