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You just move like a mouse, or do so abnormally like a mutant mouse

PLOS

The brain is no longer a mysterious black box. Elucidation of the human genome is having a profound impact on the understanding of brain function in health and disease. However, genes cannot be systematically manipulated in humans, and this is why animal models of human functions are being developed.

Now that the human and mice genome sequences are known, unprecedented opportunities arise for the advancement of psychology and psychiatry. But there are some fundamental limitations: while much of psychology and psychiatry relies on the evaluation of questionnaires and self-reports, mice are notoriously non-compliant with these.

Therefore, the only alternative is to resort to objective tests. Indeed mice models of behaviour have been proposed, yet such models are generally considered to be a seriously inadequate representation of human-specific disorders.

A new holistic approach to assess model behaviour has been proposed and evaluated by researchers at the University of Tokyo (Yoshiharu Yamamoto, Toru Nakamura and Zbigniew Struzik) and Osaka Bioscience Institute (Toru Takumi). The lifestyle of the mouse has been monitored in a way comparable with that of monitoring humans. Every move of the animal is recorded by pressure sensors under the cage, and this information is collected for more than 24 hours. The findings are published in the journal PLoS ONE.

This information is next processed to reflect how many small and how many large movements the mouse undertakes and, very importantly, how long they last. These durations of small and large movements are then processed to provide a mathematical representation of how probable it is that the mouse will make small or large moves of a certain duration.

Similarly, the team at the University of Tokyo evaluated the lifestyle of healthy humans by monitoring their wrist activity for more than 24 hours and plotting similar graphs of probabilities of large and small moves. The surprising discovery came when the team compared the probabilities of durations between mice and humans and realised that there is no difference in behaviour statistics.

In fact, the observed probabilistic laws expressed as graphs for the durations of both resting periods and active periods collapsed when rescaled by the well-known allometric factor, capturing the difference in average resting and activity durations between mice and humans.

No less stunning was the realisation that mice with an artificially eliminated gene regulating the circadian rhythm ---so-called Period2 gene "knock out" mice--- showed a distortion in the resting duration probabilistic law analogous to that previously observed by the team in humans suffering from major depressive disorder.

This discovery is not only expected to help in the practical diagnosis and evaluation of depressive disorder, but even in the development of a new drug targeting the "depression genome".

The observation that healthy mice show behaviour statistics during rest and activity indistinguishable from humans may have a fundamental impact on the understanding of the higher brain functions. This intriguing hypothesis has been suggested by the team, who point out that similar statistics are shown in activity avalanches between neuronal cells grown in vitro in a Petri dish.

The statistics of such an artificially raised neuronal "society" are also known to change when information exchange is pharmacologically suppressed. The statistics of such neurons unable to contact their neighbours come close to those observed in "depressed" mice and humans ---could the analogy run as deep as this" The current finding indicates that perhaps, yes indeed.

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Citation: Nakamura T, Takumi T, Takano A, Aoyagi N, Yoshiuchi K, et al. (2008) Of Mice and Men -- Universality and Breakdown of Behavioral Organization. PLoS ONE 3(4): e2050. doi:10.1371/journal.pone.0002050

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT (URL live from April 30): http://www.plosone.org/doi/pone.0002050

PRESS-ONLY PREVIEW: http://www.plos.org/press/pone-03-04-yamamoto.pdf

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