Follow the brainbow! Fluorescent proteins and neural circuitry

Liz Halvorsen
25 November 2013

Above: Mouse neurons labeled with fluorescent tags (Stephen J. Smith)

Did you know? There are approximately 86 billion neurons in the human brain.

Have you ever wondered how your brain lets you to learn, feel, and perform complex motor tasks like playing an instrument or driving a car? Revolutionary new technologies are allowing researchers to visualize the connections between individual neurons in your brain. By mapping activity and connections between neurons, scientists are beginning to understand what is happening inside the brain and how it is responsible for the tasks you perform on a daily basis.

Neurons are the fundamental building blocks of the brain. Neurons are connected to one another by cellular structures called axons and dendrites. These neural connections form circuits that transmit electrical and chemical impulses, allowing neurons to enhance signals that control movements and sensations, as well as conscious and subconscious thoughts.

Did you know? The distribution of neurons in the brain is not uniform. Most neurons are concentrated in the cerebellum, a small structure at the base of the brain that controls balance, co-ordination, and muscle tone.In recent years, there have been significant advances in the ability to visualize the activity of neural circuits that link brain function to behaviour, thanks to an American initiative called BRAIN (Brain Research through Advancing Innovative Neurotechnologies). This project aims to map the activity of every neuron in the brain, which will greatly improve our understanding of neural diseases and conditions such as epilepsy, Alzheimer’s disease, and autism. It will also reveal the genetic, cellular, and psychological aspects of brain function.

Fluorescent proteins and the “Brainbow” transgene system are key technologies used for imaging complex neuronal circuits. Fluorescent proteins allow neuroscientists to create colourful and detailed images of brain circuitry by producing neurons that fluoresce, or glow, with a variety of colours.

Parts of a neuron. Click image to enlarge (Liz Halvorsen)

Scientists at Harvard University developed the Brainbow by using a Cre/lox DNA recombination system in the neurons of mice. Cre is an enzyme that binds to short segments of DNA known as lox sequences, and randomly removes these segments [6]. This system uses red, blue, and yellow fluorescent proteins attached to a lox DNA sequence to cause each neuron to fluoresce a different colour, depending on which fluorescent genes the Cre enzyme removes.

Did you know? STORM stands for stochastic optical reconstruction microscopy. It's a technique that allows researchers to view neurons at a nanoscopic scale (1-100 billionths of a metre).The Brainbow system produces an extremely complex palette, illuminating the brain with upwards of 100 different colour combinations. The end result is a veritable kaleidoscope that reveals the composition of the brain’s circuitry.

Researchers believe that the Brainbow will eventually provide a comprehensive blueprint of neural connections in the human brain. It may even help reveal the basis of mental illnesses like autism, while increasing knowledge of normal brain function.

Granted, a map of your neural circuitry offers limited information on which connections are most important for health and disease. However, it can be combined with other technologies such as high-speed light sheet microscopy, which allows scientists to observe the activity of individual neurons, to provide a more complete picture of how your brain works. Indeed, these different technologies will be of great value to initiatives like BRAIN that seek to understand how the cellular basis of our neural circuitry gives rise to conscious thoughts and behaviours, as well as its relationship to mental diseases.

References

An activity map of the whole zebrafish brain (Mo Costandi, The Guardian UK) Are There Really as Many Neurons in the Human Brain as Stars in the Milky Way? (Bradley Voytek, Scitable/Nature Education) BRAIN Initiative (The White House) BRAIN Initiative Challenges Researchers to Unlock Mysteries of Human Mind (Francis Collins and Arati Prabhakar, White House Blog) Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative (National Institutes of Health) Centre for Brain Science (Harvard University) Map of the human brain (CBC News) Neuroscience: Making Connections (Jonah Lehrer, Nature) Obama Hopes Mapping Project Reveals Brain’s Mysteries (Simone Pathe, PBS NewsHour) The Life and Death of a Neuron (National Institute of Neurological Disorders and Stroke)

Liz Halvorsen

I recently graduated from the Microbiology Program at UBC. I'm currently a graduate student at BC Cancer Agency researching breast cancer. My research focuses on the role of tumour-infiltrating T cells in breast cancer progression. I am very passionate about cancer research, immunology, and science in general! When I'm not in the lab, I love to play guitar, read popular science, go for a run along the sea wall, or spend time with my dog Bella.


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