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Distinct localization of GABAB receptors relative to synaptic sites in the rat cerebellum and ventrobasal thalamus

Authors

  • Ákos Kulik,

    1. Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
    2. CREST, Japan Science and Technology Corporation, Kawaguchi, Japan
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    • *

      Present address: Department of Anatomy, University of Freiburg, 79114 Freiburg, Germany.

  • Kazuhiko Nakadate,

    1. Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
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  • Gábor Nyíri,

    1. Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
    2. CREST, Japan Science and Technology Corporation, Kawaguchi, Japan
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  • Takuya Notomi,

    1. Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
    2. Department of Physiological Sciences, the Graduate University for Advanced Studies, Myodaiji, Okazaki 444-8585, Japan
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  • Barbara Malitschek,

    1. Novartis Pharma Inc., Therapeutic Area Nervous System, CH-4002 Basel, Switzerland
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  • Bernhard Bettler,

    1. Novartis Pharma Inc., Therapeutic Area Nervous System, CH-4002 Basel, Switzerland
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  • Ryuichi Shigemoto

    1. Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan
    2. CREST, Japan Science and Technology Corporation, Kawaguchi, Japan
    3. Department of Physiological Sciences, the Graduate University for Advanced Studies, Myodaiji, Okazaki 444-8585, Japan
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: Dr Ryuichi Shigemoto, 1Division of Cerebral Structure, as above.
E-mail: shigemot@nips.ac.jp

Abstract

Metabotropic γ-aminobutyric acid receptors (GABABRs) are involved in modulation of synaptic transmission and activity of cerebellar and thalamic neurons. We used subtype-specific antibodies in pre- and postembedding immunohistochemistry combined with three-dimensional reconstruction of labelled profiles and quantification of immunoparticles to reveal the subcellular distribution of pre- and postsynaptic GABABR1a/b and GABABR2 in the rat cerebellum and ventrobasal thalamus. GABABR1a/b and R2 were extensively colocalized in most brain regions including the cerebellum and thalamus. In the cerebellum, immunoreactivity for both subtypes was prevalent in the molecular layer. The most intense immunoreactivity was found in Purkinje cell spines with a high density of immunoparticles at extrasynaptic sites peaking at around 240 nm from glutamatergic synapses between spines and parallel fibre varicosities. This is in contrast to dendrites at sites around GABAergic synapses where sparse and random distribution was found for both subtypes. In addition, more than one-tenth of the synaptic membrane specialization of spine–parallel fibre synapses were labelled at pre- or postsynaptic sites. Weak immunolabelling for both subtypes was also seen in parallel fibres but only rarely in GABAergic axons. In the ventrobasal thalamus, immunolabelling for both receptor subtypes was intense over the dendritic field of thalamocortical cells. Electron microscopy demonstrated an extrasynaptic localization of GABABR1a/b and R2 exclusively in postsynaptic elements. Quantitative analysis further revealed the density of GABABR1a/b around GABAergic synapses was higher than glutamatergic synapses on thalamocortical cell dendrites. The distinct localization of GABABRs relative to synaptic sites in the cerebellum and ventrobasal thalamus suggests that GABABRs differentially regulate activity of different neuronal populations.

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