| |
| |
| Preface | |
| |
| |
| Preface to the First Edition | |
| |
| |
| Preface to the Second Edition | |
| |
| |
| |
| Introductory Orientation | |
| |
| |
| |
| Outline of Nervous Systems | |
| |
| |
| |
| Vertebrate Nervous Systems | |
| |
| |
| |
| Cells of the Nervous Systems | |
| |
| |
| |
| Neurons | |
| |
| |
| |
| Glia | |
| |
| |
| |
| Organisation of Synapses | |
| |
| |
| |
| Organisation of Neurons in the Brain | |
| |
| |
| |
| The Conformation of Informational Macromolecules | |
| |
| |
| |
| Proteins | |
| |
| |
| |
| Primary Structure | |
| |
| |
| |
| Secondary Structure | |
| |
| |
| |
| Tertiary Structure | |
| |
| |
| |
| Quaternary Structure | |
| |
| |
| |
| Molecular Chaperones | |
| |
| |
| |
| Nucleic Acids | |
| |
| |
| |
| DNA | |
| |
| |
| |
| RNA | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Information Processing in Cells | |
| |
| |
| |
| The Genetic Code | |
| |
| |
| |
| Replication | |
| |
| |
| |
| 'DNA Makes RNA and RNA Makes Protein' | |
| |
| |
| |
| Transcription | |
| |
| |
| |
| Post-transcriptional Processing | |
| |
| |
| |
| Translation | |
| |
| |
| |
| Antisense and triplex oligonucleotides | |
| |
| |
| |
| Control of the Expression of Genetic Information | |
| |
| |
| |
| Genomic Control | |
| |
| |
| |
| Transcriptional Control | |
| |
| |
| |
| Oncogenes, protooncogenes and IEGs | |
| |
| |
| |
| Post-transcriptional Control | |
| |
| |
| |
| Translational Control | |
| |
| |
| |
| Post-translational Control | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Molecular Evolution | |
| |
| |
| |
| Mutation | |
| |
| |
| |
| Point Mutations | |
| |
| |
| |
| Proof-reading and Repair Mechanisms | |
| |
| |
| |
| Chromosomal Mutations | |
| |
| |
| |
| Protein Evolution | |
| |
| |
| |
| Evolutionary Development of Protein Molecules and Phylogenetic Relationships | |
| |
| |
| |
| Evolutionary Relationships of Different Proteins | |
| |
| |
| |
| Evolution by Differential Post-transcriptional and Post-translational Processing: the Opioids and Other Neuroactive Peptides | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Manipulating Biomolecules | |
| |
| |
| |
| Restriction Endonucleases | |
| |
| |
| |
| Separation of Restriction Fragments | |
| |
| |
| |
| Restriction Maps | |
| |
| |
| |
| Recombination | |
| |
| |
| |
| Cloning | |
| |
| |
| |
| Plasmids | |
| |
| |
| |
| Phage | |
| |
| |
| |
| Cosmids | |
| |
| |
| |
| Bacterial Artificial Chromosomes (BACs) | |
| |
| |
| |
| Yeast Artifical Chromosomes (YACs) | |
| |
| |
| |
| Isolating Bacteria Containing Recombinant Plasmids or Phage | |
| |
| |
| |
| The 'Shotgun' Construction of 'Genomic' Gene Libraries | |
| |
| |
| |
| A Technique for Finding a Gene in the Library | |
| |
| |
| |
| Construction of a 'cDNA' Gene Library | |
| |
| |
| |
| Fishing for Genes in a cDNA Library | |
| |
| |
| |
| Positional Cloning | |
| |
| |
| |
| The Polymerase Chain Reaction (PCR) | |
| |
| |
| |
| Sequence Analysis of DNA | |
| |
| |
| |
| Prokaryotic Expression Vectors for Eukaryotic DNA | |
| |
| |
| |
