PRESS RELEASE
November 19, 2010
Keio University
Kyushu University
Brain asymmetry is critical for proper memory function: Evidence from
behavioral experiments with brain asymmetry deficit mice
In the collaboration with the research group of Assoc. Prof. Isao Ito of Kyushu University, the
research group headed by Prof. Shigeru Watanabe of Keio University reported that the
spontaneous mutant mice that have a brain asymmetry deficit (bilateral right-sidedness) showed
spatial memory deficit in two behavioral tasks. The results suggest that bilateral asymmetry of the
brain is critical for proper memory function.
Two tasks were used to test memory performance of the mutant mice. In a maze task in which
mice learn and remember a location of baited food, and this task was testing the long-term
memory capacity. In lever-pressing task, mice remember a lever position of left or right and they
subsequently have to select the lever not pressed earlier, and this task was used for testing the
short-term memory capacity. Comparing with the control mice, whose brain has bilateral
asymmetry, these mutant mice show poorer memory performance. These results suggest that
left-right asymmetry is critical for normal brain functions in regards to both long-term and
short-term memory.
The group of Assoc, Prof. Ito previously discovered that the neural circuitry of the mutant
mouse hippocampus was bilaterally symmetrical (exhibits bilateral right-sidedness), as opposed
to those of the control mice that are bilaterally asymmetrical. The present study further revealed
that such asymmetrical circuitry is critical for proper memory function of the brain. These results
was published on line in October 17, 2010 edition of the science journal, PLoS ONE.
PLoS ONE 5(11): e15468.
（URL: http://www.plosone.org/doi/pone.0015468）.
1. Summary
Mutant mice, that have a brain asymmetry deficit (bilateral right-sidedness), were tested in two
behavioral tasks that examined long-term and short-term spatial memory. In the first task, mice
were released into a circular area to find a baited food location. The position where the mice
released was varied in each trial but the baited location remained the same. Mice learned the
baited location using spatial arrangements of room interior as spatial cues. Compared with control
mice, the mutant mice explored areas where the food was not baited for longer time (Fig. 4).
In the second task, mice were trained to remember the lever position (left or right) in an
experimental apparatus. In each trial, mice were first given a lever to remember. After a delay
interval (the length was varied in every trial), mice were given two alternative levers and they
received food reward when pressing the opposite to the lever given previously. Mutant mice
showed as good position discrimination performance as control mice, but the forgetting rate was
significantly faster in the mutant in comparison to the control (Fig. 5).
These two experiments indicate that the lack of hemispheric asymmetry impaired both longand short-term memory performances in the mutant mice, which in turn suggest that the left-right
asymmetry in the brain circuitry is critical for proper memory function.
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2. Significance and Background
The human body structure appears to be symmetrical between left and right, but internal
organs such as the heart and kidney are arranged asymmetrical between left and right. The brain
structure also appears to be symmetrical but its functions are known to be asymmetry between
the two hemispheres. For example, speech function is well-known to be localized in the left
hemisphere in human brain. However, little is known about why the functions are asymmetrical
between the two hemispheres and how the lack of hemispheric asymmetry influences the
cerebral functions.
The group led by Assoc. Prof. Isao Ito of Kyushu University previously found that normal mice
have left-right asymmetry in the hippocampal circuitry, whereas the iv mouse (inversus viscerm
mutant mouse) lacks this hippocampal asymmetry (Fig. 3). Although morphological and
electrophysiological studies have been conducted, no behavioral experiments have been carried
out so far. The consequence of the brain asymmetry deficit in the mutant mice thus has been
unknown. In the present study, the researchers conducted two types of behavioral experiments
testing the memory capacity in the mutant mice and found that the mutant mice show inferior
memory performance. These results were the first to suggest that the hemispheric asymmetry is
critical for proper memory function of the brain.
