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  • EEn

  • From Messengers to Molecules: Memories Are Made of These

    • Copyright Info

    • Dedication

    • TOC

      • Editors

      • Contributors

      • Preface

      • Abbreviations

      • Section 1. Ions and Ion Channels

        • Chapter 1.1 - Calcium

          • Abstract

          • Introduction

          • Ca2+ Influx

            • Intracellular Release And Storage

              • Ip3 Receptors

              • Ryanodine Receptors

            • Buffering And Sequestration

          • Neurotransmitter Release

          • Modulation Of Channel Activity

            • Unknown

              • Long-term Changes Of Ca2+-influx Via Memory-specific K+ Channel Regulation

          • Signal Transduction Cascades

            • Information Coding

            • Axon Growth

            • Synaptic Plasticity

              • Long-term Modifications Of Synapses

              • Postsynaptic Switch

            • Synaptic Interaction And Associative Learning

            • Oxygen-sensing And Hypoxic Injury

            • Gene Expression

          • Alzheimer’s Disease

            • Unknown

              • -amyloid

          • Conclusion

        • Chapter 1.2 - Potassium

          • Abstract

          • Introduction

          • How Can K+ Channels Contribute To Learning And Memory?

            • K+ Channels And Invertebrate Learning And Memory

              • Studies In Hermissenda Crassicornis

              • Studies In Aplysia Californica

              • Studies In Drosophila Melanogaster

            • Studies In Other Invertebrates

            • K+ Channels And Mammalian Learning And Memory

              • Modulation Of The Slow Afterhyperpolarization (sahp) As A L&m Mechanism

              • Modulation Of A-type K+ Channels As A L&m Mechanism

          • Conclusion

            • Acknowledgements

      • Section 2. Principle Neurotransmitters

        • Chapter 2.1 - Glutamate Receptors

          • Abstract

          • Introduction

          • Glutamate Receptor Function In Learning And Memory Formation

            • Spatial Learning

              • The Open-field Water Maze

              • The 8-arm Radial Maze

              • Elevated TAnd Y-maze Protocols

              • Other Spatial Learning Paradigms

            • Conditioning Of Fear Responses

              • Conditioning To Context And Cue

              • Fear Potentiated Startle

              • Other Fear Conditioning Tasks

            • Avoidance Learning

              • One-trial Inhibitory Avoidance In 1 Day-old Chicks

              • Step-down Inhibitory Avoidance

              • Step Through Passive Avoidance

              • Active Avoidance

            • Olfactory And Gustatory Learning Paradigms

            • Other Tasks

          • Conclusions And Remaining Questions

        • Chapter 2.2 - γ-Amino-Butyric Acid (GABA)

          • Abstract

          • Introduction

          • Gabaergic Drugs And Memory Formation: Peripheral Administrations

            • Gabaergic Antagonists

              • Picrotoxin

              • Bicuculline

            • Gabaergic Agonists

              • Muscimol

              • Baclofen

          • Gabaergic Drugs And Memory: Genotype-dependent Effects

          • Gabaergic Drugs And The State-dependency Hypothesis

          • Gabaergic Drugs And Memory Formation: Administrations Into Brain Structures

          • Interaction With Other Systems

            • Gaba-opioids Interactions

            • Gaba-benzodiazepines Interactions

            • Gaba-ethanol Interactions

        • Chapter 2.3 - Acetylcholine: I. Muscarinic Receptors

          • Abstract

          • Introduction

            • Anatomy Of Brain Cholinergic Pathways

          • Muscarinic Receptors

            • Subtypes—transduction Mechanisms

            • Cns Distribution Of The Muscarinic Receptors

            • Alterations In Machr Expression In Behaviorally-induced Plasticity

            • Muscarinic Receptors In Aging And Alzheimer’s Disease

            • Muscarinic Receptors Theta Rhythm And Hippocampal Long Term Potentiation (ltp)

          • Which Cognitive Processes Depend On The Activation Of Muscarinic Receptors?

            • Cognitive Alterations Induced By The Blockade Of Muscarinic Receptors

            • Cognitive Alteration Induced By Lesions In The Cholinergic Pathways

            • Cognitive Processes Associated With Changes In Cholinergic Activity

          • Effects Of Direct And Indirect Selective Muscarinic Receptor Agonists On Learning And Memory: Therapeutic Implications

