Mechanisms of Memory


  • J. David Sweatt, McKnight Brain Institute, Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

This fully revised 2e provides the only unified synthesis of available information concerning the mechanisms of higher-order memory formation. It spans the range from learning theory, to human and animal behavioral learning models, to cellular physiology and biochemistry. It is unique in its incorporation of chapters on memory disorders, tying in these clinically important syndromes with the basic science of synaptic plasticity and memory mechanisms. It also covers cutting-edge approaches such as the use of genetically engineered animals in studies of memory and memory diseases. Written in an engaging and easily readable style and extensively illustrated with many new, full-color figures to help explain key concepts, this book demystifies the complexities of memory and deepens the reader’s understanding.
View full description


Senior undergraduates and graduate students studying memory, as well as those interested in the medical professions and in translational aspects of basic memory research.


Book information

  • Published: November 2009
  • ISBN: 978-0-12-374951-2

Table of Contents

Foreword to First Edition

Preface to First Edition

Preface to Second Edition


1. Introduction: The Basics of Psychological Learning and Memory Theory

I. Introduction

A. Categories of Learning and Memory

B. Memory Exhibits Long-Term and Short-Term Forms

II . Short-Term Memory

A. Sensory Memory and Short-Term Storage

B. Working Memory

C. The Prefrontal Cortex and Working Memory

D. Reverberating Circuit Mechanisms Contrast with Molecular Storage Mechanisms for Long- Term Memory

III. Unconscious Learning

A. Simple Forms of Learning

B. Unconscious Learning and Unconscious Recall

C. Unconscious Learning and Subject to Conscious Recall

D. Operant Conditioning

E. Currently Popular Associative Learning Paradigms

IV . Conscious Learning - Subject to Conscious and Unconscious Recall

A. Declarative Learning

B. Spatial Learning

V . Summary

Further Reading

Journal Club Articles


2. Studies of Human Learning and Memory

I. Introduction - Historical Precedents with Studies of Human Subjects

A. Amnesias

B. Memory Consolidation

II . The Hippocampus in Human Declarative, Episodic, and Spatial Memory

A. Anatomy of the Hippocampal Formation

B. Lesion Studies in Human Memory Formation

C. Imaging Studies

III . Motor Learning

A. Anatomy

B. Habits

C. Stereotyped Movements

D. Sequence Learning

IV . Prodigious Memory

A. Mnemonists

B. Savant Syndrome

C. You are a Prodigy

V. Summary

Further Reading

Journal Club Articles


3. Non-Associative Learning and Memory

I. Introduction - The Rapid Turnover of Biomolecules

II. Short-Term, Long-Term, and Ultralong-Term Forms of Learning

III. Use of Invertebrate Preparations to Study Simple Forms of Learning

A. The Cellular Basis of Synaptic Facilitation 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. Attributes of Chemical Reactions Mediating Memory

VIII. Sensitization in Mammals

IX. Summary - A General Biochemical Model for Memory

Further Reading

Journal Club Articles


4. Rodent Behavioral Learning and Memory Models

I. Introduction

II. Behavioral Assessments in Rodents

A. Assessing General Activity and Sensory Perception

B. Fear Conditioning

C. Avoidance Conditioning

D. Eye-Blink Conditioning

E. Simple Maze Learning

F. Spatial Learning

G. Taste Learning

H. Novel Object Recognition

I. Studying Memory Reconsolidation Using a Fear Conditioning Protocol

III . Modern Experimental Uses of Rodent Behavioral Models

A. The Four Basic Types of Experiments

B. Use of Behavioral Paradigms in Block and Measure Experiments

IV . Summary

Further Reading

Journal Club Articles


5. Associative Learning and Unlearning

I. Introduction

A. Classical Associative Conditioning

II. Fear Conditioning and the Amygdala

A. Long-Term Potentiation in Cued Fear Conditioning

III. Eye-Blink Conditioning and the Cerebellum

IV. Positive Reinforcement Learning

A. Reward and Human Psychopathology

B. Positive Reinforcement Learning

C. Operant Conditioning of Positive Reinforcement

V. Memory Suppression - Forgetting Versus Extinction, and Latent Inhibition

VI. Summary

Further Reading

Journal Club Articles


6. Hippocampal Function in Cognition

I. Introduction

II. Studying the Hippocampus

A. Hippocampal Anatomy

III. Hippocampal Function in Cognition

A. Space

B. Timing

C. Multimodal Associations - The Hippocampus as a Generalized Association Machine and Multimodal Sensory Integrator

D. The Hippocampus is also Required for Memory Consolidation

IV. Summary

Further Reading

Journal Club Articles


7. Long-Term Potentiation - A Candidate Cellular Mechanism for Information Storage in the Central Nervous System

I. Hebb’s Postulate

II. A Breakthrough Discovery - Long-Term Potentiation in the Hippocampus

A. The Hippocampal Circuit and Measuring Synaptic Transmission in the Hippocampal Slice

B. Long-Term Potentiation of Synaptic Responses

C. Short-Term Plasticity - Paired-Pulse Facilitation and Post-Tetanic Potentiation

III. NMDA Receptor-Dependence of Long-Term Potentiation

A. Pairing Long-Term Potentiation

B. Dendritic Action Potentials

IV. NMDA Receptor-Independent Long-Term Potentiation

A. 200 Hz Long-Term Potentiation

B. Tetra-Ethyl Ammonium Long-Term Potentiation

C. Mossy Fiber Long-Term Potentiation in Area CA3

V . A Role for Calcium Infl ux in NMDA Receptor- Dependent Long-Term Potentiation

