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Table of Contents

Mechanisms of Memory

(2nd Edition)

J. David Sweatt, Ph.D.


Introduction – the basics of psychological learning and memory theory

Chapter 1 Painting Title:  Multiple Memory Systems
I.     Introduction
       Categories of learning and memory
       Memory exhibits Long-term and Short-term forms
       Consolidation and Reconsolidation
       Latent Inhibition
II.    Short-term memory
Sensory Memory and Short-term storage
Working Memory
The Prefrontal Cortex and working memory
Reverberating Circuit mechanisms contrast with molecular storage
       mechanisms for long-term memory
III.   Unconscious Learning
Simple forms of learning
Unconscious learning and Unconscious recall
Motor learning
Unconscious learning and subject to conscious recall
Operant conditioning
Popular Associative learning types
Eye-blink conditioning as an example
Trace vs delay conditioning – role of hippocampus
Fear Conditioning
IV.  Conscious learning – higher order cognitive function
Declarative Learning
Spatial Learning
V.   Summary
BLUE BOX 1: Learning in a plant?  “Sensitization” in the Venus’ Flytrap
BLUE BOX 2: Non-graded acquisition of memory:  food aversion and imprinting
BLUE BOX 3: APLYSIA in its natural habitat.
BLUE BOX 4: HERMISSENDA: The good-looking one in the family.
BLUE BOX 5: A rodent model of declarative memory?
Suggested Readings:  13
Journal Club Articles: 3
Cited References:  14


Studies of human learning and memory

Chapter 2 Painting Title: Medium Spiny Neuron
I.    Introduction – historical precedents with studies of human subjects
Memory consolidation
II.   The hippocampus in human declarative, episodic, and spatial memory
Anatomy of the hippocampal formation
The hippocampus in memory consolidation
Human lesion studies
Human imaging studies
The cab-driver study
III.   Motor Learning
Stereotyped movements
Sequence learning
IV.  Prodigious memory
Autistic Savants
You are a prodigy
V.   Summary
BLUE BOX 2– Studies in non-human primate models
BLUE BOX 3- drug addiction and reward
Suggested Readings:  21
Journal Club Articles:  4
Cited References:  22


Non-associative learning and memory

Chapter 3 Painting Title: Cytoskeletal Rearrangement in Synaptic Plasticity
I.     Introduction – the rapid turnover of biomolecules
II.    Short, long, and ultralong-term forms of learning
III.   Use of invertebrate preparations to study simple forms of learning — Sensitization in Aplysia
IV.  Short-term facilitation in Aplysia is mediated by changes in the levels of intracellular second messengers
V.   Long-term facilitation in Aplysia involves altered gene expression and persistent protein kinase activation—a second category of reaction
VI.  Long-term synaptic facilitation in Aplysia involves changes in gene expression and resulting anatomical changes.
VII. Three attributes of chemical reactions mediating memory
Short half-life reactions
Long half-life reactions
Ultralong-term memory: Mnemogenic chemical reactions 
VIII. Human Sensitization
IX.  Summary: A general chemical model for memory
BLUE BOX 1: PKA and PKC signaling in cells
BLUE BOX 2: MAPK signaling
BLUE BOX 3: Regulation of ras by GAPs and GEFs
BLUE BOX 4: Habituation and Synaptic Inhibition
BLUE BOX 5: Forgetting  
BLUE BOX 6: Central Pattern Generators
BLUE BOX 7: Summary: Some Unifying Themes in Memory Research
Suggested Readings:  9
Journal Club Articles:  5
Cited References:  20


Rodent behavioral learning and memory models

Chapter 4 Painting Title: Hippocampal Pyramidal Neuron
I.     Introduction
II.    Behavioral Assessments in Rodents
A.    Activity and sensory perception assessments
Open Field Analysis and Elevated Plus maze performance
Rotating-rod performance–coordination and motor learning
Acoustic Startle and Pre-pulse inhibition
Vision Tests–Light-Dark Exploration and Visual Cliff
B.    Fear conditioning
Cue-plus-contextual fear conditioning
Cued fear conditioning
Contextual Fear Conditioning
C.   Avoidance and operant conditioning
Passive avoidance
Active avoidance – operant conditioning
Lever pressing
Conditioned place preference
 D.   Eye-blink conditioning
 E.   Simple Maze learning
 F.   Spatial learning
Morris Maze
Barnes Maze
 G.  Taste Learning
Conditioned taste aversion
Novel Taste Learning and Neophobia
H.   Novel object recognition
I.     Memory Reconsolidation
III.  Modern experimental usage of rodent behavioral models
A.  A review of the 4 basic kinds of experiments
B.  Measure Experiments
C.  Block Experiments
IV.  Performance controls
Short-term memory vs long-term memory
Cued vs contextual
Delay vs trace
V.   Summary
BLUE BOX 1:  Of Mice and Rats
BLUE BOX 2:  Characterizing a genetically engineered mouse
BLUE BOX 3:  SUMMARY: Behavioral tests commonly used in rodents
Suggested Readings:  11
Journal Club Articles:  4
Cited References:  15


