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By J. David Sweatt, Baylor College of Medicine, Houston, Texas, U.S.A.
Description Many who work on the cellular and molecular processes of learning and memory are tempted to throw up their hands in frustration and conclude
that the problem is insoluble. Human learning and memory is likely the most highly evolved and sophisticated biological process in existence.
This book represents the first step at beginning to put together the complex puzzle of the molecular basis of memory. Sweatt creates
a framework of thinking about synaptic plasticity and memory at the molecular level; one which recognizes and begins to incorporate this
extreme biochemical complexity into our thinking about memory. Now in its second edition this is currently the only book on the market
that takes this approach.
All chapters are fully revised, and four new chapters have been added. The book is adaptable for courses
for senior level undergraduates and, first and second year graduate students. It will be of use to students interested in the medical
professions and graduate students interested in translational aspects of basic memory research at a time when translational research
is becoming a priority area for research funding agencies in the US and internationally.
Audience
Senior undergraduates and graduate students studying memory, as well as those interested in the medical professions and in translational aspects of basic memory research.
Contents
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
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