          • Conclusions

        • Chapter 2.4 - Acetylcholine: II. Nicotinic Receptors

          • Abstract

          • Introduction

          • Neuronal Nachrs

            • Subtypes

            • Localization

          • Memory

          • Attention

          • Rewarding/incentive Effects

          • Other Effects

          • Closing Remarks

            • Acknowledgements

        • Chapter 2.5 - Serotonin

          • Abstract

          • Introduction

          • Role Of 5-ht In Memory: Global Strategies

          • Serotonergic-cholinergic Interactions

          • 5-ht Receptors In Memory Systems

            • Basic Neurobiological Data

              • 5-ht Receptors And Linkage To Second Messenger: Signaling Pathways

              • Anatomical And Cellular Compartment Locations

            • Integrating Behavioral And Neurobiological Data

              • Receptors That Inhibit Adenylyl Cyclase

              • Receptors That Stimulate Adenylyl Cyclase

              • Receptors That Stimulate Phospholipase C

              • A Ligand-gated Ion Channel

          • Conclusions And Perspectives

            • Role Of 5-ht In AgeOr Alzheimer’s Disease-related Memory Decline

            • New Tools For Research And Therapeutical Strategies

        • Chapter 2.6 - Dopamine

          • Abstract

          • Introduction: Dopamine Receptors In The Brain

            • Dopaminergic Systems In The Central Nervous System

            • Dopamine Receptor Subtypes

          • Functional Studies Using A Systemic Approach

            • Da Receptors And Locomotor Activity

            • Da Receptors And Reward

            • Da Receptors And Eating And Drinking

            • Da Receptors And Cognition

          • Functional Studies Using A Central Approach

            • Dopaminergic Depletions And Cognitive Impairments

            • Intracerebral Infusion Of Dopaminergic Drugs And Cognitive Processes

          • Epilogue

        • Chapter 2.7 - Adrenaline and Noradrenaline

          • Abstract

          • Pharmacology Of AAnd ß-adrenoceptors In The Central Nervous System

            • Sources Of Noradrenaline In The Cns

            • Stimulus For Noradrenaline Release

            • Adrenoceptor Subtypes And Signal Transduction Pathways

              • Signal Transduction Pathways Of A1-adrenoceptors

              • Signal Transduction Pathways Of A2-adrenoceptors

              • Signal Transduction Pathways Of ß-adrenoceptors

            • Distribution Of Adrenoceptor Subtypes In The Brain

              • Localization Of Adrenoceptor Binding

              • Localization Of Mrna

              • Localization Of A1-adrenoceptors

              • Localization Of A2-adrenoceptors

              • Localization Of ß-adrenoceptors

          • Factors Affecting Drug Action At Adrenoceptors

          • Memory Studies With Adrenoceptor Agonists And Antagonists In Rats

            • Amygdala

            • Hippocampus

            • Prefrontal Cortex

            • Olfactory Bulb

            • Locus Coeruleus

          • Memory Studies With Adrenoceptor Agonists And Antagonists In Chicks

            • Roles For Adrenoceptor Subtypes In The Imhv

              • -adrenoceptors

            • -adrenoceptors

          • Roles For Adrenoceptor Subtypes In The Lpo

            • -adrenoceptors

          • Summary

        • Chapter 2.8 - Histamine

          • Abstract

          • Introduction

          • The Histaminergic Neuron System

          • The Role Of The Tuberomammillary Nucleus Projection System In Neural Plasticity And Functional Recovery

          • The Role Of The Histaminergic Neuronal System In The Control Of Reinforcement

          • The Role Of The Histaminergic Neuronal System In The Control Of Learning And Mnemonic Processes

            • Lesion Studies

            • Pharmacological Approach

          • Tuberomammillary Modulation Of Hippocampal Signal Transfer

          • Conclusions

            • Acknowledgments

        • Chapter 2.9 - Adenosine and Purines

          • Abstract

          • Origin Of Adenosine In The Extracellular Fluid

          • Adenosine Receptors

          • Adenosine And Learning

            • Adenosine Receptor Subtypes And Learning

            • Cellular Actions Of Adenosine

          • Adenosine And Synaptic Plasticity

            • Paired-pulse Inhibition

          • Interactions Between Adenosine And Cholinergic Neurotransmission

            • Cellular Mechanisms Of Adenosine / Acetylcholine Interactions

            • Adenosine And Acetylcholine Release

          • Interactions Between Purines And Glutamate Receptors

            • Adenosine And Glutamate Release

            • Adenosine And Glutamate Receptor Interactions

          • Other Receptor Interactions

            • Adenosine Receptor Interactions

            • Adenosine And Dopamine

            • Adenosine And Peptides

          • The Effects Of Ageing On Adenosine Receptors

          • Trophic Functions Of Nucleosides

          • Nucleotides And Synaptic Plasticity

            • Atp And Synaptic Plasticity

          • Summary

      • Section 3. Neuromodulators

        • Chapter 3.1 - Cannabinoids

          • Abstract

          • Introduction

          • Cannabinoid Receptors

          • Cannabinoid Receptor Ligands

          • Cannabinoid Receptors Modulate Memory Formation

            • Spatial Learning

              • Water Maze

              • Radial Arm Maze

              • T-and Y Maze Procedures

              • Delayed-match-to-position

            • Conditioning Of Fear

            • Avoidance Tasks

              • Inhibitory Avoidance

              • Active Avoidance

            • Olfactory And Gustatory Memory Paradigms

            • Other Paradigms

          • Conclusions

        • Chapter 3.2 - Opioids

          • Abstract

          • Introduction

          • Distribution Of Opioid Peptides And Their Receptors In The Hippocampus

            • Opioid Peptides

            • Receptors

          • Effects Of Opioid Receptor Ligands On Long-term Potentiation In Hippocampal Regions (table 2)

