Stem Cell Seminar #67 2012 6 7 18:00-19:30

Toshiaki Nakashiba,Ph.D. ( )
Research Scientist
RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning
and Memory, Massachusetts Institute of Technology

"Dentate Gyrus Granule Cells for Pattern Separation and Pattern Completion"

limbic system
hippocampus
in vivo imaging
Cre
DICE-K

Science
2008;319:12601264.
NMDA CA3

TeTX; tetanus
toxin ON/OFF
CA3
CA3 rapid contextual learning and memory
(pattern-based memory recall)
KA-1CAMKII
CAMKII-loxP-STOP-loxP-tTA (Tg2)TetO-TeTX(Tg3-TeTX)TetO-GFP
(Tg3-GFP) 3


limbic system
marginal lobe

mesocortex

thymencephalon

visceral brain

dentate gyrus
hippocampus;)()

CA3
Schaffer

 CA

120
2
(1) CA1 CA3
(2)

Neural Stem Cell

glial fibrillary acidic proteinGFAP
GFAP
GFAP

GFAP NestinPax-6 GFAP

LTP
1973 Bliss

Hz

Long Term PotentiationLTPLTP

CA1 CA3
limbic system

plasticity

long-term
potentiationLTP
Calcium NMDA
LTP NMDA

 place
cell place field
NMDA
Calcium
place field

CA1 LTP

CA3 LTP

mGluR

mG1uR2 mGluR3
CA3

3
Clin Exp Pharmacol Physiol. 1996;23:961-4.
CNS Neurol Disord Drug Targets. 2011;10:433-9.

Limbic system Treatable Psychosis

Treatable Psychosis/dementia
Treatable Psychosis/dementia
2007 NEJM
CT,

MRI T2
Papez
paraneoplastic syndrome
() Yo
Hu Ri paraneoplastic
syndrome

FDG-PET
Treatable Psychosis/dementia
limbic system

CaMKII

CaMKII

(a)(b)
""(c)
phenotype (3)

Daffner KR, Sherman JC, Gonzalez RG,et al. Case records of the Massachusetts
General Hospital. Case 35-2008. A 65-year-old man with confusion and memory loss.
N Engl J Med 359:2155, 2008
Amato AA, Sanelli PC, Anderson MP. Case records of the Massachusetts General
Hospital. Weekly clinicopathological exercises. Case 38-2001. A 51-year-old woman
with lung cancer and neuropsychiatric abnormalities. N Engl J Med 345:1758, 2001
3: Yamasaki N, Maekawa M, Kobayashi K, et al. Alpha-CaMKII deficiency causes
immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders.
Mol Brain. 1:6, 2008.

kinesin superfamily proteinKIF

KIF1A
mRNA
BDNFbrain-derived neurotrophic factor
KIF1A

live cell imaging BDNF

KIF1A
Rab3A
KIF1A
KIF1A

(Neuron 2012 73 743-757.)

broad
selective CA3
potential target neurons 10