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Rodent Behavioral Learning and Memory Models From Mechanisms of Memory, 2 nd Edition by J. David Sweatt, Ph.D.

Rodent Behavioral Learning and Memory Models0 2 4 6 8 10 0.0 0.1 0.2 0.3 0.4 Time (min) A e 0 2 4 6 8 10 0 100 200 300 400 Time (min) B) 0 2 4 6 8 10 0 10 20 30 Time (min) C y Open

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Page 1: Rodent Behavioral Learning and Memory Models0 2 4 6 8 10 0.0 0.1 0.2 0.3 0.4 Time (min) A e 0 2 4 6 8 10 0 100 200 300 400 Time (min) B) 0 2 4 6 8 10 0 10 20 30 Time (min) C y Open

Rodent Behavioral Learning

and Memory Models

From Mechanisms of Memory, 2nd

Edition by J. David Sweatt, Ph.D.

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Hippocampal Pyramidal Neuron

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“of Mice and Rats”

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Figure 1

Open Field Apparatus

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0 2 4 6 8 100.0

0.1

0.2

0.3

0.4

Time (min)C

en

ter/

tota

l dis

tanc

e

A

0 2 4 6 8 100

100

200

300

400

Time (min)

To

tal d

ista

nce

(cm

)

B

0 2 4 6 8 100

10

20

30

Time (min)

Ve

rtic

al a

ctiv

ity

C

Open Field Behavior

Center/Total Distance

Total Distance Vertical Activity

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Figure 3

Elevated Plus Maze

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Figure 4

Roto Rod

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0 1 2 30

50

100

150

Trial

Tim

e (

se

c)

Figure 5

Rotating Rod Behavior

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0

500

1000

1500

2000

Acou

stic

sta

rtle

reflex

to120

dB

nois

e

74 78 82 86 900

25

50

75

dB

% I

nhib

itio

n

A B

Figure 6

Acoustic Startle and Prepulse

Inhibition

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Hot Plate Test

0

10

20

+/+ n=26

-/- n=20

Hin

d P

aw L

ick

Late

ncy

(s)

Shock Threshold

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

-/- n=6

+/+ n=6

Flinching Jumping Vocalizing

Stim

ulu

s In

tensity

(m

A)

Figure 7

Nociception Behavior

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Figure 8

Visual Cliff

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Ivan Pavlovwith his canine subjects

Image courtesy of Johns Hopkins Medical Institute

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Pavlovian Associative Conditioning

Conditioned

Stimulus

Unconditioned

Stimulus

Conditioned

Stimulus

Unconditioned

Response

Conditioned

Response

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Time

Time

CS

CS

US

US

Delay Conditioning

Trace Conditioning

Categories of Associative Conditioning

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Figure 9

Fear Conditioning Chamber

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TRAINING

CONTEXTUAL TEST CUED TEST

•Animal is placed in novel context

•Hears a tone

•Receives foot shock

•Animal is returned to same context

•Test for freezing behavior

•Animal is placed in modified context

•Hears a tone

•Test for freezing behavior

Fear Conditioning

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Train

What’s that

noise?

Fear Conditioning Paradigm

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Train

Fear Conditioning Paradigm

Yow..!!!

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Train

What’s

going on?

Fear Conditioning Paradigm

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Test

Help!

Train

What’s

going on?

Fear Conditioning Paradigm

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Test

Help!

Train

What’s

going on?

Help!

Fear Conditioning Paradigm

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Page 24: Rodent Behavioral Learning and Memory Models0 2 4 6 8 10 0.0 0.1 0.2 0.3 0.4 Time (min) A e 0 2 4 6 8 10 0 100 200 300 400 Time (min) B) 0 2 4 6 8 10 0 10 20 30 Time (min) C y Open

TRAINING

CONTEXTUAL TEST CUED TEST

•Animal is placed in novel context

•Hears a tone

•Receives foot shock

•Animal is returned to same context

•Test for freezing behavior

•Animal is placed in modified context

•Hears a tone

•Test for freezing behavior

Fear Conditioning

Page 25: Rodent Behavioral Learning and Memory Models0 2 4 6 8 10 0.0 0.1 0.2 0.3 0.4 Time (min) A e 0 2 4 6 8 10 0 100 200 300 400 Time (min) B) 0 2 4 6 8 10 0 10 20 30 Time (min) C y Open

TRAINING

CONTEXTUAL

TEST

CUED TEST

Cue-plus-contextual

Fear Conditioning

A.

TRAININGCONTEXTUAL

TEST

Context Alone Conditioning

Context Discrimination

TRAINING

TEST

Context 1

Context 2

Context 1

B.

C.

Variations of Fear Conditioning

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Fear Conditioning in Angelman

Syndrome Mice

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Control Experiments for

Fear Conditioning

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“Control” Experiments

Performance:

Open Field Activity

Coordination

Perception:

Nociception

Hearing

Vision

Anxiety

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Test

Oh

No!

Freezing Behavior

Train

!@#$

Context + Shock

Latent Inhibition

Test

---

Freezing Behavior

Train

!@#$

Shock

Pre-exposure

---

Latent Inhibition

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Contextual Fear Conditioning

Context + Shock Latent Inhibition0

25

50

75

100

Treatment

Fre

ezin

g B

eh

avio

r(P

erc

en

t o

f T

ime

)

**

Saline 100 mg/kg 300 mg/kg0

25

50

75

100***

MK-801 Treatment

Fre

ezin

g B

eh

avio

r(P

erc

en

t o

f T

ime

)

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Figure 25

Memory Reconsolidation

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Passive Avoidance Paradigm

Step-Through

Passive Avoidance

Step-Down

Passive Avoidance

Train

Test:

measure time to step through

Train

Test:

measure time to step down

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Passive Avoidance

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Active Avoidance Paradigm

Shuttle Box

Active Avoidance

Train Test:Can the animal avoid the shock?

