Wednesday, August 27, 2014

Why are scientists trying to map every single neuron in the brain?

A computer diagram of neural connections in the mouse brain, part of the most extensive mammal brain map ever. Allen Institute for Brain Science

Researchers around the world are engaged in a massively difficult project to map the entire human brain. And, recently, they have reported a few promising advances.

On April 3, the journal Nature released two major papers on brain mapping. The first described a chart of the connections between brain cells in a mouse — the most detailed mapping yet of any mammal. The other looked at which genes were active in the brains of human fetuses.

Confused about what that might mean? Then let's back up a second here. Below is a very basic primer on why scientists are mapping the human brain, how they go about doing that, and what these latest studies mean.

Wait, why are scientists trying to map the human brain?

The ultimate goal is to chart the locations of the roughly 85 billion neurons in the brain, their roughly 100 trillion connections, and how they all function.

If that sounds like a tall order, it's because it is. The hope is that doing this will lead to a far greater understanding about how brains work and especially how mental disorders come about and could be treated.

Who's doing the mapping?

This isn't one big, organized project. It's a bunch of scientists across the world working on various undertakings.
The only species that's had every single neuron mapped out is a microscopic worm

There's a lot of excitement about brain mapping right now. The US and the EU recently dumped some significant money into the mix. Obama's BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies) funding started in 2014 and should provide $100 million a year for each of 10 years. (For comparison, the National Institutes of Health neuroscience budget is about $5.5 billion a year.) The European Commission has promised $1.3 billion over 10 years to make a detailed computer model of the human brain. The American and European projects will start officially collaborating later in 2014. Many private projects are also underway.

Is it hard to map a human brain?

Yes. The human brain is extremely complex. Different people's brains have cells connected in different ways, so researchers can't just map one brain and call it a day. In addition, contrary to previous scientific thought, everyone's brain develops new cells and new connections throughout life. If you're alive, your brain is changing.

So how do you map a brain?

One way is to start with less complex organisms. The only species that's had every single neuron mapped out is a microscopic worm called C. elegans. This was a lot easier, since the worm has only 302 neurons. (That's 0.0000004 percent the number of neurons in a human brain.)

That's what makes the mouse-mapping paper in Nature so interesting. It describes the Allen Mouse Brain Connectivity Atlas: the most detailed connection map of a mammal's brain. Researchers created it by adding a fluorescent protein to one tiny area of a mouse brain at a time (each area had about 100 to 500 neurons). Then they tracked where the glowing protein flowed. How? Well, they removed the mouse brains afterward and chopped them up into teeny-weeny pieces. Hongkui Zeng, who directed the research, told me in an email that she estimates they mapped 15 to 20 percent of all mouse-brain neurons.

Is a human brain more difficult to map than a mouse brain?

Dti-sagittal-fibers

Tracking water flow to trace neurons. (Thomas Schultz/Wikimedia Commons)

Yes. We can't really put fluorescent proteins inside humans and then take out their brains to see where the glowing went. So, instead, scientists use other techniques including a type of MRI that tracks water flow in brain tissue. It's usually easier and faster (not to mention less expensive) to study thousands of mice than thousands of people, and resolution is always an issue.

So we just need to find the neurons' connections, and we're done?

Not exactly. Researchers compare mapping the brain's connections to mapping a city's roads: you know where the streets are but have no idea what the traffic is like.

So another major area of brain mapping has been documenting where different genes are turned on. This was the point of the other April 3, 2014 Nature study, which tracked the locations of genetic activity in brains from four human fetuses. The researchers looked at tens of thousands of genes during a key time when areas that handle higher-order functions such as reasoning and memory develop.

Another big task is studying which neurons are firing when. The most impressive work on this so far is probably a study published in the spring of 2014. In it, researchers individually turned on each of 1,054 different neuronal circuits in fruit fly larvae and then recorded what behaviors occur for every single one. Please note: fruit fly larvae are simple creatures with only 10,000 neurons and with behaviors far simpler than humans'. (The researchers classified 29 total "general behaviors" in the larvae such as "turn-avoid" or "back up" humans have a few more that that.)

Scientists are currently mapping brain function in humans at a much rougher level, using equipment such as high-resolution fMRI machines. For a great overview of researchers mapping brain function in people, check out this New York Times story.

How long will it take to map a human brain?

A long time. Researchers needed four years to plot the main routes (about 15 to 20 percent) of the roughly 75 million neurons in the mouse brain. By contrast, the human brain has about 85 billion neurons — about 1,100 times as many as a mouse has. Hongkui Zeng, who led the mouse map work, told me in an email that a human brain connection map with a similar resolution as the mouse one "can be done within the next 10 years." But that would still be a small fraction of the entire humans brain.

So, yeah. It's a long haul. But that doesn't mean it's pointless. Here's a piece from Scientific American Mind on why trying but failing is still worth it, an analysis of how terribly complex the task is and why heading toward "less wrongness" in our understanding of the brain is still incredibly useful.

What do we do once we have a brain map?

All kinds of things. Maybe we could make brain-like computers that are as creative as we are. Maybe we could figure out exactly what chemical imbalances are going on in people with mental illnesses and how much serotonin to pump into which parts of the brain to treat them. And maybe we could finally answer questions that are currently in the realm of philosophy —€” what is love? what is beauty? what are dreams?

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