rodent behavioral learning and memory models from mechanisms of memory by j. david sweatt, ph.d
TRANSCRIPT
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Rodent Behavioral Learning and Memory Models
From Mechanisms of Memory by J. David Sweatt, Ph.D.
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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
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0 1 2 3 4 5 6 70
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100
Time (min)
Fre
ezin
g (%
) 0 1 2 3 4 5 60
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50
75
100
Time (min)
Fre
ezi
ng
(%)
0 1 2 3 4 50
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100
Time (min)
Fre
ezi
ng
(%)
Training
Cued
Contextual
Cued-Plus-Contextual Fear Conditioning
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Contextual Fear Conditioning In Rats
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Passive Avoidance Paradigm
Step-Through Passive Avoidance
Step-DownPassive Avoidance
Train
Test: measure time to step through
Train
Test: measure time to step down
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Active Avoidance Paradigm
Shuttle BoxActive Avoidance
Train Test: Can the animal avoid the shock?
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Passive Avoidance
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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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The Morris Water Maze
Camera
Distal Visual Cues
Platform
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1 2 3 4 5 6 7 8 9 10Blocks of 4 trials
Esc
ape
Lat
ency
(se
c)
Hidden Platform
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Blocks of 4 trials
Esc
ape
Lat
ency
(se
c)
Visible Platform
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129/SvImJ
Pla
tfor
m C
ross
ings
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1
Qu
adra
nt
Sea
rch
Tim
e (%
) Opposite
Right Trained
Left
Probe Test
Experimental Results: Morris Water Maze
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VehicleSubject #66Path Length = 1154.2 cm
Subject #57Path Length = 1278.2 cm
30 mg/kg SL327
Path Tracking in the Probe Test
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The Barnes Maze
Spatial Cues
Escape Chamber
Search strategy A
Search strategy B
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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
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Neophobia
DAY 1
DAY 2
1st Exposure to Food Item
A
Grams Ingested(1st exposure compared to second exposure)
B
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1st intake 2nd intakegr
ams
blue
berr
y ba
r
2nd Exposure to Food Item
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• 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
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Contextual conditioning and CRE-mediated Gene Expression in Mice transgenic for CRE-LAC Z
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Hippocampal Protein Kinase Activation in Fear Conditioning
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0 2 4 6 8 100.0
0.1
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Time (min)C
ente
r/to
tal d
ista
nce
A
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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
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0 1 2 30
50
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Trial
Tim
e (s
ec)
Rotating Rod Behavior
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0
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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
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Shock Threshold
0.00
0.05
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0.15
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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
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Corneal Air PuffElicits Eyeblink Response
Corneal Air PuffGiven with Tone
Tone Given AloneElicits Eyeblink Response
Eye-Blink Conditioning in Rabbits
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“of Mice and Rats”