神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster...

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Ꮨဃ ܖᴗ䛾㈨ᩱ "Neuroscience“ Editors: Dale Purves et al., Sinauer, (ISBN: 978-0-87893-695-3) Hardcover 5th edition (2012) Companion Website (free) http://sites.sinauer.com/neuroscience5e ᩍ⛉᭩䛻㛵㐃䛧䛯䜰䝙䝯䞊䝅䝵䞁䛺䛹䛜↓ᩱ䛷㜀ぴ䛷䛝䜛 ⏕యሗᏛ◊✲ᐊ䝩䞊䝮䝨䞊䝆䛾୰䛷ㅮ⩏㈨ 䛜㜀ぴ䛷䛝䜛䚹 http://www.bs.s.u- tokyo.ac.jp/~naibunpi/Lecture_Index.html ᇶ♏䛛䜙Ꮫ䜆⚄⤒⏕≀Ꮫ 䛃ᒸ Ⰻ㝯ⴭ 䜸䞊䝮 ᇶ♏ ♏䛛 ᇶ♏ 2012 䛛䜙Ꮫ䜆 䛛䜙Ꮫ 12 12 䜆⚄⤒⏕ Ꮫ䜆 (ISBN978 78 78- ⏕≀ 8 8 -4 - 4 4- 4 4 4 4 - - 274 䛃ᒸ 74 74- 4 4 4 - 21195 Ⰻ㝯 95 95- 㝯ⴭ 5 5 -9) http://ssl.ohmsha.co.jp/cgi- bin/menu.cgi?&ISBN=978-4-274-21195-9 ᪥ᮏㄒ䛾ཧ⪃᭩ 䛂⚄⤒䛸䝅䝘䝥䝇䛾⛉Ꮫ䛃ᬕኵⴭ ㅮㄯ♫䝤 䝹䞊䝞䝑䜽䝇 2015䛂䝙䝳䞊䝻䞁䛸䝸䝉䝥䝍䞊䛃 ➉୰ ᩄⴭ ᇵ㢼 䠔䠕ᖺ∧䠄2006ᖺ⌧ᅾ➨䠏∧䠅 䛂ศᏊ䛛䜙ぢ䛯⬻䛃ᕝ ㏙ⴭ ㅮㄯ♫ 䠕䠐ᖺ 䠄䜲䜸䞁䝏䝱䝛䝹䞉䝺䝉䝥䝍䞊䠅 ⱥㄒ䛾ཧ⪃᭩ From Neuron To Brain. 4 th Ed. Nicholls, J.G., et al., Sinauer, 2001 (ISBN 0-87893- 439-1) 䠄ᩍ⛉᭩䛸䛧䛶ᶆ‽ⓗ䠅 Ion Channels of Excitable Membranes. 3 rd Ed. Hille, B. Sinauer, Associates, 2001 (ISBN 0-87893-321-2)䠄⏕≀≀⌮ⓗ䛺ゎㄝ 䛜ヲ䛧䛔,䜲䜸䞁䝏䝱䝛䝹◊✲䛾䝞䜲䝤䝹ⓗ Ꮡᅾ䠅 ㄞ䜏≀ 䛂⬻䜢ᴟ䜑䜛䛃 ❧ⰼ 㝯ⴭ ᮅ᪥ᗜ 䠌䠍ᖺ ᢸᙜ Ⰻ㝯 ⌮Ꮫ㒊⏕≀Ꮫ⛉䠄≀Ꮫ䠅 ⏕యሗᏛ◊✲ᐊ 䠎㝵䠎䠐䠔ᐊ 㟁ヰ䠖 䠎䠐䠐䠏䠔 e-mail: [email protected] http://www.bs.s.u-tokyo.ac.jp/~naibunpi/䠄ኚ᭦ ὀព䠅 Society for Neuroscience SfN 2011, DC Neuroscience 2010 by the numbers: 31,975 attendees

Transcript of 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster...

Page 1: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

• "Neuroscience“ Editors: Dale Purves et al., Sinauer, (ISBN: 978-0-87893-695-3)Hardcover 5th edition (2012)

• Companion Website (free)http://sites.sinauer.com/neuroscience5e

• http://www.bs.s.u-tokyo.ac.jp/~naibunpi/Lecture_Index.html

•20121212 (ISBN9787878-88-4-44-4444--2747474-444-211959595-55-9)

• http://ssl.ohmsha.co.jp/cgi-bin/menu.cgi?&ISBN=978-4-274-21195-9

•2015

•2006

• From Neuron To Brain. 4th Ed. Nicholls, J.G., et al., Sinauer, 2001 (ISBN 0-87893-439-1)

• Ion Channels of Excitable Membranes. 3rd

Ed. Hille, B. Sinauer, Associates, 2001 (ISBN 0-87893-321-2)

,

••

••• e-mail: [email protected]• http://www.bs.s.u-tokyo.ac.jp/~naibunpi/

••••••••••••••

Society for Neuroscience

SfN 2011, DC

Neuroscience 2010 by the numbers:31,975 attendees

Page 2: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

Society for Neuroscience 2009399thth Annual Meeting, Chicago (29,980 attendees)

