PITTSBURGH - Much like snowflakes, no two neurons are exactly
alike. But it's not the size or shape that sets one neuron apart
from another, it's the way it responds to incoming stimuli.
Carnegie Mellon University researchers have discovered that this
diversity is critical to overall brain function and essential in
how neurons process complex stimuli and code information. The
researchers published their findings, the first to examine the
function of neuron diversity, online in Nature
Neuroscience.
"I think neuroscientists have, at an intuitive level, recognized
the variability between neurons, but we swept it under the rug
because we didn't consider that diversity could be a feature.
Rather, we looked at it as a fundamental reflection of the
imprecision of biology," said Nathan N. Urban, professor and head
of CMU's Department of Biological Sciences. "We wanted to
reconsider that notion. Perhaps this diversity is important - maybe
it serves some function."
Estimates say that the human brain alone has upwards of 100
billion neurons, which can be broken down into a number of
different types. While members of the same type look structurally
alike, and, as a group, contribute to completing the same overall
task, each individual neuron in that group fires in response to
subtle differences in the incoming stimulus. Typically
neuroscientists average out this heterogeneity to obtain their
results, assuming that the variability is a "bug of biology."
"When we think about computer chips, variability in hardware
clearly can be very destructive. Manufacturers spend a lot of time
and expense making sure each processor on a chip is identical,"
Urban said. "The brain is considered to be one of the most
sophisticated computers there is. We were intrigued by the idea
that the brain might make use of the messy, complex nature of its
biological hardware to function more efficiently."
Urban and postdoctoral student Krishnan Padmanabhan, both
researchers in CMU's Department of Biological Sciences and the
joint CMU/University of Pittsburgh Center for the Neural Basis of
Cognition, tested single neurons' responses to a complex stimulus.
By placing an electrical probe into individual excitatory neurons
called mitral cells and exposing them to a complex
computer-controlled noise stimulus, the researchers were able to
determine how each cell responded. They found that out of the
dozens of neurons they tested, no two had the exact same response.
While the researchers believed that these results were striking on
their own, it led them to wonder whether or not the neurons were
giving a messy version of a single response, or if they were each
providing different pieces of information about the stimulus.
To test their hypothesis, the CMU researchers used a tool called
spike-triggered averaging that allowed them to determine what
feature of the stimulus causes each neuron to respond. They found
that some responded to rapid changes in the stimulus and others to
slower changes; still other neurons responded when the input signal
changed in a regular or rhythmic way. The researchers then computed
the information contained in the outputs of highly diverse sets of
neurons and compared it to that of groups of more similar neurons.
They found that the heterogeneous groups of neurons transmitted two
times as much information about the stimulus than the homogeneous
group.
"Diversity is an intrinsic good," Urban said. "A population in
which each member is a little different in terms of what they can
do is a more efficient and more effective population. It's like a
baseball team - if you want to win, you shouldn't put nine pitchers
on the field."
Aside from its role in information coding, the researchers
believe neuronal diversity also could play a role in neurological
disorders like epilepsy, Parkinson's disease and schizophrenia. In
these conditions, there is a disruption in the synchrony and
rhythmicity of neuronal firing. In the case of epilepsy and
Parkinson's, groups of neurons fire simultaneously, causing
seizures or tremors. In schizophrenia, some neurons have a reduced
ability to coordinate firing in certain situations, such as during
attention tasks. Changes in the diversity of neuronal populations
may alter the ease with which neurons enter into these rhythmic
firing patterns.
Additionally, the researchers want to discover how diversity is
achieved. Neurons of a given type are typically born at the same
stage of development, with many of them coming from the same
progenitor cell. Urban hopes to discover how neurons diversify
during development, what proteins are involved and if any type of
training or exposure enhances diversity.
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