Mechanisms of Memory

Foreword to First EditionPreface to First EditionPreface to Second EditionAcknowledgments1. 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 References2. 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 References3. 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 References4. 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 References5. 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 References6. 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 References7. 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 References8. 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 References9. Biochemical Mechanisms for Information Storage at the Cellular Level I. Targets of the Calcium Trigger A. CaMKII 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 References10. 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 References11. 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 References12. 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 ReferencesAppendix 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 ReferencesIndex