Mechanisms of Memory

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

Recall

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

Habituation

Sensitization

Dishabituation

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

Amnesias

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

Anatomy

Habits

Stereotyped movements

Sequence learning

IV. Prodigious memory

Mnemonists

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

Nociception

Vision Tests--Light-Dark Exploration and Visual Cliff

B. Fear conditioning

Cue-plus-contextual fear conditioning

Cued fear conditioning

Contextual Fear Conditioning

Extinction

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

CHAPTER 7.

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

TEA 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

CaMKII

V. Summary

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

I. Targets of the Calcium Trigger

A. CaMKII

B. Adenylyl 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

FMRP

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

Observe/Determine

Block

Mimic

Measure

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