VI . Pre-Synaptic Versus Post-Synaptic Mechanisms

VII. Long-Term Potentiation can Include an Increased Action Potential Firing Component

VIII. Long-Term Potentiation can be Divided into Phases

A. Early-Long-Term Potentiation and Late-Long- Term Potentiation - Types Versus Phases

IX. Modulation of Long-Term Potentiation Induction

X. Depotentiation and Long-Term Depression

XI. A Role for Long-Term Potentiation in Hippocampal Information Processing, Hippocampus-Dependent Timing, and Consolidation of Long-Term Memory

A. Long-Term Potentiation in Hippocampal Information Processing

B. Timing-Dependent Information Storage in the Hippocampus

C. Consolidation - Storage of Information within the Hippocampus for Down-Loading to the Cortex

D. A Model for Long-Term Potentiation in Consolidation of Long-Term Memory

XII. Summary

Further Reading

Journal Club Articles


8. The NMDA Receptor

I. Introduction

A.Structure of the NMDA Receptor

II. NMDA Receptor Regulatory Component 1 - Mechanisms Upstream of the NMDA Receptor that Directly Regulate NMDA Receptor Function

A. Kinase Regulation of the NMDA Receptor

B. Redox Regulation of the NMDA Receptor 198

C. Polyamine Regulation of the NMDA Receptor

III. NMDA Receptor Regulatory Component 2 - Mechanisms Upstream of the NMDA Receptor that Control Membrane Depolarization

A. Dendritic Potassium Channels - A-type Currents

B. Voltage-Dependent Sodium Channels

C. AMPA Receptor Function

D. 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

A. Cell Adhesion Molecules and the Actin Matrix

B. Pre-Synaptic Processes

C. Anchoring and Interacting Proteins of the Post- Synaptic Compartment - Post-Synaptic Density Proteins

D. AMPA Receptors 204

E. CaMKII - the Calcium/Calmodulin-Dependent Protein Kinase II

V. Summary

Further Reading

Journal Club Articles


9. Biochemical Mechanisms for Information Storage at the Cellular Level

I. Targets of the Calcium Trigger


B. Two Additional Targets of CaM - Adenylyl Cyclase and Nitric Oxide Synthase

C. Another Major Target of Calcium - PKC

D. Section Summary - Mechanisms for Generating Persisting Signals in Long-Term Potentiation and Memory

II. Targets of the Persisting Signals

A. AMPA Receptors in E-LTP

B. Direct Phosphorylation of the AMPA Receptor

C. Regulation of Steady-State Levels of AMPA Receptors

D. Silent Synapses

E. Pre-Synaptic Changes - Increased Release

F. Post-Synaptic Changes in Excitability?

III. Dendritic Protein Synthesis

IV. An Overview of the Role of Protein Synthesis in Memory

V. Summary

Further Reading

Journal Club Articles


10. Molecular Genetic Mechanisms for Long-Term Information Storage at the Cellular Level

I. Introduction 237

II. Altered Gene Expression in Late-Long-Term Potentiation and Long-Term Memory

III. Signaling Mechanisms

A. A Core Signal Transduction Cascade Linking Calcium to the Transcription Factor CREB

B. Modulatory Influences that Impinge on this Cascade

C. Additional Transcription Factors besides CREB that are Involved in Memory Formation

D. Gene Targets in Late-Long-Term Potentiation

E. mRNA Targeting and Transport

F. Effects of the Gene Products on Synaptic Structure

IV. Experience-Dependent Epigenetic Modifi cations in the Central Nervous System

A. What is Epigenetics?

B. What are Epigenetic Marks and What do they do?

C. Epigenetic Tagging of Histones

D. Signaling Systems that Control Histone Modifications

E. Epigenetic Mechanisms in Learning and Memory

F. Environmental Enrichment and Recovery of Lost Memories

G. Section Summary

V. Neurogenesis in the Adult Central Nervous System

VI. Summary

Further Reading

Journal Club Articles


11. Inherited Disorders of Human Memory - Mental Retardation Syndromes

I. Neurofi bromatosis, Coffi n-Lowry Syndrome, and the ras/ERK Cascade

II. Angelman Syndrome

III. Fragile X Syndromes

A. Fragile X Mental Retardation Syndrome Type 1

B. Fragile X Mental Retardation Type 2

IV. Summary

Further Reading

Journal Club Articles


12. Aging-Related Memory Disorders - Alzheimer’s Disease

I. Aging-Related Memory Decline

A. Mild Cognitive Impairment

B. Age-Related Dementias

II . What is Alzheimer’s Disease?

A. Stages of Alzheimer’s Disease

B. Pathological Hallmarks of Alzheimer’s Disease

C. A β 42 as the Cause of Alzheimer’s Disease

III. Genes - Familial and Late-Onset Alzheimer’s Disease

A. APP Mutations

B. Presenilin Mutations

C. ApoE4 Alleles in Alzheimer’s Disease

IV. Apolipoprotein E in the Nervous System

V. Mouse Models for Alzheimer’s Disease

A. The Tg2576 Mouse

VI. Summary

Further Reading

Journal Club Articles



I. Introduction

II. Introduction to Hypothesis Testing

A. Theories

B. Models

C. Hypotheses

III. The Four Basic Types of Experiments

IV. An Example of a Hypothesis and How to Test it

A. Some Real-life Examples of Hypothesis Testing

V. Some Additional Terminology of Hypothesis Testing

A. Hypothesis Versus Prediction

B. Accuracy, Precision, and Reproducibility

C. Type I and Type II Errors

VI. Summary