2009 SfN Chicago, Poster Sessions

McCormick Place, Chicago Convention Center

Special Lecture, President T. Carew

Lake Michigan

McCormick Place

Society for Neuroscience 2012422ndnd Annual Meeting, New Orleans (28,505 attendees)

2012 SfN New Orleans

Drs. L. Jan & Y.N. Jan Poster Sessions Eric Kandel

Page 3: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

2008.10.09

GFPFP-P-GnRHH medakaTransgenic GFP-GnRH1 neurons Transgenic GFP-GnRH3 neurons

Medaka

•Genome database•Transparent•Spawn daily

Tg gnrh1

Tg gnrh2

Tg gnrh3

Tg gnrh2

Brain

Remove tectum

Electrode

Transgenic GFP-GnRH2 neurons

Whole brain in vitroOkubo et al. (2006)

Kanda et al. (2010)

Pituitary

POA

Spawn da

i GFWhole brain

G RFP

ailydan in vitro

RH2RHo prep

Page 4: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

GFP

WT F0 ( )

F1

MedakaIn vivooo Caaa2+++++

–– –

Inverse pericamCRISPR-Cas9 / TALEN

GFP / -

1

GFP / GFPGFP / --/ -

GFP / -

F0

F1

F2

F2

Kiss1/kiss2

SV40 polyAPcmcl2DsRed

SV40polyA

F2F2

Daily cyclicity in pituitary lh gene expression

lhb mRNA

POAA-A-GGGG RH1 neuron activity y and d lhhh gene POAAA GGGG RH1 neuroRexpression show

on activityy ndandeurow w daily cyclicity

Daily cyclicity in AP firing activity of GnRH1 neurons

Karigo et al., 2012

Spontaneous action potential(AP) firing13:00

16:00

may be related to preovulatory GnRH/LH surge may be related to preovulator DL (spawning) cyclicity

Page 5: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

IP

LH FSH Ca2+

LHβ-IP

FSHβ-IP

50μm

50μm

LH

Ca

FSHCa

Baseline peak 20-80%

Cells from 6 fish

173 147

BBas peak 20 80selineseelinese

[Ca2+]i GnRH

LH

FSH

Page 6: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2013/

Page 7: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

(10/04/2004)

http://nobelprize.org/

200002000

(10/04/2004)200404200004

Page 8: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

200002000

20000020000

Page 9: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

199191199991http://sites.sinauer.com/neuroscience5e/animations04.01.html

2004

Page 10: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

1.

2.

3.

4.

10/09 00:37

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Fig 1. The dividing wall between the cell and the outside world – including other cells – is far from being an impervious shell. On the contrary, it is perforated by various channels. Many of these are specially adapted to one specific ion or molecule and do not permit any other type to pass. Here to the left we see a water channel and to the right an ion channel.

Fig 2. Peter Agre’s experiment with cells containing or lacking aquaporin. The aquaporin is necessary for making the cell absorb water and swell.

Brain•••

2004 Sinauer Associates, Inc.

(Kole, 2011)

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2004 Sinauer Associates, Inc.

(A) – (D)

(G), (H)

(E), (F)

(I)(I)(J) ( ) ( )(K)

(L)

(M) (N) (O)

(P)

2004 Sinauer Associates, Inc.

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A/D D/A

1.5mm

Page 14: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.
Page 15: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.
Page 16: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

Patch pipettes

m

in vitro

ON

Tel.

Cut

OB

rostral

caudal

Cut

OT

••

••

(mV

)(n

A)

2004 Sinauer Associates, Inc.

Page 17: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

-90

-80

-70

-60

-50

-40

-30

-20

-10

0

(mV

)(n

A)

A B

E

C

D

V=Vmax 1- exp(-t/RC)RC=

nA

mV

-0.15 -0.1 -0.05 0 0.05 0.1 015

nA

0mV

-65mV

F

G

+/- 0.05 nA +/- 0.10 nA +/- 0.15 nA

F

Vm

ax/V

V=Vmax 1- exp(-t/ )

2004 Sinauer Associates, Inc.

G

E=0 E=EK

K+K+

A- A-

K+ K+

A- A-

---- +

+

++

K+

1

221 ][

][lnKK

FRTEEEK

K+

K+

Nernst

Page 18: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

K+ =

K+K+ K+

K+

58mV

Nernst

SEsR (8.315joule/deg mol)T 20℃ 293K)F (96,480coul/mol)Goldman-Hodgkin-Kat

oCliNaik

iCloNaok

oCliNaik

iCloNaokm

ClPNaPKPClPNaPKP

ClPNaPKPClPNaPKP

FRTE

][][][][][][log58

][][][][][][ln

10

1

210

1

221 ][

][log303.2][][ln

SS

FZRT

SS

FZRTEEEs

ss

K+ Na+

(mV)

-75+55(-60;Clin=52)

2004 Sinauer Associates, Inc.

(mV

)(m

V)

