Rodent Behavioral Learning and Memory Models

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

TRAINING

CONTEXTUALTEST

CUED TEST

Cue-plus-contextual Fear Conditioning

A.

TRAINING CONTEXTUALTEST

Context Alone Conditioning

Context Discrimination

TRAINING

TEST

Context 1

Context 2

Context 1

B.

C.

Variations of Fear Conditioning

0 1 2 3 4 5 6 70

25

50

75

100

Time (min)

Fre

ezin

g (%

) 0 1 2 3 4 5 60

25

50

75

100

Time (min)

Fre

ezi

ng

(%)

0 1 2 3 4 50

25

50

75

100

Time (min)

Fre

ezi

ng

(%)

Training

Cued

Contextual

Cued-Plus-Contextual Fear Conditioning

Contextual Fear Conditioning In Rats

Passive Avoidance Paradigm

Step-Through Passive Avoidance

Step-DownPassive Avoidance

Train

Test: measure time to step through

Train

Test: measure time to step down

Active Avoidance Paradigm

Shuttle BoxActive Avoidance

Train Test: Can the animal avoid the shock?

Passive Avoidance

Start

Finish

Lashley Maze4 Arm Radial (Plus) Maze

“Y” Maze“T” MazeTriangle Maze

8 Arm Radial Maze

Types of Rodent Mazes

The Morris Water Maze

Camera

Distal Visual Cues

Platform

0.0

10.0

20.0

30.0

40.0

50.0

60.0

1 2 3 4 5 6 7 8 9 10Blocks of 4 trials

Esc

ape

Lat

ency

(se

c)

Hidden Platform

0.0

10.0

20.0

30.0

40.0

50.0

60.0

1 2 3 4 5 6

Blocks of 4 trials

Esc

ape

Lat

ency

(se

c)

Visible Platform

0.0

1.0

2.0

3.0

4.0

5.0

129/SvImJ

Pla

tfor

m C

ross

ings

0.0

10.0

20.0

30.0

40.0

50.0

60.0

1

Qu

adra

nt

Sea

rch

Tim

e (%

) Opposite

Right Trained

Left

Probe Test

Experimental Results: Morris Water Maze

VehicleSubject #66Path Length = 1154.2 cm

Subject #57Path Length = 1278.2 cm

30 mg/kg SL327

Path Tracking in the Probe Test

The Barnes Maze

Spatial Cues

Escape Chamber

Search strategy A

Search strategy B

0.0

0.2

0.4

0.6

0.8

1.0

LiCl NaClgr

ams

blue

berr

y ba

r

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

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 intakegr

ams

blue

berr

y ba

r

2nd Exposure to Food Item

• A makes B happen • Measure

• Activating B should cause C • Mimic

• Blocking B should block A causing C • Block

• None (A makes C happen)• Determine

Prediction Experiment

Hypothesis: A→B→C

Four Types of Experiments

Contextual conditioning and CRE-mediated Gene Expression in Mice transgenic for CRE-LAC Z

Hippocampal Protein Kinase Activation in Fear Conditioning

0 2 4 6 8 100.0

0.1

0.2

0.3

0.4

Time (min)C

ente

r/to

tal d

ista

nce

A

0 2 4 6 8 100

100

200

300

400

Time (min)

Tota

l dis

tanc

e (

cm)

B

0 2 4 6 8 100

10

20

30

Time (min)

Ve

rtica

l act

ivity

C

Open Field Behavior

Center/Total Distance

Total Distance Vertical Activity

0 1 2 30

50

100

150

Trial

Tim

e (s

ec)

Rotating Rod Behavior

0

500

1000

1500

2000

Aco

ustic

sta

rtle

refle

x to

120

dB n

oise

74 78 82 86 900

25

50

75

dB

% I

nhib

ition

A B

Acoustic Startle and Pre-Pulse Inhibition Tests

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

ulus

Int

ensi

ty (

mA

)

Hot Plate Test

0

10

20

+/+ n=26-/- n=20

Hin

d P

aw L

ick

Late

ncy

(s)

Nociception Behavior

Corneal Air PuffElicits Eyeblink Response

Corneal Air PuffGiven with Tone

Tone Given AloneElicits Eyeblink Response

Eye-Blink Conditioning in Rabbits

“of Mice and Rats”