Biochemical Mechanisms for Long-term Information

Storage at the Cellular Level

From Mechanisms of Memory by J. David Sweatt, Ph.D.

Protein Synthesis Dependence of L-LTP

Kang et al. (2001) Cell 106:771-783.

CREB Binding Protein (CBP)

cAMP Response Element5’-TGACGTCA-3’

TATA Sequence

CREB CREB

Basal Transcription Factor IID (TFIID)

Complex

ser 133 ser 133

RNA Helicase A

RNAPolymerase II

Histone

pKAF

acetylation

TargetGene

PO4 PO4

The CREB/CRE Gene Regulation System

Figure courtesy of Jennifer GatchelBrookhaven National Protein Structure Data Bank, Rendered with Rasmol

Crystal Structure of CREB bound to the CRE

Activity-dependent Regulation of Gene Expression

CRE SRE zif268

C/EBP krox20

AMPARHOMERBDNFNT-3

MKP-1SSAT

Arc

CBP/CREB

CaMKIV + ERK

Elk-1

RSK2

Transcriptional Regulation Pathways

Steward and Worley (2001) PNAS 98:7062-7068.

Activity-dependent Arc Expression and Dendritic Localization

Hypothetical Mechanisms for Activity-dependent changes in Synaptic Structure

Presynaptic

Postsynaptic

IntegrinsIntegrins

Ca++Ca++

actin

Pax

illin

FAK (Focal Adhesion Kinase)

grb2/sos cas/crk src

ERK JNK

α αββrho rac

Dynamiccytoskeletalregulation

Cadherins

Catenins

?

DMPK

MyosinPhosphatase

CytoskeletalMyosin II

-

-

α-actinintalin

vincu

lin α-actinin

Signaling Mechanisms Used by Integrins and Cadherins

Villarreal et al. (2002). Nat. Neurosci. 5:48-52.

L-LTP Decay is an Active Process

Tra

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yeb

link

De

lay

Eye

blin

kM

orr

is W

ate

rma

zeP

ost

tra

inin

g I

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Neurogenesis in the Adult CNS

Gould et al. (1999) Nat. Neurosci. 2:260-265.