| Xenopus Oocyte as an Expression Vector for Membrane Proteins | |
| |
| |
| |
| Site-directed Mutagenesis | |
| |
| |
| |
| Gene Targeting and Knockout Genetics | |
| |
| |
| |
| Targeted Gene Expression | |
| |
| |
| |
| Hybridisation Histochemistry | |
| |
| |
| |
| DNA Chips | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Genomics | |
| |
| |
| |
| Some History | |
| |
| |
| |
| Methodology | |
| |
| |
| |
| Salient Features of the Human Genome | |
| |
| |
| |
| The Genes of Neuropathology | |
| |
| |
| |
| Single Nucleotide Polymorphisms (SNPs) | |
| |
| |
| |
| Other Genomes | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Biomembranes | |
| |
| |
| |
| Lipids | |
| |
| |
| |
| Phospholipids | |
| |
| |
| |
| Glycolipids | |
| |
| |
| |
| Cholesterol | |
| |
| |
| |
| Membrane Order and Fluidity | |
| |
| |
| |
| Membrane Asymmetry | |
| |
| |
| |
| Proteins | |
| |
| |
| |
| Mobility of Membrane Proteins | |
| |
| |
| |
| Synthesis of Biomembranes | |
| |
| |
| |
| Myelin and Myelination | |
| |
| |
| |
| The Submembranous Cytoskeleton | |
| |
| |
| |
| Junctions Between Cells | |
| |
| |
| |
| Tight Junctions | |
| |
| |
| |
| Gap Junctions | |
| |
| |
| |
| Gap Junctions and Neuropathology | |
| |
| |
| |
| Deafness | |
| |
| |
| |
| Cataract | |
| |
| |
| |
| Charcot-Marie-Tooth (Type 2) Disease | |
| |
| |
| |
| Spreading Hyperexcitability (Epilepsy) and Hypoexcitability (Spreading Depression) | |
| |
| |
| |
| Conclusion and Forward Look | |
| |
| |
| |
| G-protein-coupled Receptors | |
| |
| |
| |
| Messengers and Receptors | |
| |
| |
| |
| The 7TM Serpentine Receptors | |
| |
| |
| |
| G-proteins | |
| |
| |
| |
| The GTPase superfamily | |
| |
| |
| |
| G-protein Collision-coupling Systems | |
| |
| |
| |
| Effectors and Second Messengers | |
| |
| |
| |
| Adenylyl Cyclases | |
| |
| |
| |
| PIP[subscript 2]-phospholipase (Phospholipase C-[beta]) | |
| |
| |
| |
| Synaptic Significance of 'Collision-coupling' Systems | |
| |
| |
| |
| Networks of G-protein Signalling Systems | |
| |
| |
| |
| The Adrenergic Receptor (AR) | |
| |
| |
| |
| The Muscarinic Acetylcholine Receptor (mAChR) | |
| |
| |
| |
| Metabotropic Glutamate Receptors (mGluRs) | |
| |
| |
| |
| Neurokinin Receptors (NKRs) | |
| |
| |
| |
| Cannabinoid Receptors (CBRs) | |
| |
| |
| |
| Rhodopsin | |
| |
| |
| |
| Cone Opsins | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Pumps | |
| |
| |
| |
| Energetics | |
| |
| |
| |
| The Na[superscript +] + K[superscript +] Pump | |
| |
| |
| |
| The Calcium Pump | |
| |
| |
| |
| Calmodulin | |
| |
| |
| |
| Other Pumps and Transport Mechanisms | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Ligand-gated Ion Channels | |
| |
| |
| |
| The Nicotinic Acetylcholine Receptor | |
| |
| |
| |
| Structure | |
| |
| |
| |
| Function | |
| |
| |
| |
| Development | |
| |
| |
| |
| Pathologies | |
| |
| |
| |
| CNS Acetylcholine Receptors | |
| |
| |
| |
| Evolution of the nAChRs | |
| |
| |
| |
| The GABA[subscript A] Receptor | |
| |
| |
| |
| Pathology | |
| |
| |
| |
