東北大学医学部 - 東北大学大学院医学系研究科・新医学領域創生分野
Contents
1. CRNERESIESERES Aes e ORNA2. 6 5 1 36 ETATE SA ICTUUTR LA TZVAI
3. Occ CC 2 Calyx of Held
4. 7 8 2 ChR2
5. E vL Me 10 pA miniature EPSC PostSynaptic Current i miniature EPSC excitatory postsynaptic current
6. NMDA PAREC NMDA Ca Long term potentiation LTP A Schaffer collateral pathway LTP Kom AIERT AL ar R 30 APV NMDA NMDA
7. cx p C deen wy c elegans undi ui cc ITCH C elegans 1 mm 302 50 nm 8000 10 1986 340 1 302
8. Co ETIN ey OL 0 6 er P x 1 ws 28 36 EAT UE SA ICTUUTqR LA T VAI 1
9. 00 SE E 1000 1000 1 30 13k 2003
10. AMPA Var ATC evs ic AMPA 7 1 wes E PPR 0 50 PPR 0 22 42 7 Open MODEL 217 AMPA 10 Open 0 1 AMPARs 32 Open Control CTZ yDGG DATA Budisantoso TW ae 2012 J Neurosci
11. 34 36 ETAT UE SA ICTUUTR LA TZVAI id Budisantoso T Harada H Kamasawa N Fukazawa Y Shigemoto R Matsui K 2013 Evaluation of glutamate concentration transient in the synaptic cleft of the rat calyx of Held Journal of Physiology 591 219 239 corresponding author Sasaki T Beppu K Tanaka KF Fukazawa Y Shigemoto R Matsui K 2012 Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation Proc Natl Acad Sci U S A 109 20720 20725 equal contribution corresponding author Tanaka KF Matsui K Sasaki T Sano H Sugio S Fan K Hen R Nakai J Yanagawa Y Hasuwa H Okabe M Deisseroth K Ikenaka K Yamanaka A 2012 Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system Cell Reports 2 397 406 equal contribution Budisantoso T Matsui K Kamasawa N Fukazawa Y Shigemoto R 2012 Mechanisms underlying signal filtering at a multi synapse contact Journal of Neuroscience 32
12. AMPA AMPA Rr il 1 30 36 EAGET UE SA ICTUUTqR LA TZVAI AMPA
13. 19 36 ETATE SA ICTUUTqR LA TZVAI Concentration Diffusion Synapse Calyx of Held M Satzjer et al 2002 La N D Calyx of Held EN
14. ChR2 C128S ChR2 100 ChR2 ieee MM Ta ChR2 ChR2 1000 1 2
15. 50 Hz a em CFF 31 36 EAE UE SA ICTUUTR LA TZZAI 16
16. cross fracture uo ND oa IRO WET SDS digested fre freeze fracture repica of pane of Held synapse _ 21 36 EAE XA LGTWUTqR LIA cM ZAI AMPA 2
17. C r t 4ATthtD 2 e 7m r t h 20 nm gt gt 20 36 EAE UE SA ILGTUUTqR LA TAVAI cross fracture P face P face E face postsynaptic density PSD AMPA calyx of Held
18. AMPA AMPA 16 36 EAT UE Outsige out 2 ACSF 10 mM Glu yam p AMPA ae f n
19. darcy TUO oU XL HRS Docking Priming SNARE SNARE 33607 C4 Ca SNARE complex 2 1
20. 6 36 EAE S IcTUUTqR LA TZZAI 3 Ca Ca MPS WA SELL E HER Ca Ca
21. MEUS WM
22. AMPA LGN AMPA Critical Flicker Frequency
23. 302 10001 1 1 70 nm 100
24. ent ME at oma endocytosis t ED Cos exocytosis endocytosis motio fg re tum c Transmissio arduo r Retina Paired ings of Bipolar Cells end Neu uron of the Gan seht n Cell Layer o Matsui Nobutake Hosoi and Masao Tachibana Rise time ms oO M e GD 9 36 ETATE SA IcTUUTR LA TAZAI 198090 esicle Endocytosis Requires tiyinni a Peat CNS Syrpa o DSJ RU ESTEET 7 JANUARY 2005 VOL307 SCIENCE
25. 10 ms asma A 0 AMPA ni AMPA MODEL ORO O E uve jme 17 36 EAE UE SA IcTUUTqR LA TZVAI 9
26. N x Pr Q N x Pr x Q CON Pr Q N Pr N x Pr Q v N x Pr x Q JL i E N x Pr x Q d amp 0 003
27. N D lt IMG ee ial ee N D ea N 7000 D 0 3 Tv C EAE UIT N 7000 D 0 3 um ms 23 36
