A snapshot taken with a confocal microscope of the whole brain of a roundworm. Credit: Toyoshima et al 2024
Joint research
led by Yu Toyoshima and Yuichi Iino of the University of Tokyo has demonstrated
individual differences in, and successfully extracted commonalities from, the
whole-brain activity of roundworms. The researchers also found that computer
simulations based on the whole-brain activity of roundworms more accurately
reflect real-brain activity when they include so-called "noise," or
probabilistic elements. The findings were published in the journal PLOS Computational Biology.
The roundworm Caenorhabditis elegans is a favorite among neuroscientists because
its 302 neurons are completely mapped. This gives a fantastic opportunity to
reveal their neural mechanism at a systems level. Thus far, scientists have
been making progress in revealing the different states and patterns of each
neuron and the assemblies they form. However, how these states and patterns are
generated has been a less explored frontier.
First, the team of scientists measured the neural
activity of each cell that makes up a primitive brain in the roundworms' head
area. To achieve this, the worms were placed in a microfluidic chip, a tiny device designed for worms to be able to "wiggle"
backward and forward while keeping them within the field of view of the
objective lens. Then, using a confocal microscope, the scientists filmed how the neurons reacted to changes in salt
concentrations.
A video taken with a confocal microscope of the
whole brain of a roundworm. Credit: Toyoshima et al 2024
"Although we were able to extract neural 'motifs' common among
individuals," Iino says, "we were surprised to find large individual differences in neural activity. Information
from sensory neurons is
transmitted to 'command' neurons through multiple paths to control behavior.
"Since the neural circuits of C. elegans are thought to be relatively
well conserved among individuals, we had assumed that there would be little
variation in these paths among individuals. But remarkably, we found the
opposite."
The data derived from these "films" of roundworm brains were then
used to create computer simulations of
roundworm brains. However, the first simulations that contained only
deterministic elements generated decaying "neural" activity. By
adding "noise" to the models, the team achieved an accurate
representation of the roundworms' whole-brain activity.
The scientists were not only able to estimate the strength of connectivity
between neurons but also demonstrated that "noise" is essential to
brain activity. This mathematical model could
even potentially be applied to analyze neuronal activity in cases where
complete connectome data is not yet available.
With such possibilities, the number of exciting, new questions seems infinite. But a scientist must choose.
Neural activity motifs (the common elements of brain
activity among individual roundworms) and whole-brain simulation based on
whole-brain activity. Credit: Toyoshima et al 2024
"We
originally designed this study to investigate the neural mechanisms involved
when roundworms are attracted to salt," Iino explains.
"However, to measure whole-brain activity, we needed to keep the roundworms in a narrow channel so that they would not move away. We would like to improve the microscope so that we can track freely moving roundworms and analyze whole-brain activity while they are being attracted to salt."
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