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 David Schoppik,
PhD, who conducted the study while a doctoral candidate in the
laboratory of senior author Stephen 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 Howard Hughes 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 behaviorshas 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."
The other co-author of the study was
Katherine Nagel, PhD, at the time a doctoral candidate in the
laboratory of Allison 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 Howard Hughes Medical Institute and by a Conte Center for Neuroscience Research grant.
UCSF
is a leading university dedicated to defining health worldwide through
advanced biomedical research, graduate level education in the life
sciences and health professions, and excellence in patient care.
The University of California, San Francisco. April 2008.
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