Chapter 3:Non-Associative

Learning and Memory

From Mechanisms of Memory, second editionBy J. David Sweatt, Ph.D.

Cytoskeletal Rearrangement in Synaptic Plasticity

32P

Inco

rpo

rati

on

into

pro

tein

o

r ad

enin

e n

ucl

eoti

des

Time (hrs)

32P added Steady State

Figure 1

Hypothetical Graph of 32P-PO4

C

B

A

Figure 2

AMPA Receptors

Figure 3

Isoelectic Point3 10

Mol

ecul

ar W

eigh

t

High(approx 200 kDa)

Low(approx 5 kDa)

Protein Turnover

Figure 4

Actin Turnover

Figure 5

Aplysia californica

Figure 6

Siphon-gill and tail-siphon

withdrawal reflexes of Aplysia

Figure 7:

C

Short-term Sensitization of the

gill-withdrawal reflex in Aplysia

Figure 8

Circuit Diagrams of the Siphon-gill

Figure 9

Heterosynaptic Facilitation of the Sensorimotor

Figure 10

Molecular events in Aplysia

Figure 11

Mechanisms of long-term memory formation

Substrates

PO4 Substrates

Ubiquitin-mediatedproteolysis

Facilitation ofNeurotransmitter release

PDE

cAMP AMP

cAMP

Shorter Term

Longer Term

Reg. Cat.

Reg. Cat.

Reg. Cat.

Reg. Cat.Reg. Cat.

Reg.Cat.

Cat.

Cat.

Figure 12

PKA

Altered Gene Expression and

Figure 13

Aplysia

Figure 14

Cellular basis of behavior

Figure 15

The Eskin/ Byrne model in Aplysia long-term facilitation

Figure 16

Behavioral SensitizationSpinal Sensitization

Before After

Wit

hd

raw

al

Th

resh

old

pawstimulation

pawstimulation

A.

B. D.

C.Before After

Before After

Before After

Wit

hd

raw

al

Th

resh

old

pawstimulation

pawstimulation

Injury-induced Spinal and Behavioral Sensitization

Figure 17

Anatomical Pain Pathways

Cortex

Spinal cord

Midbrain

Amygdala

Medulla

DRG

Aδ-fiber

C-fiber

Pons

Hypot

hala

mus

PAG

Thalamus

Ascending Pathways

Descending Pathways

Withdrawal Reflex

End-organtissue

no

cicepto

r

termin

als

RVM

Blue Box 1

AdenylylCyclase

αγ

β

GTP GDPATP

cAMP

Substrate

PO4

Reg

Reg

Cat.

Cat.Ion Channels

“Gs” ProteinReceptor

cAMP-DependentProtein Kinase (PKA)

The cAMP System

Receptor

αγ

β

GTP GDP

“Go” Protein

PLC

IP3

DAGCa++

PKC

Substrate

PO4

PIP2

The PLC System

Coupling of Receptors to Intracellular Messengers

Blue Box 2

Potential Signal Transduction routes leading to MAPK Activation in Neurons

GFR

Grb2Rap1

MEK

p42mapk

Raf-1 B-Raf

PKAPKC

PKA

AC

Effectors

SosRas

PO4

ras rasGDP GTP

GTP

GTP Hydrolysis

GAPsGTPase Activating Proteins

e.g. NF1, SynGAP

GEFsGuanine Nucleotide

Exchange Factor Proteins

e.g. SOS, cAMP GEF,

Ca2+/DAG GEF, ras GRF

Inactive Active

++

Blue Box 3

Regulation of RAS

Blue Box 4

Habituation and Synaptic Inhibition

Blue Box 6

Swimming

Contact WithdrawalPreparation for swimming

A

B

C

Escape Swimming in Tritonia