Study breaks ground in revealing how neurons generate movement

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Study breaks ground in revealing how neurons generate movement

http://www.eurekalert.org/pub_releases/2008-04/uoc--sbg042408.php

When the eye tracks a bird's flight across the sky, the visual

experience is normally smooth, without interruption. But underlying

this behavior is a complex coordination of neurons that has remained

mysterious to scientists. Now, UCSF researchers have broken ground in

understanding how the brain generates this tracking motion, a finding

that offers a window, they say, into how neurons orchestrate all of

the body's movements.

The study, reported in the April 24 issue of Neuron, reveals that

individual neurons do not fire independently across the entire

duration of a motor function as traditionally thought. Rather, they

coordinate their activity with other neurons, each firing at a

particular moment in time.

" Scientists have known that neurons that connect to muscles initiate

movement in a coordinated fashion. But they have not known how the

neurons we are studying – which coordinate these front-line neurons --

commit the brain to move the eyes, " says co-lead author

Schoppik, PhD, who conducted the study while a doctoral candidate in

the laboratory of senior author Lisberger, PhD, at the

University of California, San Francisco.

" For decades, scientists have been asking, `Do the signals involve a

handful of neurons or thousands " What is the nature of the commands " '

The classical understanding has been that one class of neuron is

responsible for one movement, such as generating eye movement to the

left, and that it remains active across the entire duration of a

behavior, " he says.

" The new findings suggest a totally different way of looking at how

movement is controlled across time, " says Lisberger, a

Medical Institute Investigator at UCSF, where he is professor of

physiology, director of the W.M. Keck Foundation Center for

Integrative Neuroscience, and co-director of the Sloan Center for

Theoretical Neurobiology.

The findings, the researchers say, could inform efforts to develop

neural prosthetics to treat paralysis and motor dysfunctions, such as

those resulting from stroke. " The brain's messages don't reach the

muscles in these conditions, " says Schoppik, " so it's critical that

the drive to these prosthetics reflect what the brain is trying to do

to move muscles. Understanding how multiple neurons work together

could influence the type of software created to drive these devices. "

The investigation of how neurons give rise to motor behaviors has

been stymied until now, says Schoppik, by the difficulties inherent

in studying more than one neuron in action at a time during the

course of a behavior. In the current study, the scientists overcame

this obstacle in a study of macaque monkeys that had been trained to

track a moving object with their eyes.

Basing their approach on two key pieces of information -- first, that

when a neuron responds to a stimulus there is always a slight

variation in its performance, a phenomenon that neuroscientists

traditionally refer to as " noise, " and, second, that each attempt of

the eye to pursue a moving target is also unique – they proposed that

some aspects of neural variation may reflect behavioral variation.

They used this inherent variability as a probe. Using a formula from

financial securities market analysis that looks at how individual

stocks behave at a given time within the context of fluctuations in

the larger financial market, they explored how individual neurons

would behave relative to their neighbors.

They compared the deviations from the average spiking activity of

single neurons and simultaneous deviations from the mean eye

velocity. They also measured the degree to which variation shared

across two pairs of concurrently active neurons.

The data demonstrated that individual neurons encode different

aspects of behavior, controlling eye velocity fluctuations at

particular moments during the course of eye movement, while the

population of neurons collectively tiles the entire duration of the

movement.

The analysis also revealed the strength of correlations in the eye

movement predictions derived from pairs of simultaneously recorded

neurons, and suggests, the researcher say, either that a small number

of neurons are sufficient to drive the behavior at any given time or

that many neurons operate collectively at each moment.

The finding, says Lisberger, underscores the importance of recording

for more than one neuron at a time. " There is a lot that we can learn

from how multiple neurons interact. "

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The other co-author of the study was Nagel, PhD, at the

time a doctoral candidate in the laboratory of J. Doupe, MD,

PhD, a professor of psychiatry and physiology and a member of the

Keck Center for Integrative Neuroscience at UCSF.

The study was funded by the Medical Institute and by a

Conte Center for Neuroscience Research grant.