| The Glycine Receptor | |
| |
| |
| |
| Ionotropic Glutamate Receptors (iGluRs) | |
| |
| |
| |
| AMPA Receptors | |
| |
| |
| |
| KA Receptors | |
| |
| |
| |
| NMDA Receptors | |
| |
| |
| |
| The inositol triphosphate (IP[subscript 3] or InsP[subscript 3]) receptor | |
| |
| |
| |
| Purinoceptors | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Voltage-gated Channels | |
| |
| |
| |
| The KcsA Channel | |
| |
| |
| |
| Neuronal K[superscript +] Channels | |
| |
| |
| |
| 2TM(1P) Channels; Kir Channels | |
| |
| |
| |
| 4TM(2P) Channels; K[superscript +] Leak Channels | |
| |
| |
| |
| 6TM(1P) Channels; K[subscript v] Channels | |
| |
| |
| |
| Cyclic nucleotide-gated (CNG) channels | |
| |
| |
| |
| Ca[superscript 2+] Channels | |
| |
| |
| |
| Structure | |
| |
| |
| |
| Diversity | |
| |
| |
| |
| Biophysics | |
| |
| |
| |
| Na[superscript +] Channels | |
| |
| |
| |
| Structure | |
| |
| |
| |
| Diversity | |
| |
| |
| |
| Biophysics | |
| |
| |
| |
| Ion Selectivity and Voltage Sensitivity | |
| |
| |
| |
| Ion Selectivity | |
| |
| |
| |
| Voltage Sensitivity | |
| |
| |
| |
| Voltage-Sensitive Chloride Channels | |
| |
| |
| |
| ClC Channels | |
| |
| |
| |
| Cln Channels | |
| |
| |
| |
| Phospholemman | |
| |
| |
| |
| Channelopathies | |
| |
| |
| |
| Potassium Channels | |
| |
| |
| |
| Calcium Channels | |
| |
| |
| |
| Sodium Channels | |
| |
| |
| |
| Chloride Channels | |
| |
| |
| |
| Evolution of Ion Channels | |
| |
| |
| |
| Conclusion and Forward Look | |
| |
| |
| |
| Resting Potentials and Cable Conduction | |
| |
| |
| |
| Measurement of the Resting Potential | |
| |
| |
| |
| The Origin of the Resting Potential | |
| |
| |
| |
| Electrotonic Potentials and Cable Conduction | |
| |
| |
| |
| Length | |
| |
| |
| |
| Diameter | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Sensory Transduction | |
| |
| |
| |
| Chemoreceptors | |
| |
| |
| |
| Chemosensitivity in Prokaryocytes | |
| |
| |
| |
| Chemosensitivity in Vertebrates | |
| |
| |
| |
| Photoreceptors | |
| |
| |
| |
| Retinitis pigmentosa | |
| |
| |
| |
| Mechanoreceptors | |
| |
| |
| |
| A Prokaryote Mechanoreceptor | |
| |
| |
| |
| Mechanosensitivity in Caenorhabditis elegans | |
| |
| |
| |
| Mechanosensitivity in Vertebrates: Hair Cells | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| The Action Potential | |
| |
| |
| |
| Voltage-clamp Analyses | |
| |
| |
| |
| Patch-clamp Analyses | |
| |
| |
| |
| Propagation of the Action Potential | |
| |
| |
| |
| Early history of the impulse | |
| |
| |
| |
| Initiation of the Impulse | |
| |
| |
| |
| Switching off neurons by manipulating K[superscript +] channels | |
| |
| |
| |
| Rate of Propagation | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| The Neuron as a Secretory Cell | |
| |
| |
| |
| Neurons and Secretions | |
| |
| |
| |
| Synthesis in the Perikaryon | |
| |
| |
| |
| Co-translational Insertion | |
| |
| |
| |
| The Golgi Body and Post-translational Modification | |
| |
| |
| |
| Transport Along the Axon | |
| |
| |
| |
| Microfilaments | |
