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
1.2. Brain ci
3. Co EIC C codo D ST
4. AMPA AMPA Rr il 1
5. 50 Hz SE dnb CFF RLY 31 36 EAE UE SA ICTUUTR LA TZZAI
6. 30 nm 1 2 H NE i nn SEMI XE MINAS COLARL TOAL VAT m E Lunas ioni Gau Cv ev DUC
7. cx p wey ty c elegans undis uu 20288 cc ITCH C elegans 1 mm 302 50 nm 8000 10 1986 340 1 302
8. Se 1000 Sails sii 1000 1 30 13k 2003 30
9. KENGE tet system tTA mouse 33 36 EAT UE SA IcTUUTqR LA T ZVAI WIVES cO mege t VM EE 1 ChR2 Electrophyslology E E RE Eo dido n E j 1 f ANA E ST P
10. 16 7 8
11. gs dons EE OL on N D N D al zhtp Mu
12. Ca darcy TUO oU XL HRS Docking Priming SNARE SNA
13. NMDA APV 40 mV NMDA APV NMDA 40 mV ORE ALC Mg NMDA 0 mV 20 mV K NMDA 14 36 EAT XA
14. N D CN N 7000 D 0 3 W 700D 03yumms TV C co Cu 23 36 EAE UE SA TFYPLR LA 11 N x Pr x Q N x Pr x Q Mean Variance Analysis
15. outside out 19 36 ETATE SA ICTUUTqR LA TZVAI Concentration Diffusion Synapse Calyx of Held MNTB PN Satzler et al 2002 I ui Walmsley et al 1998 E 95 oq TREMO RIO ICH TS N D Calyx of Held
16. 2 ChR2 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 2 ChR2 naka Matsui et al 2012 Cell Reports ChR2
17. ED Ed 1 36 ETATE SA ICTUUTR LA TZVAI
18. 30 36 EAGET UE SA ICTUUTqR LA TZVAI AMPA AMPA LGN AMPA Critical Flicker Frequency
19. 6 36 EAE S IcTUUTqR LA TZZAI HE3 Ca Ca MPS OA ee E 4 M oso MEO mA SITE L NEBL LE BLA i a Li OM Vs mme Ca Ca
20. 302 AS CAA 1000 1 1 70 nm 100
21. 5 36 ETAT UE SA IcTUUTR LA TAZAI MRI TEE offusion spectrum imacine MRI MRI fMRI fMRI
22. e a EN Occ CS mU VCLEOS
23. 7 217 AMPA 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
24. 10 ELI TEM FIB SEM Jedes E E MMM a gt gt EE EE 00 27 238 0B 08 9 Fr ze VES LC x38 T p 72i Li 1 FIB SEM W FIB focused ion beam OK nm trans electron microscope TEM serial electron microsc
25. d AMPA NMDA AMPA AMPA Nr EN Mg g AER T Ee ae NMDA AMPA NMDA NMDA Movilidad NMDA m Mg lz d NMDA LEK Mg gt 4 tea
26. ChR2 1000 1 2 ChR2 KENGE tet system 7 tTA tetO tTA M eion et TREE of transgenic mice a amkll Orexin Mic Iba tetO ChR2 tetO ChR2 B actin
27. 28 36 EAT UE SA ICTUUTqR LA T VAI 1 AMPA Var ATC evs ic AMPA 7 1 velas be
28. AMPA 1 AMPA 15 EI
29. 2 B nm NET post synaptic density PSD
30. DNA kenn DNA B actin tTA 2 ChR2
31. Extracellular Surface Intracellular Extracellular 18 36 EAT UE SA IGTUUTR LA TZZAI Memes terminal ee R 2e o SDS FRL Presynaptic P face AMPA ELS 10 VIDA MRO a zmBI dUc qmxT87J54z278 23700 SU ORE N D 2
32. lt VLIPFARMA Bt SUBJ 2I1OeuUAS BUUJOMN V uonenuejod Wwue Hud jo UOI1OnPu g m Uu S 2 o e 2 c c 3 Q Q E 2 e o Sis outside out outside out AMPA AMPA 16 36 EAT UE
33. ms Outside out C B n IU 2 2 4 ms pm 7 T NL 140 ms ime T AMPA 26 36 ETATE S IcTUUTR LA TZVAI LGN EP cca NENNEN we S fam Z 20 pA 5 ms 20 ms c 2 4 ms c 5 3 5 4 ms AMPA T
34. AMPA AMPA MODEL Glu Glu kk Os a 17 36 EAE UE SA IcTUUTqR LA TZVAI A9 RS on ALAM UE CFB DIU CO Intracellular Surface
35. 2 2 serial block face SEM NN 0 x 6 30 nm 300
36. 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 Q Pr Mean Variance Analysis T dim um ow Y Y f 3 m sms N Pr Q de loai eg ANN 17 pA
37. N Pr Q N Pr N x Pr Q N x Pr x Q CON Pr Q u u NxPrxQ Ue
38. HEEL REIL UD SDS FRL y BU v o SZEORSICEoC S TREES W Puc 7 Oe IUOS CTUM des SDS treatment ff ee SDS REE FDR f mninga Intracellular M ANE remunogoldsecondary antibody AMPA
