February 23, 2005

Brain Circuitry More Precise Than Suspected

Salk News

Brain Circuitry More Precise Than Suspected

La Jolla, CA – A hallmark of brain organization is that nerve cells (neurons) with similar function are grouped together. But Salk Institute for Biological Studies research published in Nature on February 24 shows that neighboring neurons also keep secrets that they share only with trusted friends.

A team led by Salk scientist Ed Callaway demonstrated that neurons in the cortex of the brain only ‘talk’ directly to a few of their close neighbors and these connected neighbors get their information from the same sources. This organization separates neurons into precisely interwoven sub-networks, like neighborhood cliques.

“This might not make for the friendliest neighborhood, but it probably makes the brain smarter,” said Callaway. “Precise sub-networks of neurons allow more sophisticated computations than are possible in a fully connected network.”

Callaway’s research builds upon previous studies of the brain’s architecture including the Nobel-Prize winning laboratory work by Torsten Wiesel and David Hubel in the 1960s. They showed that brain cells with similar functions are organized into vertical slices called ‘functional columns.’ Although this organization seems biologically efficient, neuroscientists have remained puzzled about the need for so many neurons located in the same area of the brain, to carry out the same function.

“We have shown that the thousands of neurons in these columns are not the same,” said Callaway. “There are fine-scale connections within the columns so that different neurons right next to each other could be involved in very different functions because they’re connected differently and don’t even talk to each other directly.”

Callaway and his colleagues Yumiko Yoshimura from Nagoya University in Japan and Jami Dantzker, now at Stanford University, developed new experimental and analystical methods to show that fine-scale, ‘functional networks’ of neurons are embedded within the classical, large-scale functional column. They used glass microelectrodes to record from neurons in fine slices of rodent brain tissue. By listening in on two neighboring neurons, both at the same time, they could determine whether both neurons were receiving the same messages from other neurons.

“Most of the time the two neurons were not connected to each other and were listening to different neurons in the neighborhood,” explains Callaway. “But when they were connected to each other they were hearing the same messages.”

That the brain’s circuitry is organized on a much finer scale than previously suspected creates new challenges for future studies.

“Right now, people are placing electrodes in the brain and recording from 100 neurons simultaneously and it turns out this is relatively uniformative,” said Callaway. “That’s probably because most of them aren’t connected or even communicating with each other.”

The new findings highlight the need for methods that can distinguish between neurons in separate sub-networks. Callaway and colleagues are developing new techniques to allow gene expression to reveal chains of interconnected neurons.

The new directions suggested by Callaway’s research could help answer basic questions about brain disorders such as schizophrenia or depression. “It’s necessary to understand how the circuitry works normally if you’re ever going to figure out what goes wrong with it,” said Callaway.

The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine, which was proven safe and effective in 1955, has eradicated almost all cases of the crippling disease poliomyelitis, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.

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