| |
| |
| |
| Intermediate Filaments (IFs) | |
| |
| |
| |
| Subcellular geography of protein biosynthesis in neurons | |
| |
| |
| |
| Microtubules (MTs) | |
| |
| |
| |
| The Axonal Cytoskeleton | |
| |
| |
| |
| Axoplasmic Transport Summarised | |
| |
| |
| |
| Exocytosis and Endocytosis at the Synaptic Terminal | |
| |
| |
| |
| Vesicle Mustering | |
| |
| |
| |
| The Ca[superscript 2+] Trigger | |
| |
| |
| |
| Vesicle Docking | |
| |
| |
| |
| Transmitter Release | |
| |
| |
| |
| Dissociation of Fusion Complex and Retrieval and Reconstitution of Vesicle Membrane | |
| |
| |
| |
| Refilling of Vesicle | |
| |
| |
| |
| Vesicular neurotransmitter transporters | |
| |
| |
| |
| Termination of Transmitter Release | |
| |
| |
| |
| Modulation of Release | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Neurotransmitters and Neuromodulators | |
| |
| |
| |
| Acetylcholine | |
| |
| |
| |
| Criteria for neurotransmitters | |
| |
| |
| |
| Amino Acids | |
| |
| |
| |
| Excitatory Amino Acids (EAAs): Glutamic Acid and Aspartic Acid | |
| |
| |
| |
| Inhibitory Amino Acids (IAAs): [gamma]-Aminobutyric Acid and Glycine | |
| |
| |
| |
| Otto Loewi and vagusstoff | |
| |
| |
| |
| Serotonin (=5-Hydroxytryptamine, 5-HT) | |
| |
| |
| |
| Catecholamines | |
| |
| |
| |
| Dopamine (DA) | |
| |
| |
| |
| Noradrenaline (=Norepinephrine, NE) | |
| |
| |
| |
| Purines | |
| |
| |
| |
| Cannabinoids | |
| |
| |
| |
| Reuptake neurotransmitter transporters | |
| |
| |
| |
| Peptides | |
| |
| |
| |
| Substance P | |
| |
| |
| |
| Enkephalins | |
| |
| |
| |
| Cohabitation of Peptides and Non-peptides | |
| |
| |
| |
| Nitric Oxide (NO) | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| The Postsynaptic Cell | |
| |
| |
| |
| Synaptosomes | |
| |
| |
| |
| The Postsynaptic Density | |
| |
| |
| |
| Electrophysiology of the Postsynaptic Membrane | |
| |
| |
| |
| The Excitatory Synapse | |
| |
| |
| |
| Cajal, Sherrington and the beginnings of synaptology | |
| |
| |
| |
| The Inhibitory Synapse | |
| |
| |
| |
| Interaction of EPSPs and IPSPs | |
| |
| |
| |
| Ion Channels in the Postsynaptic Membrane | |
| |
| |
| |
| Second Messenger Control of Ion Channels | |
| |
| |
| |
| Second Messenger Control of Gene Expression | |
| |
| |
| |
| The Pinealocyte | |
| |
| |
| |
| Conclusion and Forward Look | |
| |
| |
| |
| Developmental Genetics of the Brain | |
| |
| |
| |
| Introduction: 'Ontology Recapitulates Phylogeny' | |
| |
| |
| |
| Establishing an Anteroposterior (A-P) Axis in Drosophila | |
| |
| |
| |
| Initial Subdivision of the Drosophila Embryo | |
| |
| |
| |
| The A-P Axis in Vertebrate Central Nervous Systems | |
| |
| |
| |
| Segmentation Genes in Mus musculus | |
| |
| |
| |
| Homeosis and Homeotic Mutations | |
| |
| |
| |
| Homeobox Genes | |
| |
| |
| |
| Homeobox Genes and the Early Development of the Brain | |
| |
| |
| |
| POU Genes and Neuronal Differentiation | |
| |
| |
| |
| Sequential Expression Of Transcription Factors in Drosophila CNS | |
| |
| |
| |
| Pax-6: Developmental Genetics of Eyes and Olfactory Systems | |