          • Effects Of Opioid Receptor Ligands On Learning And Memory In Hippocampal Regions

          • Effects Of Opioid Receptor Ligands On Learning And Memory Tasks (table 3)

          • Ameliorating Effects Of Opioid Receptor Ligands On Models Of Learning And Memory Impairment (table 4)

          • Future Expectation

        • Chapter 3.3 - Neuropeptides

          • Introduction

          • Posterior Pituitary Peptides (vasopressin, Oxytocin)

          • Acth/msh And Opioid Peptides

          • Hypophyseotropic Peptides (crf, Somatostatin)

          • Brain-gut Peptides (cck, Neuropeptide Y, Galanin)

          • Substance P

          • Natriuretic Peptides, Angiotensin

          • Amyloid Peptides

          • Conclusions

        • Chapter 3.4 - Nerve Growth Factors and Neurotrophins

          • Abstract

          • Introduction

          • Neurotrophin Expression And Regulation Of Neurogenesis During Development

          • Neurotrophin Receptors

          • Nerve Growth Factor And The Basal Forebrain Cholinergic System

          • Behavioral Studies Of Ngf Administrations

            • Does Early Icv Nfg Injections Alter The Development Of Spatial Abilities In Immature Rats?

            • Are These Effects Maintained In Adulthood?

              • Rats Treated On Days 12 And 13

              • Rats Treated On Days 2 And 3

          • Discussion

        • Chapter 3.5 - Eph Receptors and Their Ephrin Ligands in Neural Plasticity

          • Abstract

          • Introduction

          • The Promiscuous Family Of Eph Receptors

            • Eph Receptors Are In The Right Places And At The Right Time

            • Eph Receptors: “new” Players In The Adult Brain

          • Function Of Eph Receptors In The Normal Brain: Role In Plasticity And Memory

          • Mechanisms Mediating Eph Action: The First Working Hypotheses

          • Concluding Remarks

        • Chapter 3.6 - Cortiocosteroids

          • Abstract

          • Glucocorticoid Hormones And Receptors

            • Glucocorticoids And The Hypothalamic-pituitary-adrenal (hpa) Axis

            • Corticosteroid Receptors In The Brain

          • Role Of Glucocorticoids On Memory Consolidation

            • Manipulation Of The Degree Of Stress Involved In The Training Task

            • Inhibition Of Glucocorticoid Secretion

            • Inhibition Of Glucocorticoid Action

            • Potentiation Of Glucocorticoid Action

          • Neural Mechanisms Involved In Glucocorticoid Actions On Memory Consolidation

            • Brain Regions Implicated In Glucocorticoid Effects On Memory Consolidation

            • Cellular And Molecular Mechanisms Involved On Glucocorticoid Effects On Memory Consolidation

          • Effects Of Chronic Exposure To Elevated Glucocorticoid Levels On Cognitive And Neural Function

            • Neural Consequences Of Chronic Glucocorticoid Exposure

            • Cognitive Consequences Of Chronic Glucocorticoid Exposure

          • Conclusion

      • Section 4. Second Messengers and Enzymes

        • Chapter 4.1 - Adenylyl Cyclases

          • Abstract

          • Introduction

          • Adenylyl Cyclases And Memory Formation In Invertebrates

            • Molecular Mechanisms Underlying Memory In Aplysia Californica

          • The Drosophila System

          • A Specific Role For Mammalian Adenylyl Cyclases In Learning And Memory Processes: Heterogeneity Of Mammalian Adenylyl Cyclases

            • Diversity In The Regulation Of Mammalian Adenylyl Cyclases By G Proteins Ca2+ Signals And Phosphorylation

            • Regulation By G-proteins

            • Regulation By Ca2+

            • Regulation By Protein Kinases

            • Potential Targets Of Camp

            • The Specific Distribution And Expression Levels Of Mammalian Adenylyl Cyclases In Brain

            • Adenylyl Cyclase And Long-term Potentiation

            • Are Ca2+-stimulated Adenylyl Cyclases Critical For Memory

            • Adenylyl Cyclases Up Or Down Depending On Task Demands

          • Summary And Conclusions

        • Chapter 4.2 - Phospholipases and Oxidases

          • Abstract

          • Introduction

          • Phospholipases

            • What Are Phospholipases?

            • How Are Phospholipases Activated?