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Corneal Air Puff

Elicits Eyeblink Response

Corneal Air Puff

Given with Tone

Tone Given Alone

Elicits Eyeblink Response

Eye-Blink Conditioning in Rabbits

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“Higher-order” Learning

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Start

Finish

Lashley Maze4 Arm Radial

(Plus) Maze

“Y” Maze“T” MazeTriangle Maze

8 Arm Radial

Maze

Types of Rodent Mazes

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Spatial Learning

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The Morris Water Maze

Camera

Distal Visual

Cues

Platform

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SL327 Impairs Performance in the

Morris Water Maze

0

10

20

30

40

50

60

1 2 3 4 5 6 7 8 9 10 11 12

Control

SL327

Esc

ap

e L

ate

ncy

(sec

)

Training Block(4 trials each)

Hidden Platform

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Morris Water Maze

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No Effect of SL327 in the Visible Platform

Version of the Morris Water Maze

0

10

20

30

40

50

60

1 2 3 4 5 6

ControlSL327

Esc

ap

e L

ate

ncy

(sec

)

Training Block(4 trials each)

Visible Platform

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Morris Water Maze

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The ERK/MAPK Cascade Is Required

For Spatial Learning

Right Trained

Opposite Left

0.0

1.0

2.0

3.0

4.0

5.0

Control 30 mg/kg

SL327

Pla

tfo

rm C

ross

ings ***

0

10

20

30

40

50

60

Control 30 mg/kg

SL327

Qu

ad

ran

t S

earc

h T

ime

(% o

f to

tal

tim

e) ***

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Vehicle30 mg/kg

SL327

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Right Trained

Opposite Left

ERK Is Not Required for Maintenance

of Spatial Memories

0.0

1.0

2.0

3.0

4.0

5.0

Control (1-5)

SL327 (6)

SL327 (1-5)

Control (6)

Pla

tfo

rm C

ross

ing

s ***

0

10

20

30

40

50

60

Qu

ad

ran

t S

earc

h T

ime

(% o

f to

tal

tim

e) **

Control (1-5)

SL327 (6)

SL327 (1-5)

Control (6)

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Joel Selcher and Paige Adams

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The Barnes Maze

Spatial

Cues

Escape

Chamber

Search strategy A

Search strategy B

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“Higher-order” Learning

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Figure 15

Bar Press Operant and/ or Conditioned Place Preference

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Novel Object Recognition

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Figure 24

Novel Object Recognition

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Hermissenda

Image courtesy of Mike Johnson

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Lifelong Single-trial Learning

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NEOPHOBIA TASTE AVERSION

DAY 1

DAY 2

10’

Measure increased consumption

as index of long-term memory

of novel taste

10’

DAY 1

DAY 2

10’

Measure decreased consumption

as index of long-term memory

of novel taste

10’

?

LiCl

Taste Learning

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0.0

0.2

0.4

0.6

0.8

1.0

LiCl NaClgra

ms b

lueberr

y b

ar

Conditioned Taste Aversion

DAY 1

DAY 2

1st Exposure to Food Item

2nd Exposure to Food Item

Injection of LiCl or NaCl

Grams Ingested on 2nd Exposure(LiCl treated group compared to NaCl treated

control)

A B

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Neophobia

DAY 1

DAY 2

1st Exposure to Food Item

A

Grams Ingested(1st exposure compared to second exposure)

B

0.0

0.2

0.4

0.6

0.8

1st intake 2nd intakegra

ms b

lueberr

y b

ar

2nd Exposure to Food Item

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NTS

Amygdala

Insular cortex

NTS

Amygdala

Insular cortex

gustatory

visceroceptive

Figure courtesy of Michael Swank

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Imprinting – Konrad Lorenz

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Test Name Measurement Index Of:

Open Field Analysis Distance Moved Over Time Activity

Elevated Plus Maze Time Spent in Open Arms Anxiety

Rotating-rod Time to Fall Off Coordination and Motor Learning

Acoustic Startle Force of Jump Hearing

Pre-pulse Inhibition Suppression of Startle Sensorimotor Gating

Hot Plate Time to Lick Paw Nociception

Hargreave’s Apparatus Time to Lift Paw Nociception

Light-Dark Exploration Time in Lit Chamber Vision

Visual Cliff Suppression of Movement Vision

Fear Conditioning: Cued Freezing or Startle Auditory Associative Learning

Fear Conditioning: Contextual Freezing or Startle Spatial Associative Learning

Passive Avoidance Time Spent in Lit Chamber Spatial Associative Learning

Active Avoidance Time Spent in Cued Chamber Operant Conditioning

Lever Press Number of Bar Presses Operant Conditioning

Conditioned Place Preference Time Spent in One Chamber Operant Conditioning

Eye-blink Conditioning Blink in Response to Cue Associative Conditioning

Simple Maze Learning Errors or Time to Completion Spatial Learning, Working Memory

Morris Water Maze Quadrant Time, Platform Crossings Spatial Memory

Barnes Maze Errors Spatial Memory

Conditioned Taste Aversion Food or Taste Avoidance Taste Learning

Novel Taste Learning Attenuation of Neophobia Taste Learning

Novel Object Recognition Time Spent with Object Recognition Memory

Behavioral TestsCommonly Used in Rodents