Map My Brain

With every smell, memory, or flicker of emotion, tangled pathways of electrical activity light up in our brains and process the information, creating a concise impression of a world photoshopped by our neurons.

But these neuronal pathways don’t line up in a simple, linear transfer of information — there are trillions of synapses, and only recently have researchers really begun to dive into the extensive connections.

Each circuit is an intricate wiring of neurons that transmits signals through an electrical patchwork. Ultimately, every human function comes down to these “wiring diagrams” — maps of specific neuron connections that promote proper brain function.

Neuroscience is starting to move away from more traditional studies, like that of neuron structure or general functions in areas of the brain, and is shifting toward tracking connectivity. Scientists are trying to fill in the middle ground, to untangle the brain’s highly complex neural circuitry, and ultimately lay it out in a decipherable map.

Researchers are tweaking their techniques, incorporating elements of bioengineering and computational optics to expand the realm in which they can study the neuron and its connections in the brain. Some researchers have adapted Nobel-prize winning super resolution microscopy to scrutinize tiny details of neurons that were previously undistinguishable. Scientists hope that eventually these techniques can compile a new foundation for understanding cognition and mental health.

“Figuring out how the neurons come together to make these circuits is a big, rapidly advancing area of neuroscience today,” says Joshua Sanes, Harvard professor and researcher at Harvard’s Center for Brain Science. “Our motivations come from the fact that [neurons] underlay all brain activities, and that there are some psychiatric diseases that are suspected to occur through mis-wirings in the brain.”

In 2007, Sanes helped neuroscience reach a colorful breakthrough. Jeff W. Lichtman, Harvard professor of neuroscience and researcher at Harvard’s Center for Brain Science, and Sane’s research teams developed a technique known as Brainbow, a part of the Center’s Connectome Project.

Meant to tease apart the long tracks of neurons in the brain, the Brainbow method individually labels neurons with fluorescent proteins. These proteins express up to 100 different colors at a time, bringing colorful order to what was once an indiscriminate glob of neurons.

Sanes compares it to the wirings of a computer. All of the wires need to be accounted for and correctly connected, especially the ones involved in complicated circuits. Neurons are a lot like that, there are long “wires” that come from the bodies of neurons called axons and dendrites, and they hook up with other neurons to make precise patterns of connectivity. But if the wires aren’t correctly connected, the neural message gets distorted and can lead to mental deterioration.

“Having the wires in different colors lets you trace them and see where they go,” says Sanes. Currently, he and other scientists are building off of this colorful map to develop other research techniques that help chart connections in the brain.

Outside of the Connectome Project, other researchers at Harvard like Adam Cohen, professor of chemical biology and physics, and Venkatesh Murthy, professor of molecular and cellular biology, are using stimulation techniques to activate neurons and study their response in real time. Cohen has engineered a technique in which the neuron itself is able to make a protein that lights up to indicate electrical activity, and this light can then propagate through circuits of up to 100 neurons.

“The particular trick that Adam Cohen’s lab did is a phenomenally rational and beautiful design,” says Murthy. “It’s one of the best forms of this type of indicator.”

The light-up protein is called “Optopatch” and when engineered to a neuron, can be stimulated by a particular kind of light. This light activates the electrical impulse, and researchers can watch as Optopatch’s red glow fluoresces outwards, highlighting the signal’s path.

Murthy hopes to use this light-up pathway to help track neurons and even map the neural counterparts of particular smells.

While Murthy and Sanes aim to decipher larger neural circuits in the brain, researchers like Jan Tonnesson, at the University of Bordeaux, are taking a more detailed approach, zooming in on intricacies of the neuron that, until recently, have never been seen before. Tonnesson and his colleagues have applied the Nobel-prize winning microscopy technique called STED, more commonly known as super resolution microscopy, to study tiny details of the neuron — specifically, miniscule spines that extend from one neuron to the next, making the synapses that create the connections Sanes and Murthy are interested in studying.

“It opens up a completely new world for us,” says Tonnesson.

Super resolution microscopy allows researchers to clearly see images up to four times smaller than other microscopy techniques, and Tonnesson is taking advantage of that, exploring the microcosms of single neurons.

He and his colleagues at the University of Bordeaux stimulate each spine as if by another neuron and use the super resolution to gather data on how each spine responds individually to the contact. A single neuron may have thousands of spines, and while each spine is independently contacted, the total stimulation is what elicits a signal down the neuron, potentially propagating a circuit.

Tonnesson recognizes that, while super resolution is new to neuroscience, it offers a new angle in analyzing neurons and how neuronal structures may affect proper signal sending.

“We should treat a lot of this as on-going, moment-to-moment innovation,” says Murthy. “None of this is the final product, and I think part of the excitement is simply that we’re seeing what is possible. Sure, there are specific things that we are discovering now, but they’re opening doors to many more things in the upcoming decades.”