39. OF he iR Vae neon a pone B rm V QxM MN 0 02 04 oe 08 1 1 N Pr N x Pr Q v N xPrxQ V ZJAZIBb JL 0 006 Mean nA M NxQ M V Qx Kee Q Pr 1 M Nx1xQ Mean Variance Analysis V M C M MZ
40. Outside out gh ACSF 10 mM Glu yas Py AMPA 0 f oo ni 10 ms mema A
41. VI TAR FB Long term potentiation LTP EE A Schaffer collateral pathway LTP T ry BBE RUE TA ATTA 250 30 APV NMDA NMDA LTP AMPA
42. 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 Tt Matsui K Kamasawa N Fukazawa Y Shigemoto R 2012 Mechanisms underlying signal filtering at a multi synapse contact Journal of Neuroscience 32 2357 2376 equal contribution corresponding author Tarusawa E Matsui K Budisantoso T Molnar 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 n
43. SNARE complex SNARE complex X SNAP NSF ATP complex endocytosis 11 36 EAT UE SA IcTUUTR LA TZVAI SNARE V SNARE Synaptobrevin VAMP Synaptobrevin VAMP Zippering Nucleation vids SNARE complex t SNARE SNAP 25 Synatxin Ca Synaptotagmin Ch Ca C2 2 Synaptotagmn eal N
44. ChR2 32 36 EAT UM SA ICTUUTqR LA TZZAI ChR2 ChR2 EYFP ChR2 ChR2 C128S ChR2 100 ChR2 ieee MM Ta ChR2
45. b ey Sr todas Mati et at 20 Nen 10 20 pA 71 Ca RED 2 mM 0 61 0 61 MNTB calyx of Held 0 1 0 3 0 9 Pr release probability 2 mM Ca 0 61 o Matsui et al 2 12 2 paired pulse rati
46. E face postsynaptic density PSD AMPA calyx of Held cross fracture m cross fracture SDS digested freeze fracture replica of calyx of Held synapse _ A do
47. BELO CT CTS Cos exocytosis endocytosis 9 36 ETATE SA IcTUUTR LA TAZAI 3 Sa te esicle Endocytosis Requires Re A Ow Fal es amp ee A EAS CX H 7 JANUARY 2005 VOL307 SCIENCE i E A DEB 2 90 pr
48. AMPA 30 ms AMPA Markov AMPA p LGN We T re T J ACSF 10 mM Glu m m E MODEL t 2 4 ms OO Glu Qvo AA d 9 Tu 6562640 Po 0 2 5ms DATA ye wb eam 27 36 EFREFEOSF 88 RA 1 4
49. PPR 0 50 ud 7 PPR 0 22 D 42 7 Open MODEL 217 AMPA 10 Open 0 1 AMPARs 32 Open Control CTZ yDGG DATA Budisantoso TW He 2012 J Neurosci 0 5 0 6 HEA OM WATIE 7 4 AMPA 2 Le 29 36 ETATE SA ICTUUTqR LA TZVAI
50. Ca 3 Ca Ca Ca Ca Ca BC GLC xcitatory Synaptic Transmission in the Inner Retina Paired cordings of Bipolar Cells and Neurons of the Ganglion Cell Layer EE ausus Ca ne SEO aee hum tue n jm ML 7 36 ETATE SA IcTUUTR
51. 4 c2 domain La asco N UA T ET Ke DT rE F de Synaptotagmin Synaptotagmin AEE Miis 12 36 ETATE SA ICTUUTqR LA TAVAI HE6 2 2
52. NMDA Resting membr Ca uds NMDA Mg N AMPFA Na VET NMDA Na Ca NMDA 13 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 Without APV potential Q an zem 420 mV Q Late current without APV 100 pA 150 100 With APV Peak early A current Without APV with APV Peak early A current without APV With APV N Without APV 80 mV
53. 2 Calyx of Held C r t 47htD 2 e gx 20 nm 20 36 ETATE SA IGTUUTqR LA TAVAI W NT J z M v y Ne lM cture replica of _ calyx of 1 Held synapse Nr 4 mM lt E X J P T m gy ieee gt Am gt m a a r wa E face P face
54. eh 3 R T ES H 4 SENDAI JAPAN As O 0 aS 2014 12 11 6 1 8 50 12 10 GB matsui med tohoku acJp http www ims med tohoku acjp matsui 8208 1 XL SERRA dE in Sv ETENA paiaina aii
55. endocytosis SNARE Synaptobrevin VAMP vesicle SNARE vY SNARE SNAP 2S Syntaxin tSNARE SNARE core complex coiled coil zippering Ca
56. NMDA Mg 4 NMDA Ca 4 Ca calmodulin Ca Ef amp U7 calmodulin CamKII DS AMPA AMPA LT Ca calmodulin PKC 15 36 ETATE SA ICTUUTqR LA TAVAI AMPA ZRAZ LTP AMPA AMPA
57. Ca Ce m IDOTI F ca caged Ca Ca Calcium Sensitivity of Glutamate Release in a Calyx Type Terminal caged fiara mmesoma me Ca UV HRI TOL Ca au Ca EMNMEES LIS caged Ca n UV BENI 5c Ca DS Ca Ca 2 Ca 8 36 EAT UE SA IcTUUTR LA TAZAI 4