          • Arachidonic Acid (ara), A Second Messenger

          • Release Of Ara

          • Time Course Of Release

          • Targets Of Ara

          • Ara And Metabolites Of Ara As Transmitters And ‘retrograde Messengers’ In Synaptic Plasticity

            • How To Ensure Selectivity Of Ara Messenger Activity

            • The Role Of Ara In Ltp Formation

            • Learning Experiments: Evidence For The Role Of Phospholipase Activity In Memory Formation

            • A Different Second Messenger Released By Pla2: Platelet-activated Factor (paf)

          • Oxygenases That Are Of Importance In Memory Formation

            • Lipoxygenases

          • Cyclooxygenases

            • What Are Cyclooxygenases?

            • Learning Experiments: Evidence For The Role Of Cox-2 Activity In Memory Formation

            • Cooperation Of Ara And Metabolites Of Ara As Messengers In Neuronal Systems

          • The Timing Of Memory Formation

            • Discrete Time Windows Of Messenger Activity

          • Defined Steps In Memory Formation

          • A Potential Role For Defined Time Windows Of Messenger Systems In Memory Formation

        • Chapter 4.3 - Protein Kinase A

          • Abstract

          • Introduction

          • ShortAnd Long-term Memory

          • One-trial Avoidance

          • The Camp/pka Signaling Pathway

          • Pka Involvement In Long-term Memory Formation

          • Pka Involvement In Short-term Memory Formation

          • Pka Involvement In Memory Retrieval

          • Pka Involvement In Extinction

          • Summary

        • Chapter 4.4 - Protein Kinase C

          • Abstract

          • Introduction

          • Protein Kinase C: Who Is It?

            • Pkc: A Family Of Phosphorylating Enzymes

            • Involvement Of Anchoring Proteins In Pkc Activation

          • Pkc In Synaptic Plasticity

            • Early Evidence For Pkc Involvement In Ltp

            • In Which Ltp Phase Is Pkc Involved?

            • Is Pkc Requirement For Ltp Presynaptic, Postsynaptic Or Both?

            • Pkc Isozymes: Who Is Doing What?

            • Recent Findings: The Role Of Pkc In Synaptic Plasticity Revisited

          • Evidence For The Involvement Of Pkc In Cognitive Processes

            • Habituation Sensitization And Classical Conditioning In Invertebrates

            • Classical Conditioning

            • Passive Avoidance

            • Operant Conditioning

            • Perceptual Discrimination Learning And Perceptual Memory

            • Cognitive Mapping And Spatial Discrimination

            • Motor Activity, Anxiety, Stress

          • Pkc And Neuronal Pathologies Impairing Cognition

            • Chronic Neurodegeneration

              • Alzheimer’s Disease (ad)

              • Basal Ganglia Diseases

              • Amyotrophic Lateral Sclerosis (als)

            • Acute Neurodegeneration

              • Cerebral Ischemia

              • Brain Trauma

            • Affective Disorders

              • Bipolar

              • Unipolar And Obsessive Compulsive Disorder

          • Pharmacological Modulation Of Pkc: The Goal Of Isoenzyme Selectivity

            • Pkc Inhibitors

              • Staurosporine Derivatives

              • Peptides

              • Antisense Oligodeoxynucleotides (odn)

            • Pkc Activators

          • Conclusions

        • Chapter 4.5 - CaMKinase II

          • Abstract

          • Introduction

          • Camkii: Synaptic Plasticity And Memory Processing

          • Downstream Effectors Of The Camkii Cascade

          • Camkiv: A New (and Important) Player In The Plasticity Team

          • Concluding Remarks

        • Chapter 4.6 - MAP Kinases

          • Abstract

          • Introduction And Background

            • The Erk/mapk Cascade

            • Tar Gets Of The Erk Cascade

            • Potassium Channel Modulation

            • Kv4.2 As An Effector For Erk

          • Hippocampal Involvement In Learning

            • Long-term Potentiation

            • Ltp As A Model For Learning And Memory

          • Erk In Hippocampal Synaptic Plasticity

            • Theta-like Ltp Induction Paradigms Require Erk Activation

          • A Necessity For Erk Activation For Mammalian Learning

            • Spatial Learning Requires Erk

            • Dissociation Of Contextual Fear Conditioning And Hfs-ltp

          • Specific Contributions Of Erk Isoforms To Ltp And Learning

          • Biochemical Attributes That Make Erk Suited For Memory Formation

            • Signal Amplification

            • Signal Integration

            • Te Mporal Integration

            • Response Coordination

          • Summary

            • Acknowledgements

        • Chapter 4.7 - Phosphatases

          • Abstract

          • Introduction

            • Protein Phosphorylation: What Is It And Why Is It Significant?

