BDNF occludes GABAB receptor-mediated inhibition of GABA release in rat hippocampal CA1 pyramidal neurons

Authors

  • Yoshito Mizoguchi,

    1. Division of Homeostatic Development, Department of Developmental Physiology, National Institute of Physiological Sciences, 38 Myodaiji, Okazaki 444-8585 Japan
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    • *

      Y.M. and A.K. contributed equally to this work.

  • Akihiko Kitamura,

    1. Division of Homeostatic Development, Department of Developmental Physiology, National Institute of Physiological Sciences, 38 Myodaiji, Okazaki 444-8585 Japan
    2. CREST, the Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
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    • *

      Y.M. and A.K. contributed equally to this work.

  • Hiroaki Wake,

    1. Division of Homeostatic Development, Department of Developmental Physiology, National Institute of Physiological Sciences, 38 Myodaiji, Okazaki 444-8585 Japan
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  • Hitoshi Ishibashi,

    1. Department of Cellular Physiology, Faculty of Medicine Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka, 812-8582, Japan
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  • Miho Watanabe,

    1. Division of Homeostatic Development, Department of Developmental Physiology, National Institute of Physiological Sciences, 38 Myodaiji, Okazaki 444-8585 Japan
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  • Takuya Nishimaki,

    1. Division of Homeostatic Development, Department of Developmental Physiology, National Institute of Physiological Sciences, 38 Myodaiji, Okazaki 444-8585 Japan
    2. Department of Biological Sciences, Sokendai, 38 Myodaiji, Okazaki 444-8585, Japan
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  • Junichi Nabekura

    1. Division of Homeostatic Development, Department of Developmental Physiology, National Institute of Physiological Sciences, 38 Myodaiji, Okazaki 444-8585 Japan
    2. CREST, the Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan
    3. Department of Biological Sciences, Sokendai, 38 Myodaiji, Okazaki 444-8585, Japan
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Dr J. Nabekura, 1Division of Homeostatic Development, as above.
E-mail: nabekura@nips.ac.jp

Abstract

During the development of the rat hippocampus, both γ-aminobutyric acid (GABA)B autoreceptors and brain-derived neurotrophic factor (BDNF) play important roles in the formation of GABAergic synapses as well as in the GABAA receptor-mediated transmissions. While a number of studies have reported rapid effects of BDNF on GABAA receptor-mediated responses, the interactions between GABAB autoreceptors and BDNF are less clear. Using conventional whole-cell patch-clamp recordings, we demonstrated here that BDNF significantly occludes baclofen-induced suppression of GABAA receptor-mediated transmissions in each of the preparations including hippocampal slices prepared from P14 rats, hippocampal CA1 pyramidal neurons isolated from P14 and P21 rats, and cultured hippocampal pyramidal neurons. This effect of BDNF was rapid and reversible, and was mediated via the activation of presynaptic TrkB receptor tyrosine kinases, and subsequent activation of phospholipase C and protein kinase C. On the contrary, in hippocampal CA1 pyramidal neurons isolated from P7 rats, BDNF failed to occlude the GABAB receptor-mediated inhibition of GABA release. Thus, the ability of BDNF to occlude the GABAB receptor-mediated inhibition of GABA release develops between P7 and P14. This demonstrates a novel aspect of the effects of BDNF on inhibitory transmissions in rat hippocampus, which may have some functional roles in the induction of developmental plasticity and/or pathophysiology of epilepsy.

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