Associative learning and unlearning

Chapter 5 Painting Title: Purkinje Neuron
I.     Introduction
Classical associative conditioning
II.    Fear conditioning and the amygdala
LTP in cued fear conditioning
III.   Eye-blink conditioning and the cerebellum
IV.  Positive reinforcement learning
Reward and human psychopathology
Positive reinforcement learning
Operant conditioning of positive reinforcement
V.   Memory Suppression: Forgetting versus Extinction, Reconsolidation, and Latent Inhibition
VI.  Summary
BLUE BOX 1– Invertebrate models in associative conditioning
BLUE BOX 2– Honeybee PER
BLUC BOX 3 Drosophila odor discrimination
BLUE BOX 4- Hermissenda
BLUE BOX 5– Lymnaea
BLUE BOX 6 Aplysia associative conditioning
BLUE BOX 7- Bird-brains
BLUE BOX 8- Adaptation of the VOR
BLUE BOX 9– Reconsolidation of memories
Suggested Readings: 17
Journal Club Articles: 3
Cited References:  8


Hippocampal Function in Cognition

Chapter 6 Painting Title: Grid Cell
I.     Introduction
       The hippocampus is required for memory consolidation
II.    Studying the hippocampus
The hippocampus serves a role in information processing – space, timing, and relationships
Review of hippocampal anatomy
III.  Hippocampal function in cognition
A.   Space
B.   Timing
Memory for Real Time—Episodic memory, ordering, and the CS-US interval
C.   Multimodal associations—the hippocampus as a generalized association 
       machine and multimodal sensory integrator
IV.  Summary
BLUE BOX 1– Grid Cells in the entorhinal cortex
BLUE BOX 2– Arc and cellular re-activation
BLUE BOX 3– Sleep and memory consolidation.
Suggested Readings:  9
Journal Club Articles:  3
Cited References:  34


Long-term Potentiation: A Candidate Cellular Mechanism for Information Storage in the CNS

Chapter 7 Painting Title: Stratum Pyramidale
I.     Hebb’s Postulate
II.    A breakthrough discovery—LTP in the hippocampus
Synapses in the hippocampus—the hippocampal circuit
The hippocampal slice preparation
Measuring synaptic transmission in the hippocampal slice
Short-term plasticity: PPF and PTP
III.   NMDA receptor-dependence of LTP
Pairing LTP
Dendritic action potential
IV.  NMDA receptor-independent LTP
200 Hz LTP
Mossy Fiber LTP in area CA
V.   A role for calcium influx in NMDA receptor-dependent LTP
VI.  Presynaptic versus postsynaptic mechanisms
VII.   LTP can include an increased AP firing component
VIII.  LTP can be divided into phase
IX.  Modulation of LTP induction
X.   Depotentiation and LTD
XI.  A role for LTP in hippocampal information processing, hippocampus-
dependent timing, and consolidation of long-term memory
XII.  Summary
BLUE BOX 1 – Types of receptors and potential sites of plasticity
BLUE BOX 2 – Global cell-wide changes as mechanisms contributing to memory
BLUE BOX 3 – Monitoring baseline synaptic transmission
BLUE BOX 4 – Recording from individual neurons
BLUE BOX 5 – A need for postsynaptic protein kinase activity in LTP induction
BLUE BOX 6 – Temporal integration in LTP induction
BLUE BOX 7 – Spine anatomy and biochemical compartmentalization
BLUE BOX 8 – Saturating LTP blocks memory formation
BLUE BOX 9: Hippocampal LTP happens when an animal learns
Suggested Readings:  16
Journal Club Articles:  5
Cited References:   80


The NMDA Receptor

Chapter 8 Painting Title: The NMDA Receptor
I.     Introduction
       Structure of the NMDA receptor
II.    NMDA receptor regulatory component 1: Mechanisms upstream of the NMDA receptor that directly regulate NMDA receptor function.
       Kinase regulation of the NMDA Receptor
Redox regulation of the NMDA Receptor
Polyamine regulation of the NMDA receptor
III.  NMDA receptor regulatory component : Mechanisms upstream of the NMDA receptor that control membrane depolarization.
Dendritic Potassium Channels – A-type Currents
Voltage-dependent sodium channels
AMPA receptor function
GABA receptors
IV.  NMDA receptor regulatory component 3: The components of the synaptic infrastructure that are necessary for the NMDA receptor and the synaptic signal transduction machinery to function normally.
Cell Adhesion Molecules and the Actin Matrix
Presynaptic Processes
C. Anchoring and Interacting Proteins of the Postsynaptic Compartment:  the Post-Synaptic Density
AMPA Receptors
V.   Summary
Suggested Readings:  15
Journal Club Articles:  5
Cited References:  53


