Rodent Behavioral Learning and Memory Models From Mechanisms of Memory by J. David Sweatt, Ph.D.
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Transcript of Rodent Behavioral Learning and Memory Models From Mechanisms of Memory by J. David Sweatt, Ph.D.
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”