Neuronal major histocompatibility complex class I molecules are implicated in the generation of asymmetries in hippocampal circuitry

Aiko Kawahara, Shotaro Kurauchi, Yuko Fukata, José Martínez-Hernández, Terumi Yagihashi, Yuya Itadani, Rui Sho, Taiichi Kajiyama, Nao Shinzato, Kenji Narusuye, Masaki Fukata, Rafael Luján, Ryuichi Shigemoto, Isao Ito

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Abstract

Left-right asymmetry is a fundamental feature of higher-order brain function; however, the molecular basis of brain asymmetry has remained unclear. We have recently demonstrated asymmetries in hippocampal circuitry resulting from the asymmetrical allocation of NMDA receptor (NMDAR) subunit GluRe{open}2 (NR2B) in pyramidal cell synapses. This asymmetrical allocation of e{open}2 subunits affects the properties of NMDARs and generates two populations of synapses, 'e{open}2-dominant' and 'e{open}2-non-dominant' synapses, according to the hemispheric origin of presynaptic inputs and cell polarity of the postsynaptic neurone. To identify key regulators for generating asymmetries, we analysed the hippocampus of β2-microglobulin (β2m)-deficient mice lacking cell surface expression of major histocompatibility complex class I (MHCI). Although MHCI proteins are well known in the immune system, accumulating evidence indicates that MHCI proteins are expressed in the brain and are required for activity-dependent refinement of neuronal connections and normal synaptic plasticity. We found that β2m proteins were localised in hippocampal synapses in wild-type mice. NMDA EPSCs in β2m-deficient hippocampal synapses receiving inputs from both hemispheres showed similar sensitivity to Ro 25-6981, an e{open}2 subunit-selective antagonist, with those in 'e{open}2-dominant' synapses for both the apical and basal synapses of pyramidal neurones. The structural features of the β2m-deficient synapse in addition to the relationship between the stimulation frequency and synaptic plasticity were also comparable to those of 'e{open}2-dominant' synapses. These observations indicate that the β2m-deficient hippocampus lacks 'e{open}2-non-dominant' synapses and circuit asymmetries. Our findings provide evidence supporting a critical role of MHCI molecules for generating asymmetries in hippocampal circuitry.

Original languageEnglish
Pages (from-to)4777-4791
Number of pages15
JournalJournal of Physiology
Volume591
Issue number19
DOIs
Publication statusPublished - Oct 1 2013

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Major Histocompatibility Complex
Synapses
Neuronal Plasticity
Pyramidal Cells
Hippocampus
Brain
Cell Polarity
Proteins
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Immune System
Neurons

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Kawahara, A., Kurauchi, S., Fukata, Y., Martínez-Hernández, J., Yagihashi, T., Itadani, Y., ... Ito, I. (2013). Neuronal major histocompatibility complex class I molecules are implicated in the generation of asymmetries in hippocampal circuitry. Journal of Physiology, 591(19), 4777-4791. https://doi.org/10.1113/jphysiol.2013.252122

Neuronal major histocompatibility complex class I molecules are implicated in the generation of asymmetries in hippocampal circuitry. / Kawahara, Aiko; Kurauchi, Shotaro; Fukata, Yuko; Martínez-Hernández, José; Yagihashi, Terumi; Itadani, Yuya; Sho, Rui; Kajiyama, Taiichi; Shinzato, Nao; Narusuye, Kenji; Fukata, Masaki; Luján, Rafael; Shigemoto, Ryuichi; Ito, Isao.

In: Journal of Physiology, Vol. 591, No. 19, 01.10.2013, p. 4777-4791.

Research output: Contribution to journalArticle

Kawahara, A, Kurauchi, S, Fukata, Y, Martínez-Hernández, J, Yagihashi, T, Itadani, Y, Sho, R, Kajiyama, T, Shinzato, N, Narusuye, K, Fukata, M, Luján, R, Shigemoto, R & Ito, I 2013, 'Neuronal major histocompatibility complex class I molecules are implicated in the generation of asymmetries in hippocampal circuitry', Journal of Physiology, vol. 591, no. 19, pp. 4777-4791. https://doi.org/10.1113/jphysiol.2013.252122
Kawahara, Aiko ; Kurauchi, Shotaro ; Fukata, Yuko ; Martínez-Hernández, José ; Yagihashi, Terumi ; Itadani, Yuya ; Sho, Rui ; Kajiyama, Taiichi ; Shinzato, Nao ; Narusuye, Kenji ; Fukata, Masaki ; Luján, Rafael ; Shigemoto, Ryuichi ; Ito, Isao. / Neuronal major histocompatibility complex class I molecules are implicated in the generation of asymmetries in hippocampal circuitry. In: Journal of Physiology. 2013 ; Vol. 591, No. 19. pp. 4777-4791.
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