Molecular Neurobiology of the Mammalian Brain

I Architecture and Operation of the Nervous System.- 1 The Fine Structure of the Mammalian Brain.- 1.1. Introduction.- 1.2. The Neuron.- 1.2.1. General Morphology.- 1.2.2. Synapse.- 1.2.3. Components of the Neuron.- 1.2.4. Axoplasmic Flow.- 1.2.5. Pathological Changes in the Neuron.- 1.3. Neuroglial Cells.- 1.4. Blood-Brain Barrier.- 1.5. Molecular Genetics Applied to the Nervous System.- 1.5.1. DNA Amplification and Probe Preparation.- 1.5.2. DNA Hybridization and Gene Tracing.- 1.5.3. Hybridomas and Monoclonal Antibodies.- 2 Signaling in the Nervous System.- 2.1. Signaling by Nerve Impulses.- 2.2. The Nerve Impulse.- 2.3. Ionic Mechanism of the Nerve Impulse.- 2.4. Conduction of the Nerve Impulse.- 2.5. Conduction Velocity and the Myelinated Fibers.- 2.6. Metabolic Considerations.- 2.7. Impulse Propagation in Neurons: Somata and Dendrites.- 2.8. Afterpotentials.- 2.9. Repetitive Neuronal Firing.- 3 Chemical Synaptic Transmission at Peripheral Synapses.- 3.1. Discovery of Chemical Synaptic Transmission.- 3.2. Neuromuscular Transmission.- 3.2.1. Introduction.- 3.2.2. Structural Features of the Neuromuscular Synapse.- 3.2.3. Physiological Features of the Neuromuscular Synapse.- 3.2.4. Pharmacological Features of the Neuromuscular Synapse.- 3.2.5. Quantal Liberation of Acetylcholine.- 3.2.6. Factors That Control Quantal Emission from the Nerve Terminal.- 3.2.7. Essential Role of Calcium in Quantal Release.- 3.2.8. Molecular Action of Acetylcholine.- 3.2.9. Diagrammatic Representation of Neuromuscular Synapses.- 3.3. Transmission across the Giant Synapse of the Squid Stellate Ganglion.- 3.4. Ion Channels across the Presynaptic and Postsynaptic Membranes of a Chemically Transmitting Synapse.- 3.5. Concluding Remarks.- 4 Synaptic Transmission in the Central Nervous System.- 4.1. Introduction.- 4.2. Excitatory Synaptic Action.- 4.3. Impulse Generation by Synaptic Action.- 4.4. Inhibitory Synaptic Action.- 4.5. General Features of Transmission by Postsynaptic Ionotropic Action in the Brain.- 4.6. Inhibition by Reciprocal Synapses.- 4.7. Simple Neuronal Pathways in the Brain.- 4.7.1. Pathways for la Impulses.- 4.7.2. Renshaw Cell Pathway.- 4.7.3. Hippocampal Basket Cell Pathway.- 4.7.4. Operative Features of Inhibitory Pathways.- 4.8. Presynaptic Inhibition.- 4.9. Principles of Neuronal Operation.- II Specific Neuronal Participants and Their Physiological Actions.- 5 Principles of Synaptic Biochemistry.- 5.1. Criteria for Neurotransmitters.- 5.1.1. Anatomical.- 5.1.2. Chemical.- 5.1.3. Physiological.- 5.1.4. Pharmacological.- 5.2. Classification of Neurotransmitters.- 5.3. Properties of Receptors.- 5.3.1. Kinetic Criteria.- 5.3.2. Pharmacological Criteria.- 5.3.3. Anatomical Criteria.- 5.3.4. Chemical Criteria.- 5.4. Coupler and Effector Systems.- 5.4.1. Cyclic Nucleotides as Second Messengers.- 5.4.2. Calcium and Its Binding Proteins.- 5.4.3. Polyphosphoinositides.- 5.5. Summary.- 6 Putative Excitatory Neurons: Glutamate and Aspartate.- 6.1. Introduction.- 6.2. Chemistry and Metabolism of Glutamate and Aspartate.- 6.3. Anatomical Distribution of Glutamate and Aspartate.