28. 10 ELI TEM FIB SEM EMMA E Loc ES EMME gt gt TO E DERE EL m 99 Slicing ar Ze y a S S FIB SEM Pe FIB focused ion beam OW nm trans electron microscope TEM
29. 0 4 SDS 2 AMPA m Memes terminal ooo X Ys Presynaptic SDS FRL Presynaptic P face Postsynaptic sit
30. active zone docking priming 10 36 ETAT UE SA IGTUUTR LA TZVAI SNARE Late endosome E vesicle lysosome recursor 2c A Turnover of plasma membrane proteins i pip s e Neurotransmitter gt uptake Qu Clathrin Kiss and run I vesicle 28 Fission ED Ca endocytosis SNARE Synaptobrevin VAMP vesicle SNARE
31. 0 5 0 6 HEA OM WATIE 7 4 AMPA 2 Le 29 36 ETATE SA ICTUUTqR LA TZVAI 7 217 AMPA
32. IE OU RE 2 90 pr Ca
33. 2 B nm NET post synaptic density
34. Outside out AMPA outside out AMPA AMPA 2 4 ms ms 2 URED OO 140
35. 2 2 serial block face SEM NN 0 x 6 30 nm 300
36. 32 AMPA 7 AMPA 1 4 2 2 paired pulse ratio X 0 5 32 7 AMPA paired pulse ratio 0 22 42 AMPA SLE AMPA
37. tTA 2 ChR2 KENGE tet system tTA mouse
38. SER HET ICO WT ChR2 ChR2 BUC SERRLET ChR2 Jk Chlamydomonas Light sensitive protein Electrophysiological recording from Channelrhodopsin 2 ChR2 a neuron expressing modified ChR2 C128S ChR2 naka Matsui et al 2012 Cell Reports ChR2 ChR2 32 36 EAT UM SA ICTUUTqR LA TZZAI ChR2 ChR2 BYFP ChR2
39. th LOO xD ur 2 Ca pom WWW Sop 3 Ca Ca Ca Ca Ca ECL ii BC AAEE n she cotta GLC mi TBO Ca n nt SL dL uu WV deer me ers so pA SN GLC
40. AnhtD 2 zIN am 4rp ArThtD 11 N x Pr x Q N x Pr x Q Mean Variance Analysis N Pr Q N Pr
41. ChR2 KENGE tet system 7 tTA tetO tTA miror RIDGE of transgenic mice Mee eT 57 UE F CT eaGamkll Orexin Iba1 tetO ChR2 tetO ChR2 dd B actin DNA kenn DNA B actin
42. E EET NI 10 pA v sf 200 ms 7 36 EAT UE SA ICTUUTR LA TAVAI Ca Ca Ca Ca 1 Ca WE E PEE Ca Ca 6o Ca Co Ca
43. Synaptotagmin 12 36 ETATE SA ICTUUTqR LA TAVAI 6 2 2 To AMPFA NMDA AMPA AMPA Na ae nce e MM
44. 1 AMPA 15 Hil
45. Ca Coz caged Ca Ca caged Ca UV J Ca BRR AS IC Ca caged Ca UV Ca Ca Ca C Ca Ca eee aptic Transmission in the Inner Retina Paired dings of Bipolar Cells a and Hewone of the Ganglion Cell Layer o Matsui Nobutake Ho and Masao Tachibana A B C Control Co Washout n n y i BC
46. 40 mV ORE Me NMDA 0 mV 20 mV NMDA 14 36 EAT XA IT WUMqR L A ME ZAI 7 Ca
47. LTP AMPA NMDA Mge NMDA Ca Ca calmodulin Ca calmodulin CamKII DS AMPA AMPA UC Ca ca
48. serial electron microscope SEM FB FIB SEM 1 2 4 36 EAT UE SA ICTUUTR LA TAVAI SEM 5 serial block face SEM 1 2
49. 0 ae I COL GL CeO ies S9 V7 FAO PE DE Ta OM 00 N D N 7000 D 0 3 um ms AMPA Outside out Diffusion Equation e 4tD 4nhtD C r t N 7000 D 0 3 mms m o3 0 1M etc 0 04 ms a Open NS 2 ms I pA Open AMPARs x Y pS x V V 7 43 9 pA Receptor Kinetic Model
50. Ca 2 mM 0 61 0 61 MNTB calyx of Held 0 1 0 3 0 9 Pr release probability 0 2 mM Ca 0 61 o Matsui et al 20 12 2 paired pulse ratio PPR T PPR N Pr Q
51. MENS NED N 7000 D 0 3 N EFRELYF 22 36 N D N ED N D
52. Markov AMPA p LGN We T in T J Glutamate 5 ms MODEL r 2 4 ms Glu Glu adim di Y Ost N UNS _ Poo2 Budisantoso Matsui et al 2012 Neurosci DATA dudi wah eam 50 ms 27 36 EFREFEOSF 88 A 1 4