(mV

)(m

V)

(mV

)

Na+

58mV

(mV

)(m

V)

K+

58mV

2004 Sinauer Associates, Inc.

Page 19: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

20 mTN-GnRH neurons

100 m

m

GnRH-3

A B

Neher & Sakmann, 1991

1~2pA

0pA

ABNa+

Na+

Na+ Na+

Na+

Whole-cellI

I=i1+i2+ in

i2 i1i3

i4

i5

in

in-1

Na+

3 Na+

10 Na+

Na+

-60mV

0mV

1pA

1pA

10pA

100nA~

i

On-cell

i

Page 20: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

Na+ K+

(mV

)

(mV

)

(mV

)

Na+

K+

Na+

(nA

)N

a+

(nA

)

K+

(nA

)K

+

(mA

/cm

2 )

Na+ K+

0

0.5

1

0

0.5

1

2004 Sinauer Associates, Inc.

Page 21: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

Hodgkin, A. & Huxley, A.1963

(Eccles, J.C. )

2004 Sinauer Associates, Inc.

(Vm) Vm (Vm)

(mV

)(m

A/c

m2 )

65mV

65mV

(mA

/cm

2 )(m

V)

2004 Sinauer Associates, Inc.

Page 22: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

(mV

)(m

A/c

m2 )

(mV

)(m

A/c

m2 ) TEA

A

B C

D

0

0.5

1

(mV)

TTX Na

(mA

/cm

2 )

(mV)

Na K

-40

-30

-20

-10

0

10

20

-60 -30 0 25 50 60

Na INa=gNa*(Vm-ENa )

g_Na*(V_m-E_Na )

Na+

(Vm) -60 -30 0 25 50 600 0.15 0.75 1 1 1

(Vm-ENa ) -110 -80 -50 -25 0 10gNa *(Vm-ENa ) 0 -12 -37.5 -25 0 10

0

20

40

60

80

100

120

140

-60 -30 0 25 50 60

K Ik=gK*(Vm-EK )g_K*(V_m-E_K )

K+

(Vm) -60 -30 0 25 50 600 0.15 0.75 1 1 1

(Vm-EK) 0 30 60 85 110 120gK*(Vm-EK ) 0 4.5 45 85 110 120

Page 23: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

(mV

)(m

A/c

m2 )

Na+

(mS/

cm

2 )K

+(m

S/ c

m2 )

2004 Sinauer Associates, Inc.(m

V)

(mSi

emen

s/cm

2 )

(mV

)

Na+ K + 7, 15, 90 mV

Na+

Na+

K+

K+

(mSi

emen

s/cm

2 )

mV

2004 Sinauer Associates, Inc.

Na+

2m: Na+

h: Na+

n: K+

Page 24: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

(mV

)(m

V)

(mm)

(mm)

(mV

)(m

V)

→→

=1/e

2004 Sinauer Associates, Inc.

Na1

Na3

2

Na K45

2004 Sinauer Associates, Inc.

Page 25: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

2004 Sinauer Associates, Inc.

Vx=V0 exp(-x/ )

=

Vx:

V0: length constant,

rm: ri:

ro:

Rm:

Ri

rm=Rm/2 ari=Ri/ a2

=

d=2a d: a:

Page 26: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

cRNA

cRNA

(A) (B)(C) mRNA

K+

K+

(mV

)(

A)

2004 Sinauer Associates, Inc.

Hydropathic index→ hydrophobicity=

Page 27: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

Na+ Channel K+ ChannelNa+

K+

S

Na+

2004 Sinauer Associates, Inc.

ShB

R: ArgK: Lys

(E: Glu)

Page 28: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

2004 Sinauer Associates, Inc.

Page 29: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

2004 Sinauer Associates, Inc.

KThe Structure of the Potassium Channel:

Molecular Basis of K+

Conduction and SelectivityDeclan A. Doyle, Joa˜ o Morais Cabral,

Richard A. Pfuetzner, Anling Kuo, Jacqueline M. Gulbis, Steven L. Cohen, Brian T. Chait,

Roderick MacKinnon* SCIENCE VOL. 280 3 APRIL 1998

Ion conduction pore is conserved among

potassium channelsZhe Lu, Angela M. Klem & Yajamana RamuNATURE |VOL 413 | 25 OCTOBER 2001

Bacterial K channelKcsA

2004 Sinauer Associates, Inc.

Page 30: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

Na

The voltage-sensitive sodium channel is a bell-shaped molecule with several cavitiesChikara Sato*, Yutaka Ueno*, Kiyoshi Asai*, Katsutoshi Takahashi², Masahiko Sato³, Andreas Engelß & Yoshinori FujiyoshiNature 409:1047-1051(2001)

2004 Sinauer Associates, Inc.

Page 31: 神経細胞(ニューロン) の構造naibunpi/Oka/KomabaLecture-1.pdf2009 SfN Chicago, Poster Sessions McCormick Place, Chicago Convention Center Special Lecture, President T.

2004 Sinauer Associates, Inc.