Mechanisms of Memory: Sweatt: 9780126789577: Book: Medical: eCampus.com

This book stands as the first unified overview of the cellular and molecular mechanisms underlying higher-order learning and memory. It integrates modern discoveries concerning learning and memory disorders such as mental retardation syndromes and Alzheimer's Disease, while also emphasizing the results gained from the cutting-edge research methodologies of genetic engineering, complex behavioral characterization, proteomics, and molecular biology. This book provides a foundation of experimental design that will be useful to all students pursuing an interest in laboratory research. This book is an enlightening and invaluable resource for anyone concerned with memory mechanisms.

* Presents a unified view of memory mechanisms from behavior to genes and drawing examples from many different brain regions, types of learning, and various animal model systems
* Includes numerous practical examples for the new investigator on how to implement research program in the area of learning and memory
* Provides a balanced treatment of the strengths and weaknesses in modern experimental design

Foreword

Preface

xiii

Acknowledgments

xvii

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

I. Introduction

(9)

A. Categories of Learning and Memory

(3)

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

(3)

II. Unconscious Learning

(11)

A. Simple Forms of Learning

(4)

B. Unconscious Learning and Unconscious Recall

(1)

C. Unconscious Learning and Subject to Conscious Recall

(3)

D. Operant Conditioning

(1)

E. Currently Popular Associative Learning Paradigms

(2)

III. Conscious Learning-Subject to Conscious and Unconscious Recall

(3)

A. Declarative Learning

(2)

B. Spatial Learning

(1)

IV. Final Note-Will Molecular Studies Change the Way We Think about Learning Behavior?

(1)

References

(2)

2. Rodent Behavioral Learning and Memory Models

I. Introduction

(1)

II. Behavioral Assessments in Rodents

(14)

A. Fear Conditioning

(5)

B. Avoidance Conditioning

(1)

C. Simple Maze Learning

(2)

D. Spatial Learning

(4)

E. Taste Learning

(3)

III. Modern Experimental Uses of Rodent Behavioral Models

(9)

A. The Four Basic Types of Experiments

(2)

B. Using Behavioral Paradigms in Block and Measure Experiments

(7)

IV. Control Experiments

(5)

A. Open Field Analysis and Elevated Plus Maze Performance

(1)

B. Rotating-Rod Performance Coordination and Motor Learning

(1)

C. Acoustic Startle and Pre-Pulse Inhibition

(1)

D. Nociception

(1)

E. Vision Tests-Light-Dark Exploration and Visual Cliff

(2)

V. Summary

(1)

References

(3)

3. The Hippocampus Serves a Role in Multimodal Information Processing, and Memory Consolidation

I. Introduction

(1)

II. Studying the Hippocampus

(3)

A. The Hippocampus Serves a Role in Information Processing-Space, Time, and Relationships

(2)

III. Hippocampal Function in Cognition

(22)

A. Space

(7)

B. Time

(5)

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

(7)

D. The Hippocampus also is Required for Memory Consolidation

(3)

IV. Summary

(1)

References

(6)

4. Long-Term Potentiation as a Physiological Phenomenon

I. Synapses in the Hippocampus-The Hippocampal Circuit

(1)

II. A Breakthrough Discovery-LTP in the Hippocampus

(8)

A. The Hippocampal Slice Preparation

(2)

B. Measuring Synaptic Transmission in the Hippocampal Slice

(3)

III. NMDA Receptor-Dependence of LTP

102

(8)

A. Pairing LTP

104

(2)

B. Dendritic Action Potentials

106

(4)

IV. NMDA Receptor-Independent LTP

110

(2)

A. 200-Hz LTP

110

(1)

B. TEA LTP

110

(1)

C. Mossy Fiber LTP in Area CA3

111

(1)

V. A Role for Calcium Influx in NMDA Receptor-Dependent LTP

112

(2)

VI. Summary

114

(1)

References

114

(3)

5. Complexities of Long-Term Potentiation

I. Introduction

117

(1)

II. Presynaptic Versus Postsynaptic Mechanisms

118

(9)

III. LTP Can Include an Increased AP Firing Component

127

(3)

IV. Temporal Integration in LTP Induction

130

(1)

V. LTP Can Be Divided into Phases

131

(11)

A. E-LTP and L-LTP-Types Versus Phases

134

(8)

VI. Spine Anatomy and Biochemical Compartmentalization

142

(2)

VII. Summary

144

(1)

References

144

(4)

6. The Biochemistry of LTP Induction

I. Introduction

148

(2)

II. LTP Induction Component 1-Mechanisms Upstream of the NMDA Receptor That Directly Regulate NMDA Receptor Function

150

(4)

A. The Structure of the NMDA Receptor

151

(1)

B. Kinase Regulation of the NMDA Receptor

151

(3)

C. Redox Regulation of the NMDA Receptor

154

(1)

D. Polyamine Regulation of the NMDA Receptor

154

(1)

III. LTP Induction Component 2Mechanisms Upstream of the NMDA Receptor That Control Membrane Depolarization

154

(9)

A. Dendritic Potassium Channels

155

(5)

B. Voltage-Dependent Sodium Channels (and Calcium Channels?)

160

(1)

C. AMPA Receptor Function

160

(1)

D. GABA Receptors

161

(2)

IV LTP Induction Component 3-The Components of the Synaptic Infrastructure That Are Necessary for the NMDA Receptor and the Synaptic Signal Transduction Machinery to Function Normally

163

(11)