| |
| |
| |
| Other Genes Involved in Neuronal Differentiation | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Epigenetics of the Brain | |
| |
| |
| |
| The Origins of Neurons and Glia | |
| |
| |
| |
| Neural Stem Cells | |
| |
| |
| |
| Tracing Neuronal Lineages | |
| |
| |
| |
| Retrovirus Tagging | |
| |
| |
| |
| Enhancer Trapping | |
| |
| |
| |
| Morphogenesis of Neurons | |
| |
| |
| |
| Morphogenesis of the Drosophila Compound Eye | |
| |
| |
| |
| Growth Cones | |
| |
| |
| |
| Pathfinding | |
| |
| |
| |
| Eph receptors and ephrins | |
| |
| |
| |
| Cell Adhesion Molecules (CAMs) | |
| |
| |
| |
| Growth Factors and Differential Survival | |
| |
| |
| |
| Neurotransmitters as growth factors | |
| |
| |
| |
| Morphopoietic Fields | |
| |
| |
| |
| Functional Sculpting | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Memory | |
| |
| |
| |
| Some Definitions | |
| |
| |
| |
| Classical Conditioning | |
| |
| |
| |
| Operant Conditioning | |
| |
| |
| |
| Short- and Long-term Memory | |
| |
| |
| |
| Relation Between STM and LTM | |
| |
| |
| |
| Where is the Memory Trace Located? | |
| |
| |
| |
| Invertebrate Systems | |
| |
| |
| |
| Thermal Conditioning in C. elegans | |
| |
| |
| |
| Drosophila | |
| |
| |
| |
| Aplysia and the Molecular Biology of Memory | |
| |
| |
| |
| The Memory Trace in Mammals | |
| |
| |
| |
| Post-tetanic Potentiation and Long-term Potentiation | |
| |
| |
| |
| Fibre Pathways in the Hippocampus | |
| |
| |
| |
| Perforant and Schaffer Collateral Fibres | |
| |
| |
| |
| The CRE Site Again | |
| |
| |
| |
| Mossy Fibre Pathway | |
| |
| |
| |
| Histology | |
| |
| |
| |
| Non-genomic Mechanisms | |
| |
| |
| |
| Dendritic spines | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Some Pathologies | |
| |
| |
| |
| Neuroses, Psychoses and the Mind/Brain Dichotomy | |
| |
| |
| |
| Prions and Prion Diseases | |
| |
| |
| |
| Phenylketonuria (PKU) | |
| |
| |
| |
| Fragile X Syndrome (FraX) | |
| |
| |
| |
| Neurofibromatoses | |
| |
| |
| |
| Motor Neuron Disease (MND) | |
| |
| |
| |
| Huntington's Disease (=Chorea) (HD) | |
| |
| |
| |
| Depression | |
| |
| |
| |
| Endogenous Depression | |
| |
| |
| |
| Exogenous Depression | |
| |
| |
| |
| Neurochemistry of Depression | |
| |
| |
| |
| Stress and Depression | |
| |
| |
| |
| Parkinson's Disease (PD) | |
| |
| |
| |
| [alpha]-Synuclein | |
| |
| |
| |
| Alzheimer's Disease (AD) | |
| |
| |
| |
| Diagnosis | |
| |
| |
| |
| Aetiology | |
| |
| |
| |
| Molecular Pathology | |
| |
| |
| |
| Environmental Influences: Aluminium | |
| |
| |
| |
| The BAPtist Proposal: an Amyloid Cascade Hypothesis | |
| |
| |
| |
| Therapy | |
| |
| |
| |
| Conclusion | |
| |
| |
| |
| Molecules and Consciousness | |
| |
| |
| |
| Units | |
| |
| |
| |
| Data | |
| |
| |
| |
| Genes | |
| |
| |
| |
| Physical Models of Ion Conduction and Gating | |
| |
| |
| Acronyms and Abbreviations | |
| |
| |
| Glossary | |
| |
| |
| Bibliography | |
| |
| |
| Index of Neurological Disease | |
| |
| |
| Index | |