Biochemical mechanisms for information storage at the cellular level

Chapter 9 Painting Title: Dendritic Spine
I.    Targets of the Calcium Trigger
      A.  CaMKIIAdenylyl
      B.  Cyclase and Nitric Oxide Synthase
      C.  PKC
II.   Targets of the Persisting Signals
Receptor phosphorylation
Receptor insertion
Silent Synapses
Presynaptic changes
Changes in excitability
III.   Protein synthesis in LTP and Memory
Local protein synthesis
Altered protein synthesis as a trigger for memory
IV.  Summary
BLUE BOX 1 – CaMKII as a temporal integrator
BLUE BOX 2 – Oxidation of PKC
BLUE BOX 3 – Another potential target of calcium—Phospoholipases
BLUE BOX 4 –  Synaptic tagging and the E-LTP/L-LTP transition
Suggested Readings:  14
Journal Club Articles:  4
Cited References:  74


Molecular genetic mechanisms for long-term information storage at the cellular level

Chapter 10 Painting Title: Chromatin Remodeling in Memory Formation
I.     Altered gene expression in memory
II.    Signaling mechanisms
A.  A core signal transduction cascade linking calcium to the transcription factor CREB
B.  Modulatory influences that impinge upon this cascade
C.  Additional transcription factors besides CREB that may be involved in long-term memory
D.  Gene targets in L-LTP and memory
E.  mRNA targeting and transport
F.  Effects of the gene products on synaptic structure
III.   Epigenetic mechanisms in memory formation
IV.   Neurogenesis in the adult CNS
V.   Summary – Altered genes and altered circuits
BLUE BOX 1: Neural development and differentiation
BLUE BOX 2: Mother’s Day – every day of your life
Suggested Readings:  20
Journal Club Articles:  5
Cited References:   138


Inherited disorders of human memory – mental retardation syndromes

Chapter 11 Painting Title: Mental Retardation Syndromes
I.     Neurofibromatosis, Coffin-Lowry Syndrome, and the ras/ERK cascade
II.    Angelman Syndrome
III.   Fragile X Syndromes
Fragile X Mental Retardation Syndrome Type 1
Fragile X Mental Retardation Type 2
IV.  Summary
BLUE BOX 1 – Rubinstein-Taybi Syndrome
BLUE BOX 2 – Rett Syndrome
BLUE BOX 3 – Williams Syndrome
BLUE BOX 4 – Non-syndromic X-linked Mental Retardation – Rho GEF6 and PAK3 mutations
BLUE BOX 5 – Down’s Syndrome
BLUE BOX 6 – Nurture vs Nature
Suggested Readings:  15
Journal Club Articles:  4
Cited References:  45


Aging-related memory disorders – Alzheimer’s Disease

Chapter 12 Painting Title: Amyloid Plaques and Neurofibrillary Tangles
I.     Aging-related memory decline
       Mild Cognitive Impairment
II.    What is AD?
The stages of AD
Pathological hallmarks of AD
Neurofibrillary tangles
Amyloid plaques
Aβ42 as the cause of AD
III.   Genes—Familial and late onset AD
APP mutations
Presenilin mutiations
ApoE4 alleles in AD
IV.  Apolipoprotein E in the nervous system
V.   Mouse models for AD
APP mutant mice
Presenilin mutant mice
The 3xTg-AD triple-mutant mouse
Tg2576 mouse
VI.  Summary
BLUE BOX 1 – Diagnosing AD
BLUE BOX 2 – The Cholinergic Hypothesis of AD and Current Pharmacotherapies
BLUE BOX 3 – Aβ peptide immunization as a potential therapy for AD.
BLUE BOX 4 – The Nun study
Suggested Readings:  14
Journal Club Articles:  4
Cited References:  114


The Basics of Experimental Design

Appendix Painting Title: Growth Cone
I.      Introduction
II.     Hypothesis testing – Theories, models, hypotheses, predictions, experiments
III.   The 4 basic types of experiments  
IV.   An Example of a Hypothesis and How to Test It
The Car
All the predictions can test true but the hypothesis still be wrong
Control experiments
Some Real-life Examples of Hypothesis Testing
Testing a Thought Hypothesis
The beta-adrenergic receptor hypothesis
V.  The Terminology of Hypothesis Testing
Hypothesis versus Prediction
Accuracy, Precision and Reproducibility
Type I and Type II Errors
VI.  Summary
BLUE BOX 1 – Computer and Mathematical Modeling
BLUE BOX 2 – Legality, Ethicality, and Morality
BLUE BOX 3 – What the Heck is a Null Hypothesis?
BLUE BOX 4 – Random Error and Systematic Error
BLUE BOX 5 – Human Clinical Studies
Cited References:  12




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