            • Enzymes That Regulate Phosphorylation In The Brain

            • Protein Serine/threonine Phosphatases In The Brain

            • Why Phosphorylation Might Be Critical For Memory Formation

            • Capacity For Rapid Responsivity And Reversibility

            • Capacity For Specificity And Precision

            • Capacity For Signal Integration

            • Capacity To Prolong Changes And Induce Permanent Functional Alterations

          • Phosphorylation In Information Storage Processes

            • Early Empirical Evidence Of A Role For Phosphorylation In Memory Formation

            • Long Term Potentiation: A Model For Increasing Synaptic Efficacy

            • Protein Phosphatases In Ltp

            • Long-term Depression: A Model For Decreasing Synaptic Efficacy

            • Lisman’s Bi-directional Model Of Synaptic Plasticity

            • Protein Phosphatases In Ltd

          • Phosphatase Involvement In Invertebrate Memory Models

          • Protein Phosphatases In Aplysia Learning And Memory

            • Protein Phosphatases In Drosophila Learning And Memory

          • Phosphorylation In Vertebrate Memory Models

            • Kinases And Phosphatases In Chick Memory Formation

            • Pp2a

            • Pp1

            • Pp2b

            • Protein Phosphatases In Rodent Learning And Memory

          • Conclusion

        • Chapter 4.8 - Nitric Oxide

          • Abstract

          • Introduction

          • Regulation Of No Synthesis In The Brain

          • Role Of No In Ltp And Ltd

          • Role Of No In Memory Processes

            • Spatial Learning And Memory

            • Fear Memories

            • Olfactory Memory

            • Motor Learning

          • Learning And Memory-associated Changes In No Production In The Brain

          • Conclusions

      • Section 5. Transcription Factors, Genes and Proteins

        • Chapter 5.1 - CREB

          • Abstract

          • Introduction

          • Structure

          • Activation

          • Creb And Electrophysiological Studies Of Long-term Plasticity In Aplysia

          • Creb And Memory In Drosophila

          • Creb And Ltm In Mammals

            • Tar Geted Disruption Of Creb Function In A Mouse

          • Gaining Temporal And Spatial Control Of Creb Function In Mammals

            • Detecting Creb Activation During Learning

            • Creb And Reconsolidation

          • Conclusions

            • Acknowledgements

        • Chapter 5.2 - Immediate-Early Genes

          • Abstract

          • Introduction

          • Learning Activates Iegs

          • A Link Between Cholinergic System And Iegs

          • Iegs And Their Relation To Stress

          • Summary

            • Acknowledgements

        • Chapter 5.3 - Protein Synthesis: I. Pharmacology

          • Abstract

          • Asking About The ‘where’ And ‘when’ Of Learning-related Protein Synthesis

          • Inhibitors Of Protein Synthesis

            • Transcription Inhibitors

            • Translation Inhibitors

          • Effects Of Protein Synthesis Inhibitors On Memory Formation

            • Invertebrates

              • Aplysia Californica

              • Hermissenda Crassicornis

              • Insects

            • Birds

              • Imprinting

              • Passive Avoidance Learning

              • Song Learning

            • Mammals

              • Fear Conditioning

              • Conditioned Taste Aversion

              • Avoidance Learning

              • Discrimination Learning

              • Spatial Learning

              • Electrophysiological Models

          • Principle Findings And Future Perspectives In Protein Synthesis Inhibitor Research

            • The “when”

            • The “where”

        • Chapter 5.4 - Protein Synthesis: II. New Proteins

          • Abstract

          • Introduction

            • A Brief History

            • Protein Synthesis Inhibitors

            • Interim Summary

            • The Rate Of Protein Synthesis

            • The Posttranslational Modifications

            • The ‘local’ Protein Synthesis

          • Present Time

            • De Novo Protein Synthesis (with Paraphernaliae)

          • Conclusion

      • Section 6. Morphological Changes in Synapses and Neurones

        • Chapter 6.1 - Learning-Induced Synaptogenesis and Structural Synaptic Remodeling

          • Abstract

          • Introduction

          • Patterns Of Synaptogenesis Elicited By Behavioral Learning

            • Net Synaptogenesis Resulting From Learning

          • Specific Synaptogenesis Related To Learning-induced Adult Neurogenesis

            • Specific Synaptogenesis Related To Learning-induced Formation Of Multiple-synapse Boutons

          • Pattern Of Structural Synaptic Remodeling Elicited By Behavioral Learning

            • Increase In The Number Of Perforated Axospinous Synapses Following Learning: A Possible Morphological Correlate Of The Conversio

          • Enlargement Of Postsynaptic Densities Following Learning: A Possible Morphological Correlate Of The Conversion Of Postsynaptical

          • Conclusions

            • Acknowledgements

        • Chapter 6.2 - Cell Adhesion Molecules

          • Abstract

          • Introduction

          • Is Net Synapse Formation A Correlate Of Learning?

            • Results From Studies Employing Long-term Potentiation

            • Results From Studies Employing Behavioural Paradigms

          • Do Cell Adhesion Molecules Have A Role In Learning?

            • Cam Structure And Function

            • Cams And Learning-induced Synaptic Plasticity

          • Do Cell Adhesion Molecules Have A Temporal Role In Learning?

