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Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in iv mice.

Goto K, Kurashima R, Gokan H, Inoue N, Ito I, Watanabe S - PLoS ONE (2010)

Bottom Line: Although left-right (L-R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior.To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively.These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.

View Article: PubMed Central - PubMed

Affiliation: Japan Society for the Promotion of Science, Tokyo, Japan. kgoto@psy.flet.keio.ac.jp

ABSTRACT
Although left-right (L-R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv) mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness) in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.

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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 ε2-dominant andε2-nondominant synapses, respectively. Apical, apical dendrites; Basal, basal dendrites.
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pone-0015468-g001: 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 ε2-dominant andε2-nondominant synapses, respectively. Apical, apical dendrites; Basal, basal dendrites.

Mentions: We have previously shown that the distribution of N-methyl-D-aspartate receptor (NMDAR) ε2 subunits in the mouse hippocampus is asymmetrical, both between synapses formed on the apical and basal dendrites of individual neurons and between synapses formed by inputs from the left and right pyramidal neurons (Figure 1, WT)[5], [6]. These asymmetrical allocations of ε2 subunits affect the properties of NMDARs in hippocampal synapses and generate two populations of synapses with complementary properties. One population consists of ‘ε2-dominant’ synapses, in which the NMDAR-mediated excitatory postsynaptic currents (NMDA EPSCs) show high sensitivity to Ro 25-6981, an ε2 subunit selective antagonist [7]–[9]; in this population, synaptic plasticity develops rather early. The other population consists of ‘ε2-nondominant’ synapses, in which the NMDA EPSCs are less sensitive to Ro 25-6981; in this population, synaptic plasticity develops slowly. These two populations of synapses are located asymmetrically in the hippocampal circuitry. We hypothesized that the synaptic distribution of ε2 subunits and the properties of NMDAR-mediated synaptic functions might be sensitive and quantitative indices for detecting abnormalities in the L−R asymmetry of the brain.


Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in iv mice.

Goto K, Kurashima R, Gokan H, Inoue N, Ito I, Watanabe S - PLoS ONE (2010)

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 ε2-dominant andε2-nondominant synapses, respectively. Apical, apical dendrites; Basal, basal dendrites.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2984506&req=5

pone-0015468-g001: 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 ε2-dominant andε2-nondominant synapses, respectively. Apical, apical dendrites; Basal, basal dendrites.
Mentions: We have previously shown that the distribution of N-methyl-D-aspartate receptor (NMDAR) ε2 subunits in the mouse hippocampus is asymmetrical, both between synapses formed on the apical and basal dendrites of individual neurons and between synapses formed by inputs from the left and right pyramidal neurons (Figure 1, WT)[5], [6]. These asymmetrical allocations of ε2 subunits affect the properties of NMDARs in hippocampal synapses and generate two populations of synapses with complementary properties. One population consists of ‘ε2-dominant’ synapses, in which the NMDAR-mediated excitatory postsynaptic currents (NMDA EPSCs) show high sensitivity to Ro 25-6981, an ε2 subunit selective antagonist [7]–[9]; in this population, synaptic plasticity develops rather early. The other population consists of ‘ε2-nondominant’ synapses, in which the NMDA EPSCs are less sensitive to Ro 25-6981; in this population, synaptic plasticity develops slowly. These two populations of synapses are located asymmetrically in the hippocampal circuitry. We hypothesized that the synaptic distribution of ε2 subunits and the properties of NMDAR-mediated synaptic functions might be sensitive and quantitative indices for detecting abnormalities in the L−R asymmetry of the brain.

Bottom Line: Although left-right (L-R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior.To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively.These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.

View Article: PubMed Central - PubMed

Affiliation: Japan Society for the Promotion of Science, Tokyo, Japan. kgoto@psy.flet.keio.ac.jp

ABSTRACT
Although left-right (L-R) asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B) subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv) mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness) in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP) task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.

Show MeSH