- 6.4. Physiology of Glutamate and Aspartate.- 6.4.1. Receptor Sites.- 6.4.2. Binding Sites.- 6.4.3. Excitotoxicity.- 6.5. Pharmacology and Pathology of Glutamate and Aspartate.- 6.6. Summary.- 7 Inhibitory Amino Acid Neurotransmitters.- 7.1. Introduction.- 7.2. Chemistry and Metabolism of ?-Aminobutyric Acid.- 7.3. Anatomical Distribution of ?-Aminobutyric Acid Pathways in brain.- 7.3.1. Cerebellum.- 7.3.2. Hippocampus.- 7.3.3. Basal Ganglia.- 7.3.4. Raphe System.- 7.3.5. Diencephalon.- 7.3.6. Spinal Cord.- 7.3.7. Olfactory Bulb.- 7.3.8. Retina.- 7.3.9. Peripheral ?-Aminobutyric Acid.- 7.4. Physiology of ?-Aminobutyric Acid.- 7.5. Pharmacology of ?-Aminobutyric Acid.- 7.5.1. Receptor Site Modulators.- 7.5.2. Synthesis Promotion or Inhibition.- 7.5.3. Storage and Release Mechanisms.- 7.5.4. Pump Inhibition.- 7.5.5. Inhibition of Metabolism.- 7.5.6. Receptor Agonists and Antagonists.- 7.6. Pathology of ?-Aminobutyric Acid.- 7.7. Chemistry and Metabolism of Glycine.- 7.8. Anatomical Distribution of Glycine.- 7.9. Physiology, Pharmacology, and Pathology of Glycine.- 7.10. Other Suggested Inhibitory Amino Acid Transmitters.- 7.10.1. Taurine.- 7.10.2. Proline.- 7.10.3. Pipecolic Acid (Piperidine-2-carboxylic Acid).- 7.10.4. Other Amino Acids with Inhibitory Action.- 7.11. Summary.- 8 Cholinergic Neurons.- 8.1. Introduction.- 8.2. Chemistry of Acetylcholine.- 8.2.1. Synthesis of Acetylcholine.- 8.2.2. Destruction of Acetylcholine.- 8.2.3. Storage, Release, and Turnover of Acetylcholine.- 8.3. Anatomy of Cholinergic Neurons: Cholinergic Cell Groups and Pathways..- 8.3.1. Medial Forebrain Complex.- 8.3.2. Striatal Interneurons.- 8.3.3. Motor Nuclei for Peripheral Nerves.- 8.3.4. Parabrachial Complex.- 8.3.5. Reticular Formation.- 8.3.6. Minor Cholinergic Systems.- 8.4. Physiological Actions of Acetylcholine and the Cholinergic Receptors.- 8.4.1. Types of Cholinergic Receptors.- 8.4.2. Iontophoretic Effects of Acetylcholine on Central Neurons.- 8.4.3. Separation of the Acetylcholine Receptor.- 8.5. Pharmacology of Acetylcholine.- 8.5.1. Muscarinic Agonists 25.- 8.5.2. Muscarinic Antagonists.- 8.5.3. Nicotinic Agonists.- 8.5.4. Nicotinic Antagonists.- 8.5.5. Release Inhibitors and Promoters.- 8.5.6. Anticholinesterases.- 8.5.7. Synthesis Stimulators and Inhibitors.- 8.6. Pathology of Cholinergic Systems.- 8.6.1. Myasthenia Gravis.- 8.6.2. Senile Dementia of the Alzheimer Type.- 8.6.3. Diseases That Affect Anterior Horn Cells.- 8.7. Summary.- 9 Catecholamine Neurons.- 9.1. Introduction.- 9.2. Chemistry of Catecholamine Neurons.- 9.2.1. Synthesis of Catecholamines.- 9.2.2. Catabolism of Catecholamines.- 9.3. Storage, Release, and Turnover of Catecholamines.- 9.3.1. Storage of Catecholamines.- 9.3.2. Release of Catecholamines.- 9.3.3. Reuptake of Synaptically Released Catecholamines.- 9.3.4. Turnover of Catecholamines.- 9.3.5. In Vivo Control of Catecholamine Synthesis.- 9.4. Anatomy of Catecholamine Neurons.- 9.4.1. Methods and General Anatomical Considerations.- 9.4.2. Anatomical Distribution of Dopamine.- 9.4.3. Anatomical Distribution of Noradrenaline.