          • Can Cell Adhesion Molecules Reveal Memory Pathway?

            • Ncam Polysialylation

            • Regulation Of Ncam Polysialylation State

            • The Hnk1 Carbohydrate Epitope

          • What About Neurogenesis In Learning?

          • Perspective

            • Acknowledgements

      • Section 7. Learning about Memory by Studying Brain Dysfunction

        • Chapter 7.1 - Animal and Human Amnesia: The Cholinergic Hypothesis Revisited

          • Identifying Memory Dysfunction

          • Acetylcholine And Memory: From A Key Neurotransmitter To The Functional Dynamics Of Interactive Processes

            • The Cholinergic Hypothesis Of Memory: Lesion Studies

          • Cholinergic Alterations Induced By Learning And Memory Testing

            • Should The Cholinergic Hypothesis Be Re-examined?

          • From Assessment To Alleviation Of Age-related Memory Impairments In Mice

            • Modelling Human Age-related Memory Deficits

            • Assessing Similarities Of Memory Impairments In Senescent And Hippocampal Lesioned Subjects

            • Alleviating The Selective Age-related Memory Deficit

          • Conclusion

        • Chapter 7.2 - Aging and the Calcium Homeostasis

          • Abstract

          • Introduction

          • Altered Ca2+ Homeostasis In Aging

          • Altered Ca2+ Homeostasis And Age-related Learning Deficits

          • Alterations In Ca2+-mediated Plasticity In Aging: Implications For Learning

          • Paradigms Used To Study Age-related Learning Deficits

            • Trace Eyeblink Conditioning

            • Morris Water Maze

          • Learning-related Changes In Hippocampal Ca1 Pyramidal Neurons—postsynaptic Excitability Increases In Learning

            • Components Of The Ahp Altered In Learning

            • Postsynaptic Excitability In Ca1 Hippocampal Pyramidal Neurons Decreases In Aging: Implications For Age-related Learning Deficit

