医学部 薬理学講座

丹羽 史尋

ニワ フミヒロ  (Fumihiro Niwa)

基本情報

所属
自治医科大学 医学部 薬理学講座 分子薬理学部門 助教
学位
博士(生命科学)(2012年6月 東京大学)

研究者番号
50641974
ORCID ID
 https://orcid.org/0000-0002-0206-1902
J-GLOBAL ID
201901007485494529
researchmap会員ID
B000360233

主要な論文

 13
  • Fumihiro Niwa
    iScience 22 453-465 2019年11月  査読有り筆頭著者
  • Hiroko Bannai, Fumihiro Niwa, Mark W. Sherwood, Amulya Nidhi Shrivastava, Misa Arizono, Akitoshi Miyamoto, Kotomi Sugiura, Sabine Levi, Antoine Triller, Katsuhiko Mikoshiba
    CELL REPORTS 13(12) 2768-2780 2015年12月  査読有り筆頭著者
    GABAergic synaptic transmission regulates brain function by establishing the appropriate excitation-inhibition (E/I) balance in neural circuits. The structure and function of GABAergic synapses are sensitive to destabilization by impinging neurotransmitters. However, signaling mechanisms that promote the restorative homeostatic stabilization of GABAergic synapses remain unknown. Here, by quantum dot single-particle tracking, we characterize a signaling pathway that promotes the stability of GABA(A) receptor (GABA(A)R) postsynaptic organization. Slow metabotropic glutamate receptor signaling activates IP3 receptor-dependent calcium release and protein kinase C to promote GABA(A)R clustering and GABAergic transmission. This GABA(A)R stabilization pathway counteracts the rapid cluster dispersion caused by glutamate-driven NMDA receptor-dependent calcium influx and calcineurin dephosphorylation, including in conditions of pathological glutamate toxicity. These findings show that glutamate activates distinct receptors and spatiotemporal patterns of calcium signaling for opposing control of GABAergic synapses.
  • Fumihiro Niwa, Hiroko Bannai, Misa Arizono, Kazumi Fukatsu, Antoine Triller, Katsuhiko Mikoshiba
    PLOS ONE 7(4) e36148 2012年4月  査読有り筆頭著者
    The activity-dependent modulation of GABA-A receptor (GABA(A)R) clustering at synapses controls inhibitory synaptic transmission. Several lines of evidence suggest that gephyrin, an inhibitory synaptic scaffold protein, is a critical factor in the regulation of GABA(A)R clustering during inhibitory synaptic plasticity induced by neuronal excitation. In this study, we tested this hypothesis by studying relative gephyrin dynamics and GABA(A)R declustering during excitatory activity. Surprisingly, we found that gephyrin dispersal is not essential for GABA(A)R declustering during excitatory activity. In cultured hippocampal neurons, quantitative immunocytochemistry showed that the dispersal of synaptic GABA(A)Rs accompanied with neuronal excitation evoked by 4-aminopyridine (4AP) or N-methyl-D-aspartic acid (NMDA) precedes that of gephyrin. Single-particle tracking of quantum dot labeled-GABA(A)Rs revealed that excitation-induced enhancement of GABA(A)R lateral mobility also occurred before the shrinkage of gephyrin clusters. Physical inhibition of GABA(A)R lateral diffusion on the cell surface and inhibition of a Ca2+ dependent phosphatase, calcineurin, completely eliminated the 4AP-induced decrease in gephyrin cluster size, but not the NMDA-induced decrease in cluster size, suggesting the existence of two different mechanisms of gephyrin declustering during activity-dependent plasticity, a GABA(A)R-dependent regulatory mechanism and a GABA(A)R-independent one. Our results also indicate that GABA(A)R mobility and clustering after sustained excitatory activity is independent of gephyrin.

MISC

 3

講演・口頭発表等

 7

担当経験のある科目(授業)

 3

所属学協会

 4

共同研究・競争的資金等の研究課題

 9