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 0.3 0.2 0.1 0.0 0 2 4 6 8 10 Time (min) Center/Total Distance C B 400 30 Total distance (cm) 300 Vertical activity 20 200 10 100 0 0 0 2 4 6 8 10 0 2 4 6 8 10 Time (min) Time (min) Total Distance Vertical Activity

Elevated Plus Maze Figure 3

Roto Rod Figure 4

Rotating Rod Behavior 150 Time (sec) 100 50 0 0 1 2 3 Trial Figure 5

Acoustic Startle and Prepulse Inhibition 75 2000 Acoustic startle reflex to % Inhibition 50 120 dB noise 1500 1000 25 500 0 0 74 78 82 86 90 dB A B Figure 6

Nociception Behavior Shock Threshold 0.35 Hot Plate Test Stimulus Intensity (mA) -/- n=6 0.30 Hind Paw Lick Latency (s) +/+ n=26 +/+ n=6 -/- n=20 20 0.25 0.20 0.15 10 0.10 0.05 0 0.00 Flinching Jumping Vocalizing Figure 7

Visual Cliff Figure 8

Ivan Pavlov with his canine subjects Image courtesy of Johns Hopkins Medical Institute

Pavlovian Associative Conditioning Conditioned Stimulus Unconditioned Stimulus Unconditioned Response Conditioned Stimulus Conditioned Response

Categories of Associative Conditioning Delay Conditioning US CS Time Trace Conditioning US CS Time

Fear Conditioning Chamber Figure 9

Fear Conditioning TRAINING • Animal is placed in novel context • Hears a tone • Receives foot shock CONTEXTUAL TEST CUED TEST • Animal is returned to same context • Animal is placed in modified context • Test for freezing behavior • Hears a tone • Test for freezing behavior

Fear Conditioning Paradigm Train What’s that noise?

Fear Conditioning Paradigm Train Yow..!!!

Fear Conditioning Paradigm Train What’s going on?

Fear Conditioning Paradigm Test Train Help! What’s going on?

Fear Conditioning Paradigm Test Train Help! What’s going on? Help!

Fear Conditioning TRAINING • Animal is placed in novel context • Hears a tone • Receives foot shock CONTEXTUAL TEST CUED TEST • Animal is returned to same context • Animal is placed in modified context • Test for freezing behavior • Hears a tone • Test for freezing behavior

Variations of Fear Conditioning A. B. Cue-plus-contextual Context Alone Conditioning Fear Conditioning CONTEXTUAL TRAINING TEST CUED TEST C. Context Discrimination TEST TRAINING TRAINING Context 1 CONTEXTUAL TEST Context 2 Context 1

Fear Conditioning in Angelman Syndrome Mice

Control Experiments for Fear Conditioning

“Control” Experiments Performance: Open Field Activity Coordination Perception: Nociception Hearing Vision Anxiety

Latent Inhibition Train Test Oh !@#$ No! Context + Shock Freezing Behavior Train Pre-exposure Test !@#$ --- --- Shock Latent Inhibition Freezing Behavior

Contextual Fear Conditioning 100 100 *** ** Freezing Behavior Freezing Behavior 75 (Percent of Time) 75 (Percent of Time) 50 50 25 25 0 0 100 m g/kg 300 m g/kg Context + Shock Latent Inhibition Saline Treatment MK-801 Treatment

Memory Reconsolidation Figure 25

Passive Avoidance Paradigm Step-Down Step-Through Passive Avoidance Passive Avoidance Train Train Test: Test: measure time to step through measure time to step down

Passive Avoidance

Active Avoidance Paradigm Shuttle Box Active Avoidance Test: Train Can the animal avoid the shock?

Eye-Blink Conditioning in Rabbits Corneal Air Puff Tone Given Alone Corneal Air Puff Given with Tone Elicits Eyeblink Response Elicits Eyeblink Response

“Higher - order” Learning

Types of Rodent Mazes 4 Arm Radial 8 Arm Radial Lashley Maze (Plus) Maze Maze Finish Start “T” Maze “Y” Maze Triangle Maze

Spatial Learning

The Morris Water Maze Camera Distal Visual Cues Platform

SL327 Impairs Performance in the Morris Water Maze Hidden Platform Control 60 SL327 Escape Latency 50 40 (sec) 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 Training Block (4 trials each)

Morris Water Maze

No Effect of SL327 in the Visible Platform Version of the Morris Water Maze Visible Platform 60 Control Escape Latency SL327 50 40 (sec) 30 20 10 0 1 2 3 4 5 6 Training Block (4 trials each)

Morris Water Maze

The ERK/MAPK Cascade Is Required For Spatial Learning Right Trained Opposite Left Quadrant Search Time 60 5.0 *** Platform Crossings *** 50 (% of total time) 4.0 40 3.0 30 2.0 20 1.0 10 0 0.0 Control 30 mg/kg Control 30 mg/kg SL327 SL327

30 mg/kg Vehicle SL327

ERK Is Not Required for Maintenance of Spatial Memories Trained Right Opposite Left 5.0 Quadrant Search Time 60 *** Platform Crossings ** 50 (% of total time) 4.0 40 3.0 30 2.0 20 1.0 10 0 0.0 Control (1-5) SL327 (1-5) Control (1-5) SL327 (1-5) Control (6) Control (6) SL327 (6) SL327 (6)

Joel Selcher and Paige Adams

The Barnes Maze Escape Chamber Spatial Cues Search strategy A Search strategy B

“Higher - order” Learning

Bar Press Operant and/ or Conditioned Place Preference Figure 15

Novel Object Recognition

Novel Object Recognition Figure 24

Hermissenda Image courtesy of Mike Johnson

Lifelong Single-trial Learning

Taste Learning NEOPHOBIA TASTE AVERSION ? 10’ DAY 1 10’ DAY 1 LiCl 10’ 10’ DAY 2 DAY 2 Measure increased consumption Measure decreased consumption as index of long-term memory as index of long-term memory of novel taste of novel taste

Conditioned Taste Aversion A B DAY 1 1.0 1 st Exposure to Food Item 0.8 grams blueberry bar 0.6 0.4 Injection of LiCl or NaCl 0.2 0.0 DAY 2 LiCl NaCl Grams Ingested on 2 nd Exposure (LiCl treated group compared to NaCl treated control) 2 nd Exposure to Food Item

Neophobia A B DAY 1 0.8 grams blueberry bar 0.6 1 st Exposure to Food Item 0.4 DAY 2 0.2 0.0 1st intake 2nd intake Grams Ingested 2 nd Exposure to Food Item (1 st exposure compared to second exposure)

gustatory visceroceptive NTS NTS Amygdala Amygdala Insular cortex Insular cortex Figure courtesy of Michael Swank

Imprinting – Konrad Lorenz

Behavioral Tests Commonly Used in Rodents 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