神経細胞（ニューロン） の構造naibunpi/oka/komabalecture-1.pdf2009 sfn chicago, poster...

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• 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)

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Society for Neuroscience

SfN 2011, DC

Neuroscience 2010 by the numbers:31,975 attendees

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

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

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

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

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

(10/04/2004)

http://nobelprize.org/

200002000

(10/04/2004)200404200004

200002000

20000020000

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

2004

1.

2.

3.

4.

10/09 00:37

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)

2004 Sinauer Associates, Inc.

(A) – (D)

(G), (H)

(E), (F)

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

(L)

(M) (N) (O)

(P)

2004 Sinauer Associates, Inc.

A/D D/A

1.5mm

Patch pipettes

m

in vitro

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caudal

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2004 Sinauer Associates, Inc.

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nA

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nA

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

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ax/V

V=Vmax 1- exp(-t/ )

2004 Sinauer Associates, Inc.

G

E=0 E=EK

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+

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2004 Sinauer Associates, Inc.

(mV

)(m

V)

(mV

)(m

V)

(mV

)

Na+

58mV

(mV

)(m

V)

K+

58mV

2004 Sinauer Associates, Inc.

20 mTN-GnRH neurons

100 m

m

GnRH-3

A B

Neher & Sakmann, 1991

1~2pA

0pA

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Na+

Na+ Na+

Na+

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I=i1+i2+ in

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(mV

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/cm

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2004 Sinauer Associates, Inc.

Hodgkin, A. & Huxley, A.1963

(Eccles, J.C. )

2004 Sinauer Associates, Inc.

(Vm) Vm (Vm)

(mV

)(m

A/c

m2 )

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2004 Sinauer Associates, Inc.

(mV

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Na INa=gNa*(Vm-ENa )

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(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

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

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(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

(mV

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2004 Sinauer Associates, Inc.(m

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Na+

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2004 Sinauer Associates, Inc.

Na+

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h: Na+

n: K+

(mV

)(m

V)

(mm)

(mm)

(mV

)(m

V)

→→

=1/e

2004 Sinauer Associates, Inc.

Na1

Na3

2

Na K45

2004 Sinauer Associates, Inc.

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:

cRNA

cRNA

(A) (B)(C) mRNA

K+

K+

(mV

)(

A)

2004 Sinauer Associates, Inc.

Hydropathic index→ hydrophobicity=

Na+ Channel K+ ChannelNa+

K+

S

Na+

2004 Sinauer Associates, Inc.

ShB

R: ArgK: Lys

(E: Glu)

2004 Sinauer Associates, Inc.

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.

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.

2004 Sinauer Associates, Inc.