Today we are closer than ever to understanding the biological basis of human thought. In a major first for neuroscience, researchers have produced an image showing almost an entire vertebrate brain at work — down to the level of individual neurons. Soon we'll have a human brain "activity map" which reveals how electrical impulses in the brain correlate to thought patterns, biological processes, and more.
The neurons in question belong to a zebrafish embryo, and the researchers come from HHMI's Janelia Farm Research Campus. In the video up top, the activity of individual neurons appear as flashes, detonating across the fish's entire larval brain. And while the brain of a zebrafish only contains about 100,000 neurons (compared to the tens of billions in the human brain), it represents an important step along the path to creating a Brain Activity Map for us apes, a project into which the Obama administration may soon funnel billions of dollars.
According to findings published in the latest issue of Nature Methods, microscopist Phillip Keller and neurobiologist Misha Ahrens have modified an existing imaging technique (called light sheet microscopy) in such a way that enables them to record neuronal activity from the entire volume of the zebrafish's brain. They did this while the embryo was alive, and with a temporal resolution of 0.8 Hz (meaning they were recording activity about once every second). All told, Keller and Ahrens were able to capture "more than 80% of all neurons at single-cell resolution. "
Emphasis added, because that last bit is important. Imaging whole-brain activity isn't really new. Neither is mesauring the activity of single neurons. Doing both simultaneously, however, is really impressive, and hugely valuable from an experimental standpoint – akin to being able to see the individual dots of a pointillist masterpiece and the painting as a whole all at once.
The researchers used their newfound imaging abilities to demonstrate how their novel technique could be used to uncover two functionally defined neuron-circuits across the zebrafish's brain. The video below is a 3D visualization of a circuit of neurons extending from the zebrafish's hindbrain into its spinal cord.
“It’s phenomenal,” says Yuste... “It is a bright star now in the literature, suggesting that it is not crazy to map every neuron in the brain of an animal.” Yuste has been leading the call for a big biology project that would do just that in the human brain, which contains about 85,000 times more neurons than the zebrafish brain.
The resolution offered by the zebrafish study will enable researchers to understand how different regions of the brain work together, says Ahrens. With conventional techniques, imaging even 2,000 neurons at once is difficult, so researchers must pick and choose which to look at, and extrapolate. Now, he says, “you don't need to guess what is happening — you can see it”.
It'll be interesting to see what impact existing brain-mapping projects like this one have on bringing Yuste's proposed project to fruition. Many scientists have complained that such an undertaking lacks the clear conceptual aims of other major, government-funded research endeavors (the Human Genome Project, for example).
Others have voiced concern that a massive Brain Mapping Project would lead to the messy reapportioning of already limited scientific funding. Will studies like this one, which demonstrate the feasibility of whole brain mapping in less complex organisms, lead some of them to reconsider their grievances? Or will its shortcomings (the fact that it really only works in transparent organisms — like zebrafish embryos) keep it from being taken into serious consideration?
Images and video by Keller and Ahrens, via Nature and Discover; Seurat's Sunday on La Grande Jatte via Wikimedia Commons