          • Mechanisms Underlying Aging-related Enhancement In The Siahp

          • Siahp As A Link Between Age-related Changes In Ca2+ Homeostasis And Learning

Nội dung

NEUROSCIENCE INTELLIGENCE UNIT Gernot Riedel and Bettina Platt RIEDEL • PLATT NIU From Messengers to Molecules: Memories Are Made of These From Messengers to Molecules: Memories Are Made of These NEUROSCIENCE INTELLIGENCE UNIT From Messengers to Molecules: Memories Are Made of These Gernot Riedel, Ph.D Bettina Platt, Ph.D School of Medical Sciences College of Life Sciences and Medicine University of Aberdeen Foresterhill, Aberdeen, U.K LANDES BIOSCIENCE / EUREKAH.COM GEORGETOWN, TEXAS U.S.A KLUWER ACADEMIC / PLENUM PUBLISHERS NEW YORK, NEW YORK U.S.A FROM MESSENGERS TO MOLECULES: MEMORIES ARE MADE OF THESE Neuroscience Intelligence Unit Landes Bioscience / Eurekah.com Kluwer Academic / Plenum Publishers Copyright ©2004 Eurekah.com and Kluwer Academic / Plenum Publishers All rights reserved No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system; for exclusive use by the Purchaser of the work Printed in the U.S.A Kluwer Academic / Plenum Publishers, 233 Spring Street, New York, New York, U.S.A 10013 http://www.wkap.nl/ Please address all inquiries to the Publishers: Landes Bioscience / Eurekah.com, 810 South Church Street Georgetown, Texas, U.S.A 78626 Phone: 512/ 863 7762; FAX: 512/ 863 0081 www.Eurekah.com www.landesbioscience.com From Messengers to Molecules: Memories Are Made of These, edited by Gernot Riedel and Bettina Platt, Landes / Kluwer dual imprint / Landes series: Neuroscience Intelligence Unit ISBN: 0-306-47862-5 While the authors, editors and publisher believe that drug selection and dosage and the specifications and usage of equipment and devices, as set forth in this book, are in accord with current recommendations and practice at the time of publication, they make no warranty, expressed or implied, with respect to material described in this book In view of the ongoing research, equipment development, changes in governmental regulations and the rapid accumulation of information relating to the biomedical sciences, the reader is urged to carefully review and evaluate the information provided herein Library of Congress Cataloging-in-Publication Data From messengers to molecules : memories are made of these / [edited by] Gernot Riedel, Bettina Platt p ; cm (Neuroscience intelligence unit) Includes bibliographical references and index ISBN 0-306-47862-5 Neurochemistry Neurotransmitters Neurotransmitter receptors I Riedel, Gernot II Platt, Bettina III Series: Neuroscience intelligence unit (Unnumbered) [DNLM: Memory physiology Ion Channels Learning physiology Memory Disorders Neurotransmitters Transcription Factors WL 102 F9308 2004] QP356.3.F76 2004 612.8'042 dc22 2004001884 Dedication To our children Daniel and Lisa Sophie, for wonderful memories CONTENTS Preface ix Abbreviations xxi Section Ions and Ion Channels 1.1 Calcium Miao-Kun Sun and Daniel L Alkon Ca2+ Influx Neurotransmitter Release Modulation of Channel Activity Signal Transduction Cascades Alzheimer’s Disease 14 1.2 Potassium 20 Jeffrey Vernon and Karl Peter Giese How Can K+ Channels Contribute to Learning and Memory? 22 Section Principle Neurotransmitters 2.1 Glutamate Receptors 39 Gernot Riedel, Jacques Micheau and Bettina Platt Glutamate Receptor Function in Learning and Memory Formation 43 2.2 γ-Amino-Butyric Acid (GABA) 72 Claudio Castellano, Vincenzo Cestari and Alessandro Ciamei GABAergic Drugs and Memory Formation: Peripheral Administrations 73 GABAergic Drugs and Memory: Genotype-Dependent Effects 75 GABAergic Drugs and the State-Dependency Hypothesis 76 GABAergic Drugs and Memory Formation: Administrations into Brain Structures 77 Interaction with Other Systems 82 2.3 Acetylcholine: I Muscarinic Receptors 90 Giancarlo Pepeu and Maria Grazia Giovannini Muscarinic Receptors 93 Which Cognitive Processes Depend on the Activation of Muscarinic Receptors? 98 Effects of Direct and Indirect Selective Muscarinic Receptor Agonists on Learning and Memory: Therapeutic Implications 103 2.4 Acetylcholine: II Nicotinic Receptors 113 Joyce Besheer and Rick A Bevins Neuronal nAChRs 113 Memory 115 Attention 117 Rewarding/Incentive Effects 118 Other Effects 120 2.5 Serotonin 125 Marie-Christine Buhot, Mathieu Wolff and Louis Segu Role of 5-HT in Memory: Global Strategies 126 Serotonergic-Cholinergic Interactions 128 5-HT Receptors in Memory Systems 128 2.6 Dopamine 143 Jan P.C de Bruin Functional Studies Using a Systemic Approach 145 Functional Studies Using a Central Approach 148 2.7 Adrenaline and Noradrenaline 155 Marie E Gibbs and Roger J Summers Pharmacology of α- and β-Adrenoceptors in the Central Nervous System 155 Factors Affecting Drug Action at Adrenoceptors 159 Memory Studies with Adrenoceptor Agonists and Antagonists in Rats 160 Memory Studies with Adrenoceptor Agonists and Antagonists in Chicks 163 Roles for Adrenoceptor Subtypes in the LPO 169 2.8 Histamine 174 Rüdiger U Hasenöhrl and Joseph P Huston The Histaminergic Neuron System 174 The Role of the Tuberomammillary Nucleus Projection System in Neural Plasticity and Functional Recovery 176 The Role of the Histaminergic Neuronal System in the Control of Reinforcement 178 The Role of the Histaminergic Neuronal System in the Control of Learning and Mnemonic Processes 181 Tuberomammillary Modulation of Hippocampal Signal Transfer 187 2.9 Adenosine and Purines 196 Trevor W Stone, M-R Nikbakht and E Martin O’Kane Origin of Adenosine in the