53. SDS FRL Extracellular Surface Intracellular Surface SDS FRL Extracellular we v Pt C deposition Freeze fracture 1 SA e E Replica SDS treatment p ag J P face Intracellular Immunogold secondary antibody SDS FRL i ibody inst EXTRAcellular domain E face Extracellular Intracellular Primary antibody against INTRAcellular domain Immunogold secondary antibody 18 36 ET AET UTE i Ha
54. N x Pr x Q N x Pr N N x Pr Pr 25 36 ETATE S4 IcTUUTqR LA TZVAI Paired Pulse Ratio PPR N Q PPR 1 Pr Mean Variance Analysis Pr 0 61 PPR 0 39 us 13 RG stim RC response PPR EPSC EPSC 40 1 Pr 6 1 0 61 0 39 40 NxPrxQ 2 N NxPr xPrxQ
55. 30 5 36 ETAT UE SA IcTUUTR LA TAZAI MRI TEE offusion spectrum imacine MRI MRI fMRI fMRI
56. 11 36 EAT UE SA IcTUUTR LA TZVAI SNARE V SNARE Synaptobrevin VAMP SynaptobrevirV Zippering Syntaxin SNARE complex t SNARE SNAP 25 Synatxin Ca Synaptotagmin Ch Ca C2 2 Synaptotagmn galas Synaptotagmin
57. vY SNARE SNAP 2S Syntaxin tSNARE SNARE core complex coiled coil zippering Ca SNARB complex SNARE complex SNAP NSF ATP complex endocytosis
58. Mean N x Prx 4j li Variance N x ded 1 P xQ S ie V QxM M2N V M 0 02 04 06 08 1 12 14 Mean nA NxQ M V Qx thse OME O Pr 1 M Nx1xQ Mean Variance Analysis V M C M M V Q 24 36 ETAT UE SA ICTUUTR LA TZVAI x M Q Pr 1 M N x Q V 0 X N XQ Q N N
59. NeERT DFTA IMMERSES ge NMDA AMPA NMDA NMDA Movil id NMDA m Mg ck During depolarization NMDA RAITZ MrJ INAN NMDA Resting membr Ca potential During depolarization 1 NMDA Mg N AMPFA amp GARTKEIRIUS Na vA EO NMDA Na iain NMDA 13
60. Q Pr Mean Variance Analysis Bu ow Y Y f 3 x l Sms N Pr Q EN Quantal EPSC 17 pA JAN 17 pA b 1 ee a Sr O susan Mati a 2012 Neurose 10 20 pA 71
61. 36 EAE UTE SA ICTUUTqR LA TZVAI A Early and late components of synaptic current B Current voltage relationship of the synaptic current Peak current Late current Membrane potential 4 APV Q Late current 20 mV with APV Late current without APV 100 pA 150 100 40 mV Peak early A current Without APV with APV Peak early A current without APV With APV N Without APV 80 mV NMDA APV 40 mV NMDA APV NMDA
62. PSD PSD 2 36 ETATE SA ICTUUTL LA TAZAI E e p gt RS SE SEINEN ed ht e gt 3 36 EAT UE S ICTUUTqR LA TAVAI H2 Fo
63. 2357 2376 equal contribution corresponding author Tarusawa E Matsui K Budisantoso T Moln r E Watanabe M Matsui M Fukazawa Y Shigemoto R 2009 Input specific intrasynaptic arrangements of ionotropic glutamate receptors and their impact on postsynaptic responses Journal of Neuroscience 29 12896 12908 corresponding authors Matsui K Hosoi N Tachibana M 1998 Excitatory synaptic transmission in the inner retina paired recordings of bipolar cells and neurons of the ganglion cell layer Journal of Neuroscience 18 4500 4510 2013 SERRE 31 1712 1717 2013 BRAIN and NERVE 65 609 621 JK 2013 Clinical Neuroscience 31 24 26 2012 OplusE 396 1085 1090 CREA ay 2008 EJ E H ETE BEBESE 53 435 441 Bollmann JH Sakmann B Borst JG Calcium sensitivity of glutamate release in a calyx type terminal Sc
64. ia 100 pA ys AT el pw GLC 300 ms Ca Calcium Sensitivity of Glutamate Release in a Calyx Type E johann H Bollmann Bert Sakmann C Bore SCIENCE VOL 289 11 AUGUST 2000 Photocleavage OOC COO Ca je FE ae lt iL 8 36 EAT UE SA IcTUUTR LA TAZAI Eq 4 30 nm 1 2
