Shigemoto, RyuichiISTA ; Kinoshita, Ayae; Wada, Eiki; Nomura, Sakashi; Ohishi, Hitoshi; Takada, Masahiko; Flor, Peter; Neki, Akio; Abe, Takaaki; Nakanishi, Shigetada; Mizuno, Noboru
Neurotransmission in the hippocampus is modulated variously through presynaptic metabotropic glutamate receptors (mGluRs). To establish the precise localization of presynaptic mGluRs in the rat hippocampus, we used subtype-specific antibodies for eight mGluRs (mGluR1-mGluR8) for immunohistochemistry combined with lesioning of the three major hippocampal pathways: the perforant path, mossy fiber, and Schaffer collateral. Immunoreactivity for group II (mGluR2) and group III (mGluR4a, mGluR7a, mGluR7b, and mGluR8) mGluRs was predominantly localized to presynaptic elements, whereas that for group I mGluRs (mGluR1 and mGluR5) was localized to postsynaptic elements. The medial perforant path was strongly immunoreactive for mGluR2 and mGluR7a throughout the hippocampus, and the lateral perforant path was prominently immunoreactive for mGluR8 in the dentate gyrus and CA3 area. The messy fiber was labeled for mGluR2, mGluR7a, and mGluR7b, whereas the Schaffer collateral was labeled only for mGluR7a. Electron microscopy further revealed the spatial segregation of group II and group III mGluRs within presynaptic elements. Immunolabeling for the group III receptors was predominantly observed in presynaptic active zones of asymmetrical and symmetrical synapses, whereas that for the group II receptor (mGluR2) was found in preterminal rather than terminal portions of axons. Target cell-specific segregation of receptors, first reported for mGluR7a (Shigemoto et al., 1996), was also apparent for the other group III mGluRs, suggesting that transmitter release is differentially regulated by 2-amino- 4-phosphonobutyrate-sensitive mGluRs in individual synapses on single axons according to the identity of postsynaptic neurons.
Journal of Neuroscience
This work was supported by research grants from the Inamori Foundation and the Ministry of Education, Science, Sports and Culture of Japan. We thank Peter Somogyi for helpful discussion, David Roberts for technical assistance, and Akira Uesugi for photographic assistance. We are grateful to Atsu Aiba, David Hampson, John Roder, and Herman van der Putten for providing us with mGluR1-, mGluR4-, mGluR5-, and mGluR7-deficient mice, respectively, and to Corrado Corti and Francesco Ferraguti for sharing rat mGluR8 cDNA and unpublished results.
7503 - 7522
Shigemoto R, Kinoshita A, Wada E, et al. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. Journal of Neuroscience. 1997;17(19):7503-7522. doi:10.1523/JNEUROSCI.17-19-07503.1997
Shigemoto, R., Kinoshita, A., Wada, E., Nomura, S., Ohishi, H., Takada, M., … Mizuno, N. (1997). Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.17-19-07503.1997
Shigemoto, Ryuichi, Ayae Kinoshita, Eiki Wada, Sakashi Nomura, Hitoshi Ohishi, Masahiko Takada, Peter Flor, et al. “Differential Presynaptic Localization of Metabotropic Glutamate Receptor Subtypes in the Rat Hippocampus.” Journal of Neuroscience. Society for Neuroscience, 1997. https://doi.org/10.1523/JNEUROSCI.17-19-07503.1997.
R. Shigemoto et al., “Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus,” Journal of Neuroscience, vol. 17, no. 19. Society for Neuroscience, pp. 7503–7522, 1997.
Shigemoto R, Kinoshita A, Wada E, Nomura S, Ohishi H, Takada M, Flor P, Neki A, Abe T, Nakanishi S, Mizuno N. 1997. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. Journal of Neuroscience. 17(19), 7503–7522.
Shigemoto, Ryuichi, et al. “Differential Presynaptic Localization of Metabotropic Glutamate Receptor Subtypes in the Rat Hippocampus.” Journal of Neuroscience, vol. 17, no. 19, Society for Neuroscience, 1997, pp. 7503–22, doi:10.1523/JNEUROSCI.17-19-07503.1997.
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