58. PSD 2 36 ETATE SA ICTUUTL LA TAZAI i E e Jc 5E BB Win p AASTRA AEN eee e gt 3 36 EAT UE S ICTUUTqR LA TAVAI e2 Fo
59. i er Pay P Y vie d F 4 J 2 A ater 2s e2 4 gt _ i gt 4 p Jw e 74 m g 21 36 ETATE SA ICTUUTqR LA TZZAI AMPA 2 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
60. 275 300 35 36 EFRELOS ZR LT WUM4R L AX cM ZAI Jahn R Fasshauer D Principles of Neural Science Molecular machines governing exocytosis of Eric R Kandel James H Schwartz Thomas M synaptic vesicles Jessell Nature 2012 Oct 11 490 7419 201 7 doi McGraw Hill Health Professions Division 10 1038 nature11320 Synapses Malenka RC Nicoll RA W Maxwell Cowan Thomas C S dhof Long term potentiation a decade of progress Charles F Stevens Science 1999 Sep 17 285 5435 1870 4 The Johns Hopkins University Press Morgan SL Teyler TJ http www technologyreview com biomedicine 2 11 Electrical stimuli patterned after the 75 page1 theta rhythm induce multiple forms of LTP J Neurophysiol 2001 Sep 86 3 1289 96 Rizo J Siidhof TC Snares and Munc18 in synaptic vesicle fusion Nat Rev Neurosci 2002 Aug 3 8 641 53 Satzler K Sohl LE 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 1995 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
61. I pA Open AMPARs x Y pS x V V 7 43 9 pA Receptor Kinetic Model MENS NED N 7000 D 0 3 N EFRELYF 22 36 N D N ED
62. LA TZZAI Ca Ca Ca Ca Ca MEME Ca gctotony sypapse Tansmissionin the ner Retin ngs of Bipolar Cells and Ne ia ne of the Gan cdi RO Gud mmm DET Ca A B C Co2 lil ta Ca Co CHET Ca
63. Pr RG stim Mean Variance RC response PPR ae EPSC 1 Pr Analysis 1 0 61 0 39 2 Pr 0 61 40 NxPrxQ N NxPr xPrxQ PPR 0 39 nara nir J f 4613 REDD Outside out AMPA Outide out 7 MI outside out ACSF 10 mM Glu LIT AMPA AMPA 2 4 ms
64. IT WUMqR L A ME ZAI 7 Ca NMDA PECI NMDA Ca
65. RE 33607 TKK Ca SNARE complex 2 1 H 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 Ca
66. TEX 10 pA miniature EPSC te TE miniature BPSC excitatory postsynaptic current EL DO diu scout endocytosis t x EX d We Era vV RR NER p Si aes j Endocytosis
67. 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 19856 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 36 36 EAET UE SA ICTUUTqR LA TZZAI
68. eurons of the ganglion cell layer Journal of Neuroscience 18 4500 4510 ERREF 31 1712 1717 2013 BRAIN and NERVE 65 609 621 2013 H ZRABAEEECCIZRV Clinical Neuroscience 31 24 26 2012 OplusE 396 1085 1090 2008 FE ALP EES 53 435 441 Bollmann JH Sakmann B Borst JG Calcium sensitivity of glutamate release in a calyx type terminal Science 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 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
69. o PPR T PPR N Pr Q 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
70. ope SEM FB FIB SEM 1 2 4 36 EAT UE SA ICTUUTR LA TAVAI SEM 5 serial block face SEM 1 2
71. rcuit aCal circuit 9 RD N ng o LLL CE CCRNERESIESERES Aes R17 2014 1 HIZ Neuron Beppu Matsui Neuron 2014 34 36 EAT UE S4 ICTUUTR LA TZVAI id Beppu K Sasaki T Tanaka KF Yamanaka A IA 2014 Fukazawa Y Shigemoto R Matsui K 2014 Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage Neuron 81 314 320 equal contribution corresponding author H KK T2 2243 2249 2014 AB TF 33 275 280 Budisantoso T Harada H Kamasawa N Fukazawa JA 2013
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