A. Cell Adhesion Molecules and the Actin Matrix

164

(3)

B. Presynaptic Processes

167

(1)

C. Anchoring and Interacting Proteins of the Postsynaptic Compartment

167

(7)

V. LTP Induction Component 4Feed-Forward and Feedback Mechanisms That Regulate the Level of Calcium Attained

174

(3)

A. VDCCs

175

(1)

B. The Spine Apparatus

176

(1)

C. Mitochondrial Calcium-Handling

176

(1)

VI. LTP Induction Component 5-Extrinsic Signals That Regulate the Response to the Calcium Influx

177

(4)

A. The cAMP Gate for LTP Induction

177

(2)

B. The PLC/PKC/Neurogranin System

179

(2)

VII. LTP Induction Component 6-The Mechanisms for the Generation of the Actual Persisting Biochemical Signals

181

(1)

VIII. Summary-Models for Biochemical Information Processing in LTP Induction

182

(2)

A. Four-Way Coincidence Detection

182

(2)

References

184

(7)

7. Biochemical Mechanisms for Short-Term Information Storage at the Cellular Level Chapter Overview

191

(42)

I. Targets of the Calcium Trigger

192

(20)

A. CaMKII in E-LTP

194

(4)

B. A Second Target of Calcium: PKC

198

(12)

C. A Final Potential Target of Calcium Phospholipases

210

(1)

D. Section Summary: Mechanisms for Generating Persisting Signals in E-LTP

211

(1)

II. Targets of the Persisting Signals

212

(9)

A. AMPA Receptors in E-LTP

212

(3)

B. Direct Phosphorylation of the AMPA Receptor

215

(1)

C. Regulation of Steady-State Levels of AMPA Receptors

216

(2)

D. Silent Synapses

218

(1)

E. Proteolysis

218

(1)

F. Presynaptic Changes-Increased Release

218

(3)

G. Postsynaptic Changes in Excitability

221

(1)

III. Dendritic Protein Synthesis

221

(5)

IV. Chapter Summary

226

(1)

References

226

(7)

8. Biochemical Mechanisms for Long-Term Information Storage at the Cellular Level

Introduction

233

(2)

I. The Case for Altered Gene Expression in L-LTP

235

(5)

II. Signaling Mechanisms

240

(17)

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

241

(3)

B. Modulatory Influences That Impinge Upon This Cascade

244

(1)

C. Additional Transcription Factors Besides CREB That May Be Involved in L-LTP Induction

245

(1)

D. Gene Targets in L-LTP

245

(6)

E. mRNA Targeting and Transport

251

(2)

F. Effects of the Gene Products on Synaptic Structure

253

(4)

III. Summary-Altered Genes and Altered Circuits

257

(1)

References

258

(6)

9. LTP Does Not Equal Memory

I. LTP Does Not Equal Memory

264

(21)

A. The Block Experiment

265

(6)

B. The Mimic Experiment

271

(3)

C. The Measure Experiment

274

(11)

II. Roles for LTP

285

(13)

A. Hippocampal Information Processing

285

(3)

B. Short-Term Information Storage in the Hippocampus

288

(2)

C. Consolidation Storage of Information Within the Hippocampus for Downloading to the Cortex

290

(8)

III. Summary

298

(1)

References

298

(10)

10. Inherited Disorders of Human Memory-Mental Retardation Syndromes

I. Neurofibromatosis, Coffin-Lowry Syndrome, and the ras/ERK Cascade

308

(8)

II. Angelman Syndrome

316

(9)

III. Fragile X Syndromes

325

(7)

A. Fragile X Mental Retardation Syndrome Type 1

325

(2)

B. Fragile X Mental Retardation Type 2

327

(5)

IV. Summary

332

(1)

References

333

(5)

11. Aging-Related Memory Disorders Alzheimer's Disease

I. Aging-Related Memory Decline

338

(1)

II. What Is AD?

339

(13)

A. Stages of AD

339

(3)

B. Pathological Hallmarks of AD

342

(7)

C. Aβ42 as the Cause of AD

349

(3)

III. Genes-Familial and Late-Onset AD

352

(3)

A. APP Mutations

352

(2)

B. Presenilin Mutations

354

(1)

C. ApoE4 Alleles in AD

354

(1)

IV. Apolipoprotein E in the Nervous System

355

(1)

V. Mouse models for AD

355

(5)

A. The Tg2576 Mouse

356

(4)

VI. Summary

360

(1)

References

360

(12)

12. The Chemistry of Perpetual Memory

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

372

(1)

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

373

(4)

III. Short-Term Facilitation in Aplysia is Mediated by Changes in the Levels of Intracellular Second Messenger

377

(1)

Thus, Reaction Category 1: Altered Levels of Second Messengers

377

(1)

IV. Intermediate-Term Facilitation in Aplysia Involves Altered Gene Expression and Persistent Protein Kinase Activation-A Second Category of Reaction

378

(1)

Thus, We Have Reaction Category 2: Generation of Long Half-Life Molecules

379

(1)

V. Long-Term Synaptic Facilitation in Aplysia Involves Changes in Gene Expression and Resulting Anatomical Changes

379

(5)

VI. Three Attributes of Chemical Reactions Mediating Memory

384

(4)

A. Long-Term Memory in Mammals

384

(1)

B. Long Half-Life Reactions

385

(1)

C. Ultralong-Term Memory: Mnemogenic Chemical Reactions

386

(2)

VII. Summary: A General Chemical Model for Memory

388

(1)

References

389

(2)

Index

391


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