CSH researcher Partha Mitra studies the human brain

CSH researcher Partha Mitra studies the human brain

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The physicist turned biologist working to map the entire brain’s circuitry

Partha Mitra sees a landscape dotted with isolated settlements. The researchers in each region focus on their area, but few have taken a step back to tackle the total terrain. A professor in neuroscience and theoretical biology at Cold Spring Harbor Labs, Mitra’s landscape is the brain. The Calcutta-born scientist wants to change that by mapping the entire brain circuitry.

“Parts of the brain get neglected,” he asserted. “I want to get coverage of the whole brain.”

There is considerable scientific research into the regions of the brain responsible for vision and smell, for example, but the core circuitry where emotions reside — apart from the “fear” and “reward” circuitry, has received considerably less attention.
Looking at the interaction of the entire mouse brain should provide a database that researchers exploring a wide range of topics — from evolution to psychiatric disorders — may employ.

Up until the last decade, a significant problem has been the cost of looking at the whole brain. In 1990, the expense for examining a mouse brain at a resolution of one micron was in the millions of dollars. Just for a sense of scale, a human hair is about 100 microns thick. Now, scientists can gather and store that information, which uses as much as 1 terabyte, or 1,000 gigabytes of computer storage, for closer to hundreds of dollars.

Mitra has taken what he calls a meso-level approach to the brain.

“We’re using classical neuroanalytical methods,” Mitra offered. “We inject a tracer into a part of the brain and let neurons transport that, either from synapse to cell body or from cell bodies to synapses.”

The big picture map of the brain is similar to what genetic scientists did when they mapped the human genome. By recognizing how the genome comes together, researchers can look for changes to understand diseases.

A more complete overview of the brain’s circuits could also help provide evidence in evolutionary debates.

“There are big controversies” relating to the brains of different animals, Mitra explained. “There is no empirical evidence to settle the controversy.”

Scientists used to believe brains evolved like onions – with a reptilian core, a “bird brain” intermediate shell and a mammalian cortical outer layer. While this theory has been discredited and scientists have suggested there are portions of the bird brain that are similar to the cortex, the controversy continues.

“Having the circuit diagram for the mouse brain and a comparative diagram for the bird brain of an appropriate species will help settle this,” he explained.

Mitra believes the publication process could use modification and improvement. Within minutes of something major happening in Egypt, people around the world can learn about it. A major advance in a scientific lab, however, can sometimes take years before people see it.

To that end, Mitra releases data as it comes off his experimental pipeline before publishing a manuscript on the subject. While this model is more common in physics, it hasn’t gained the same kind of traction in the biology community.

“The style now accepted in the physics community seems to be a better solution as it speeds up the communication of results,” he suggested.

Mitra believes an author-driven, freely published preprint, followed by a more traditional journal publication, strikes a balance between the conventional publication model and the potential for sharing results in real time.

When he’s not at the lab or at home in Manhattan, Mitra enjoys the chance to practice yoga. He attends three to six classes a week. A certified instructor, he hasn’t taught yoga since last fall.

He has been at Cold Spring Harbor since 2003. He earned a PhD in physics from Harvard and then went to Bell Labs, where he registered for about 10 patents, including improving wireless transmission capacity and holographic data storage.
Mitra also did research for about a decade examining song learning in the Zebra Finch. He believes nature plays a more important role in learning songs than had previously been thought.

The physicist turned biologist — who has also recorded a CD of himself singing Indian music — acknowledged he doesn’t fit into the usual mold of a biomedical researcher.

“I keep a broad scope,” he concluded.