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Neurons Pathway in Brain Wired Alike Researchers Show

By Suzanne Trimel

What is depicted is a corticotectal trigger neuron at center. On either side is a grid, upon which are placed all examples (from different animals) of the two major follower classes from the study.

A research team at Columbia University, tracking the pathways between neurons in the visual cortex of the brain, has discovered for the first time that these connections are extremely precise and identical from one individual animal to another.

The findings suggests a genetic basis for these particular circuits of the brain. The research was carried out by a team led by Dr. Rafael Yuste, associate professor in the department of biological sciences, in collaboration with Dr. James Kozloski, at the time a postdoctoral fellow in Yuste's laboratory, and Farid Hamzei-Sichani, an undergraduate at Columbia. Their findings were published in the August 3 issue of Science

New imaging technology developed in Yuste's laboratory allowed the researchers to actually view the pathways by which neurons connect to one another. By stimulating a "trigger" cell to detect which neurons among hundreds were activated, they found to their surprise that these connections, much like stops on a subway system, followed a consistent, precisely organized pattern. When one neuron was stimulated, a second one, always the same, was triggered. Most striking was the realization that this pattern was identical from one animal to the next among 15 laboratory mice they studied. "We were astonished by the similarities in the results from different animals and even found it spooky," said Yuste.

The fact that these neuronal connections are the same from animal to animal suggests that these particular circuits of the brain may be genetically determined.

"It's very hard to imagine how the connections can end up being so similar in different animals that have had different life experiences unless the circuits have been determined from the outset," said Yuste.

Yuste said he was surprised by the identical circuitry among different animals. "Even though these animals are relatively young they still could have been subjected to different environmental and developmental aspects. I was surprised, frankly. I was expecting a much less rigid architecture in the cortical connections."

Examining brain slices using the optical probing technique, Yuste was able to "track" the circuits of the cortex, much like an engineer takes apart a radio and tries to determine which wire connects to another. "We were asking very simple questions about how the 'wires' function," he said. "Are they the same in different animals? Or does each individual animal have different wiring? Can we reproduce the connections between neurons? Or are the connections completely random?"

For nearly a century, scientists have divided over how neurons in the brain's cortex -- the complex area that Yuste and his colleagues studied – connect. In mammals, the cortex is the larger part of the brain. In humans it is the primary site for mental functions like perception, memory, control of voluntary movements, language, imagination, art and music – much of which makes us not only humans, but individuals.

Scientists do not yet understand how the cortex works. One theory suggests that it is a precise machine built with connections that follow a specific pattern while another supports the idea that random or probabilistic connections actually allow animals and humans to mix information that different neurons carry, thus generating novel associations and ideas.

Since the 17th century when English philosopher John Locke conceived of the human mind as a tabula rasa – an empty slate that receives outside impressions after birth – scientists have debated whether or how much the brain is shaped by experience or determined at birth.

In the 1960s in their Nobel Prize-winning research, Torsten Wiesel and David Hubel showed that early visual experience during a critical period can change the connectivity of particular neurons in the visual cortex. "Most scientists now believe that certain features of brain functions involve genetic determination and others experience activity-dependent development – that there is a bit of both," said Yuste. "The challenge is that we don't really know where the dividing line is."

Yuste said it is important for scientists to understand how neurons, the fundamental unit of nervous tissue, make connections in the brain. "The cortex of the brain is solving very complicated computations using particular 'nuts and bolts,' " said Yuste. "Unless we understand how this hardware works – how the neurons connect and what they tell each other -- we will never achieve a real understanding of how the brain functions. The fact that we find extremely specific connections indicates that the cortex is a very precise machine with a specific purpose."

Many neuroscientists, Yuste said, view the cortex as a kind of universal computer and believe figuring out how it functions could lead computer scientists to develop better computers. "It's quite clear that the cortex is solving complicated, and apparently different, computations effortlessly," said Yuste. "It's possible that the reason why the cortex is so powerful has to do with its using a general strategy for computing. If we can understand this natural computation strategy, this might allow us to build better computers."

Over the years, Yuste's laboratory has received funds from the National Eye Institute in an effort to understand how the brain processes visual information at the very basic level. The primary visual cortex is responsible for analyzing motion, color, and visualizing the edges of shapes and is one of the best understood parts of the brain.

Yuste has also received funding from the National Institute of Neurological Diseases and Stroke for mapping pathological pathways that could lead to a cure for epilepsy. Kozloski's postdoctoral fellowship was funded by the National Institute of Mental Health. He is now on the research staff at IBM Watson Research Labs. There is evidence that epilepsy and schizophrenia, as well as visual amblyopias and congenital defects caused by drug addiction, may result from the "miswiring" or "misfiring" of cortical circuits. Yuste's research on the brain's circuitry has implications for screening drugs that could activate or inactivate particular circuits.

Published: Aug 10, 2001
Last modified: Sep 18, 2002

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