Mechanisms of Memory, 2nd Edition

Mechanisms of Memory, 2nd Edition,J. David Sweatt,ISBN9780123749512


Academic Press




A graduate text reference, this book provides a unique overview of the cellular and molecular mechanisms involved in learning and memory.

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Key Features

  • More than 25% new content, particularly expanding the scope to include new findings in translational research.
  • Unique in its depth of coverage of molecular and cellular mechanisms
  • Extensive cross-referencing to Comprehensive Learning and Memory
  • Discusses clinically relevant memory disorders in the context of modern molecular research and includes numerous practical examples


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.


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

J. David Sweatt

David Sweatt obtained his B.S. in Chemistry from the University of South Alabama before attending Vanderbilt University, where he was awarded a Ph.D. for studies of intracellular signaling mechanisms. He then did a post-doctoral Fellowship at the Columbia University Center for Neurobiology and Behavior, working on memory mechanisms in the laboratory of Nobel laureate Eric Kandel. From 1989 to 2006 he was a member of the Neuroscience faculty at Baylor College of Medicine in Houston, Texas, rising through the ranks there to Professor and Director of the Neuroscience Ph.D. program. Dr. Sweatt’s laboratory studies biochemical mechanisms of learning and memory. In addition, his research program also investigates mechanisms of learning and memory disorders, such as mental retardation and aging-related memory dysfunction. He is currently the Evelyn F. McKnight endowed Chairman of the Department of Neurobiology at UAB Medical School, and the Director of the Evelyn F. McKnight Brain Institute at the University of Alabama in Birmingham. He also is a Professor the Departments of Cell Biology, Genetics, and Psychology at UAB. Dr. Sweatt has won numerous awards and honors, including an Ellison Medical Foundation Senior Scholar Award, and election as a Fellow of the American Association for the Advancement of Science. This year he won (along with Michael Meaney and Catherine Dulac) the Ipsen Foundation International Prize in Neural Plasticity, one of the most prestigious awards in his scientific field. From 1998 until 2002 he attended drawing and painting classes at the Glassell School of Art of the Museum of Fine Arts, Houston. As an artist he explores the use of painting as a medium for expressing topics of interest in contemporary biomedical research. In 2009 he published a textbook, Mechanisms of Memory, which is illustrated with original paintings and describes current models for the molecular and cellular basis of memory formation.

Affiliations and Expertise

McKnight Brain Institute, Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

View additional works by J. David Sweatt

Mechanisms of Memory, 2nd Edition

CHAPTER 1. Introduction - the basics of psychological learning and memory theory.

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

CHAPTER 2. Studies of human learning and memory

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

CHAPTER 3. Non-associative learning and memory

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

CHAPTER 4 Rodent behavioral learning and memory models

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

Performance controls

Short-term memory vs long-term memory

Cued vs contextual

Delay vs trace

IV. Summary

CHAPTER 5. Associative learning and unlearning

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

CHAPTER 6. Hippocampal Function in Cognition

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


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

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 potentials

IV. NMDA receptor-independent LTP

200 Hz LTP


Mossy Fiber LTP in area CA3

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 phases

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

CHAPTER 8. 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

CHAPTER 9. Biochemical mechanisms for information storage at the cellular level.

I. Targets of the Calcium Trigger


B. Adenylyl Cyclase and Nitric Oxide Synthase


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

CHAPTER 10. Molecular genetic mechanisms for long-term information storage at the cellular level.

I. Altered gene expression in memory

II. Signaling mechanisms

1. A core signal transduction cascade linking calcium to the transcription factor CREB

2. Modulatory influences that impinge upon this cascade

3. Additional transcription factors besides CREB that may be involved in long-term memory

4. Gene targets in L-LTP and memory

5. mRNA targeting and transport

6. 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

CHAPTER 11. Inherited disorders of human memory - 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

CHAPTER 12. Aging-related memory disorders - Alzheimer’s Disease.

I. Aging-related memory decline

Mild Cognitive Impairment

II. What is AD?

The stages of AD

Pathological hallmarks of AD

Neurofibrillary tangles

Amyloid plaques

Ab42 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

APPENDIX. The Basics of Experimental Design

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


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