65. 995 Jun 22 375 6533 645 53 Sutton RB Fasshauer D Jahn R Brunger AT Crystal structure of a SNARE complex involved in synaptic exocytosis at 2 4 A resolution Nature 1998 Sep 24 395 6700 347 53 Walmsley B Alvarez FJ Fyffe RE Diversity of structure and function at mammalian central synapses Trends Neurosci 1998 Feb 21 2 81 8 White JG Southgate E Thomson JN Brenner S The structure of the nervous system of the nematode Caenorhabditis elegans Philos Trans R Soc Lond B Biol Sci 1986 Nov 12 314 1165 1 340 Yamashita T Hige T Takahashi T Vesicle endocytosis requires dynamin dependent GTP hydrolysis at a fast CNS synapse Science 2005 Jan 7 307 5706 124 7 Principles of Neural Science Eric R Kandel James H Schwartz Thomas M Jessell McGraw Hill Health Professions Division Synapses W Maxwell Cowan Thomas C S dhof Charles F Stevens The Johns Hopkins University Press http www technologyreview com biomedicine 21175 pagel 36 36 ETATE SA IcTUUTR LA TZZAI
66. RY 2013 12 12 ie 8 50 12 10 GB matsui med tohoku acJp http www ims med tohoku acjp matsui 8208 1 e SCS TA Min XB
67. e AMPA ELS 10 VIDA MRO a zmBI dUc qmxT87J54z278 2 C0 amp 5U 0E N D 2 outside out
68. ience 2000 Aug 11 289 5481 953 7 Geppert M Goda Y Hammer RE Li C Rosahl TW Stevens CF S dhof TC Synaptotagmin I a major Ca2 sensor for transmitter release at a central synapse Cell 1994 Nov 18 79 4 717 27 35 36 EFREFEOF SEA IGTWUTMAR IA TZZAI Heuser JE Reese TS Structural changes after transmitter release at the frog neuromuscular junction J Cell Biol 1981 Mar 88 3 564 80 Heuser JE Reese TS Dennis MJ Jan Y Jan L Evans L Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release J Cell Biol 1979 May 81 2 275 300 Jahn R Fasshauer D Molecular machines governing exocytosis of synaptic vesicles Nature 2012 Oct 11 490 7419 201 7 doi 10 1038 nature11320 Malenka RC Nicoll RA Long term potentiation a decade of progress Science 1999 Sep 17 285 5435 1870 4 Morgan SL Teyler TJ Electrical stimuli patterned after the theta rhythm induce multiple forms of LTP J Neurophysiol 2001 Sep 86 3 1289 96 Rizo J S dhof TC Snares and Munc18 in synaptic vesicle fusion Nat Rev Neurosci 2002 Aug 3 8 641 53 Satzler K S hl LF Bollmann JH Borst JG Frotscher M Sakmann B L bke JH Three dimensional reconstruction of a calyx of Held and its postsynaptic principal neuron in the medial nucleus of the trapezoid body J Neurosci 2002 Dec 15 22 24 10567 79 S dhof TC The synaptic vesicle cycle a cascade of protein protein interactions Nature 1
69. lmodulin PKC 15 36 ETATE SA ICTUUTR LA T ZZAI AMPA 5E LTP AMPA AMPA lt VIPFARMA E Buoy jo uoiSSeJdx3 9 uonenuejod wuel Buoj jo uononpuj g uongnuejod wal e lt a 94 Go Vi vin ag f x zO RO elis outside out outside out
70. ms Outside out Vetthiritbkapli c 1 ACSF 10 mM Glu Outside out ACSF 10 mM Glu i Ooo E 1 qM ue 5 ms xc 2 4 ms PTT 50 ms 140 ms AMPA 26 36 ETATE S IcTUUTR LA TZVAI LGN S B o 2 pA a 20 pA 5 ms 20 ms 2 4 ms 5 3 5 4 ms AMPA AMPA 30 ms AMPA
71. tetO ChR2 mouse 33 36 EAT UE SA IcTUUTqR LA T ZVAI Brain circuit di IL ide or iiaii 1 a GF ChR2 Mii d de e A gt XC EM EPIS AS ariel 3 E La j UN 2n 2 Cal circuit GBS E Opticalimaging jJMeae med
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