3. Future Development and Challenges of the Study
Two types of tasks reported in the present paper concerns spatial memory. A future study
should concern whether the abnormality of the left-right asymmetry also impairs memory in
general or the impairment is restricted to the spatial memory. It remains also unknown whether
the abnormality of the mutant mouse is only hippocampal circuitry. Further examination in
gene-knockout mice would be required to specify more exact evaluation of functional
consequences of the abnormality of brain asymmetry. The present study is an important
breakthrough by demonstrating that the hippocampal asymmetry is a useful model system for
exploring the molecular basis of brain asymmetry,
Complementary explanation: What is the hippocampal asymmetry?
Hippocampal neurons make synapses to transfer signals from one neuron to another.
Synapses are made on the apical and basal dendrites of individual neurons. NMDA receptor
NR2B subunits, molecules known to be important in the formation of new memories, are localized
in these synapses. In normal mice, left and right hippocampal neurons make synapses with
distinct characteristics. Left hippocampal neurons make NR2B dominant synapses on the apical
dendrites and NR2B nondominant synapses on the basal dendrites. On the other hand, right
hippocampal neurons make NR2B nondominant synapses on the apical dendrites and NR2B
dominant synapses on the basal dendrites. Therefore, hippocampal circuitry is asymmetrical
between left and right. Whereas, in the iv mouse hippocampus, the left-right asymmetry is lost
and both left and right hippocampus show the properties of the right (bilateral right-sidedness).
That is, both left and right hippocampal neurons form NR2B dominant synapses on the basal
dendrites and NR2B nondominant synapses on the apical dendrites. In the present study, we
examined the memory capacity of iv mice and found that the mutant mouse shows inferior
memory performance.
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Inquiries:
Ms. Toh, Office of Communications and Public Relations, Keio University
TEL: +81- 3-5427-1541
FAX: +81- 3-5441-7640
Email: m-koho@adst.keio.ac.jp
http://www.keio.ac.jp/
Ms. Mizue, Public Relations Office, Kyushu University
TEL: +81- 92-642-2106
FAX: +81- 92-642-2113
E-Mail: koho@jimu.kyushu-u.ac.jp
http://www.kyushu-u.ac.jp/
For more information concerning researches, get in touch with;
Prof. Shigeru Watanabe, Department of Psychology, Faculty of Letters, Keio University
E-Mail: swat@flet.keio.ac.jp
Kazuhiro Goto, Human Brain Research Center, Kyoto University
TEL: +81- 75-751-3692, +81- 90-5805-0489 FAX: +81- 75-751-3202
E-Mail: kgoto@psy.flet.keio.ac.jp
Isao Ito, Department of Biology, Faculty of Science, Kyushu University
TEL: +81- 92-642-2631, +81- 90-9475-5466 FAX: +81- 92-642-2645
E-Mail: isitoscb@kyushu-u.org
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Fig 1.
Schematic drawing of human brain (right hemisphere). Hippocampus plays important roles in
memory formation and spatial navigation.
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Fig 2.
Schematic drawing of mouse brain and hippocampal circuitry. Hippocampal asymmetry
was found in the circuitry formed by pyramidal neurons in area CA3 and CA1.
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Fig 3.
Hippocampal asymmetry and right isomerism of the iv/iv mouse hippocampus. Left
and right CA3 pyramidal neurons and their axons are colored red and blue, respectively.
A postsynaptic CA1 pyramidal neuron is at the center, colored black, and it represents
postsynaptic neurons in both left and right hemispheres. Closed and open circles
represent NR2B-dominant and NR2B-nondominant synapses, respectively. Apical,
apical dendrites; Basal, basal dendrites.
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Fig 4.
Exploratory behavior while searching a baited food. The coarse spatial distribution of
exploratory behaviors. Orange circles indicate the location of the food-baited hole. The
exploratory behavior of the iv/+ mice was more focused around the baited hole,
whereas it was less focused in iv/iv mice.
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Fig 5.
Schematic illustration of apparatus and experimental procedure. (A) The front and
back
panel
of
the
operant
conditioning
chamber,
and
(B)
the
delayed
nonmatching-to-position task sequence. (C) This gragh shows how fast mice forget the
remembered lever position over delay interval (x-axis). Although the mutant mice
initially showed as good memory as the control mice, their memory decay more rapidly
than the control mice.
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