Extracellular Fluid 196 Adenosine Receptors 196 Adenosine and Learning 197 Adenosine and Synaptic Plasticity 199 Interactions between Adenosine and Cholinergic Neurotransmission 201 Interactions between Purines and Glutamate Receptors 203 Other Receptor Interactions 205 The Effects of Ageing on Adenosine Receptors 210 Trophic Functions of Nucleosides 210 Nucleotides and Synaptic Plasticity 211 Section Neuromodulators 3.1 Cannabinoids 224 Lianne Robinson, Bettina Platt and Gernot Riedel Cannabinoid Receptors 224 Cannabinoid Receptor Ligands 225 Cannabinoid Receptors Modulate Memory Formation 226 3.2 Opioids 246 Makoto Ukai, Ken Kanematsu, Tsutomu Kameyama and Takayoshi Mamiya Distribution of Opioid Peptides and Their Receptors in the Hippocampus 246 Effects of Opioid Receptor Ligands on Long-Term Potentiation in Hippocampal Regions 249 Effects of Opioid Receptor Ligands on Learning and Memory in Hippocampal Regions 251 Effects of Opioid Receptor Ligands on Learning and Memory Tasks 251 Ameliorating Effects of Opioid Receptor Ligands on Models of Learning and Memory Impairment 251 3.3 Neuropeptides 256 David De Wied and Gábor L Kovács Posterior Pituitary Peptides (Vasopressin, Oxytocin) 256 ACTH/MSH and Opioid Peptides 261 Hypophyseotropic Peptides (CRF, Somatostatin) 263 Brain-Gut Peptides (CCK, Neuropeptide Y, Galanin) 266 Substance P 270 Natriuretic Peptides, Angiotensin 272 Amyloid Peptides 277 3.4 Nerve Growth Factors and Neurotrophins 286 Catherine Brandner Neurotrophin Expression and Regulation of Neurogenesis during Development 287 Neurotrophin Receptors 287 Nerve Growth Factor and the Basal Forebrain Cholinergic System 287 Behavioral Studies of NGF Administrations 289 Discussion 295 3.5 Eph Receptors and Their Ephrin Ligands in Neural Plasticity 300 Robert Gerlai The Promiscuous Family of Eph Receptors 300 Function of Eph Receptors in the Normal Brain: Role in Plasticity and Memory 302 Mechanisms Mediating Eph Action: The First Working Hypotheses 306 3.6 Corticosteroids 314 Carmen Sandi Glucocorticoid Hormones and Receptors 314 Role of Glucocorticoids on Memory Consolidation 317 Neural Mechanisms Involved in Glucocorticoid Actions on Memory Consolidation 321 Effects of Chronic Exposure to Elevated Glucocorticoid Levels on Cognitive and Neural Function 324 Section Second Messengers and Enzymes 4.1 Adenylyl Cyclases 330 Nicole Mons and Jean-Louis Guillou Adenylyl Cyclases and Memory Formation in Invertebrates 331 The Drosophila System 332 A Specific Role for Mammalian Adenylyl Cyclases in Learning and Memory Processes: Heterogeneity of Mammalian Adenylyl Cyclases 333 4.2 Phospholipases and Oxidases 349 Christian Hölscher Phospholipases 350 Arachidonic Acid (ArA), a Second Messenger 351 Release of ArA 352 Time Course of Release 352 Targets of ArA 352 ArA and Metabolites of ArA As Transmitters and ‘Retrograde Messengers’ in Synaptic Plasticity 353 Oxygenases That Are of Importance in Memory Formation 357 Cyclooxygenases 358 The Timing of Memory Formation 362 Defined Steps in Memory Formation 362 A Potential Role for Defined Time Windows of Messenger Systems in Memory Formation 363 4.3 Protein Kinase A 369 Monica R.M Vianna and Ivan Izquierdo Short- and Long-Term Memory 370 One-Trial Avoidance 372 The cAMP/PKA Signaling Pathway 372 PKA Involvement in Long-Term Memory Formation 373 PKA Involvement in Short-Term Memory Formation 375 PKA Involvement in Memory Retrieval 378 PKA Involvement in Extinction 379 4.4 Protein Kinase C 383 Xavier Noguès, Alessia Pascale, Jacques Micheau and Fiorenzo Battaini Protein Kinase C: Who Is It? 384 PKC in Synaptic Plasticity 386 Evidence for the Involvement of PKC in Cognitive Processes 389 PKC and Neuronal Pathologies Impairing Cognition 395 Pharmacological Modulation of PKC: The Goal of Isoenzyme Selectivity 400 4.5 CaMKinase II 411 Martín Cammarota and Jorge H Medina CaMKII: Synaptic Plasticity and Memory Processing 412 Downstream Effectors of the CaMKII Cascade 416 CaMKIV: A New (and Important) Player in the Plasticity Team 418 4.6 MAP Kinases 425 Joel C Selcher, Edwin J Weeber and J David Sweatt Hippocampal Involvement in Learning 429 ERK in Hippocampal Synaptic Plasticity 433 A Necessity for ERK Activation for Mammalian Learning 435 Specific Contributions of ERK Isoforms to LTP and Learning 440 Biochemical Attributes That Make ERK Suited for Memory Formation 442 4.7 Phosphatases 448 Pauleen C Bennett and Kim T Ng Phosphorylation in Information Storage Processes 458 Phosphatase Involvement in Invertebrate Memory Models 462 Protein Phosphatases in Aplysia Learning and Memory 463 Phosphorylation in Vertebrate Memory Models 464 4.8 Nitric Oxide 480 Kiyofumi Yamada and Toshitaka Nabeshima Regulation of NO Synthesis in the Brain 480 Role of NO in LTP and LTD 481 Role of NO in Memory Processes 483 Learning and Memory-Associated Changes in NO Production in the Brain 487 ...NEUROSCIENCE INTELLIGENCE UNIT Gernot Riedel and Bettina Platt RIEDEL • PLATT NIU From Messengers to Molecules: Memories Are Made of These From Messengers to Molecules: Memories Are Made of These NEUROSCIENCE... of These NEUROSCIENCE INTELLIGENCE UNIT From Messengers to Molecules: Memories Are Made of These Gernot Riedel, Ph.D Bettina Platt, Ph.D School of Medical Sciences College of Life Sciences and... classical N-type 4 From Messengers to Molecules: Memories Are Made of These P-type channels are potently blocked by ω-Aga-IVA, with an IC50 of 1-2 nM In contrast, α1A channels in oocytes are much less

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