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Hippocampal Pyramidal Neuron
Rodent Behavioral Learning and Memory Models From Mechanisms of - - PowerPoint PPT Presentation
Rodent Behavioral Learning and Memory Models From Mechanisms of - - PowerPoint PPT Presentation
Rodent Behavioral Learning and Memory Models From Mechanisms of Memory, 2 nd Edition by J. David Sweatt, Ph.D. Hippocampal Pyramidal Neuron of Mice and Rats Open Field Apparatus Figure 1 Open Field Behavior A 0.4 Center/total distance
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“of Mice and Rats”
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Figure 1
Open Field Apparatus
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2 4 6 8 10 0.0 0.1 0.2 0.3 0.4 Time (min) Center/total distance
A
2 4 6 8 10 100 200 300 400 Time (min) Total distance (cm)
B
2 4 6 8 10 10 20 30 Time (min) Vertical activity
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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1 2 3 50 100 150 Trial Time (sec)
Figure 5
Rotating Rod Behavior
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500 1000 1500 2000 Acoustic startle reflex to 120 dB noise 74 78 82 86 90 25 50 75 dB % Inhibition
A B
Figure 6
Acoustic Startle and Prepulse Inhibition
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Hot Plate Test
10 20 +/+ n=26
- /- n=20
Hind Paw Lick Latency (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 Stimulus Intensity (mA)
Figure 7
Nociception Behavior
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Figure 8
Visual Cliff
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Ivan Pavlov
with 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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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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TRAINING CONTEXTUAL TEST CUED TEST
Cue-plus-contextual Fear Conditioning
A.
TRAINING CONTEXTUAL 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 Inhibition 25 50 75 100
Treatment Freezing Behavior
(Percent of Time)
**
Saline 100 mg/kg 300 mg/kg 25 50 75 100
***
MK-801 Treatment Freezing Behavior
(Percent of Time)
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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 Maze 4 Arm Radial (Plus) Maze “Y” Maze “T” Maze Triangle 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
10 20 30 40 50 60 1 2 3 4 5 6 7 8 9 10 11 12 Control SL327
Escape Latency
(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
10 20 30 40 50 60 1 2 3 4 5 6
Control SL327
Escape Latency
(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 Platform Crossings ***
10 20 30 40 50 60
Control 30 mg/kg SL327 Quadrant Search Time
(% of total time)
***
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Vehicle 30 mg/kg SL327
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Right Trained Opposite Left
ERK Is Not Required for Maintenance
- f Spatial Memories
0.0 1.0 2.0 3.0 4.0 5.0
Control (1-5) SL327 (6) SL327 (1-5) Control (6)
Platform Crossings ***
10 20 30 40 50 60
Quadrant Search Time
(% of total time)
**
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
- f novel taste
10’ DAY 1 DAY 2 10’ Measure decreased consumption as index of long-term memory
- f novel taste
10’
?
LiCl
Taste Learning
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0.0 0.2 0.4 0.6 0.8 1.0
LiCl NaCl
grams blueberry bar
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 intake
grams blueberry bar
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