- 9.4.4. Anatomical Distribution of Adrenaline.- 9.5. Physiology and Pharmacology of Dopamine.- 9.5.1. Physiology of Dopamine.- 9.5.2. Pharmacology of Dopamine.- 9.6. Physiology and Pharmacology of Noradrenaline.- 9.6.1. Physiology of Noradrenaline.- 9.6.2. Pharmacology of Noradrenaline.- 9.7. Physiology and Pharmacology of Adrenaline.- 9.8. Summary.- 10 Serotonin and Other Brain Indoles.- 10.1. Introduction.- 10.2. Chemistry and Metabolism of Serotonin.- 10.2.1. Synthesis of Serotonin.- 10.2.2. Destruction of Serotonin.- 10.2.3. Other Routes of Serotonin Metabolism.- 10.3. Storage, Release, and Turnover of Serotonin.- 10.3.1. Storage and Release of Serotonin.- 10.3.2. Control of Serotonin Synthesis.- 10.4. Anatomy of Serotonin Neurons.- 10.4.1. Anatomical Distribution of Serotonin.- 10.4.2. Serotonin Pathways and Terminals.- 10.5. Physiological Actions of Serotonin and Serotonin Receptors.- 10.5.1. Serotonin Receptors.- 10.5.2. Serotonin and Sleep.- 10.5.3. Serotonin and Sex.- 10.5.4. Serotonin and Pain.- 10.5.5. Serotonin, Mood, and Mental Illness.- 10.6. Pharmacology of Serotonin.- 10.6.1. Agents That Are Toxic to Serotonin Neurons.- 10.6.2. Inhibitors of Tryptophan Hydroxylase.- 10.6.3. Inhibitors of 5-Hydroxytryptophan Decarboxylase.- 10.6.4. Inhibitors of Monoamine Oxidase.- 10.6.5. Inhibitors of Serotonin Uptake.- 10.6.6. Inhibitors of Storage.- 10.6.7. Receptor Site Agonists and Antagonists.- 10.7. Melatonin and Other Indoles.- 10.7.1. Melatonin and the Pineal Gland.- 10.7.2. Tryptamine in the Brain.- 10.8. Summary.- 11 Other Heterocyclic Putative Neurotransmitters: Histamine and Purines.- 11.1. Introduction.- 11.2. Chemistry of Histamine.- 11.2.1. Synthesis of Histamine.- 11.2.2. Destruction of Histamine.- 11.2.3. Storage, Release, and Turnover of Neuronal and Mast Cell Histamine.- 11.3. Anatomy of Histamine Neurons.- 11.4. Physiological Actions of Histamine and Histamine Receptors.- 11.5. Pharmacology of Histamine.- 11.6. Purines.- 11.6.1. Chemistry of Purines.- 11.6.2. Distribution and Anatomy of Adenosine Systems.- 11.6.3. Physiology of Adenosine.- 11.6.4. Other Suggested Purine Neurotransmitters.- 11.7. Summary.- 12 The Prominent Peptides.- 12.1. Introduction.- 12.2. Chemistry of the Neuropeptides.- 12.2.1. Structural Considerations.- 12.2.2. Synthesis of the Neuropeptides.- 12.2.3. Destruction of the Neuropeptides.- 12.2.4. Biotransformation of the Neuropeptides.- 12.3. Distribution and Anatomy of Neuropeptide Systems.- 12.3.1. Methodology.- 12.3.2. General Comments on Distribution.- 12.3.3. Hypothalamus.- 12.3.4. Limbic System.- 12.3.5. Cortex.- 12.3.6. Basal Ganglia.- 12.3.7. Brain Stem and Nucleus Tractus Solitarius.- 12.3.8. Cerebellum.- 12.3.9. Other Systems.- 12.4. Physiology of the Neuropeptides.- 12.4.1. Iontophoretic Effects, Release, Binding Sites, and Second Messengers.- 12.4.2. General Physiology of the Neuropeptides.- 12.5. Pharmacology and Pathology of the Neuropeptides.- 12.5.1 Pharmacology of the Neuropeptides.- 12.5.2. Pathology of the Neuropeptides.- 12.6. Summary.- III The Integrative Aspects of Brain Function.- 13 The Building of the Brain and Its Adaptive Capacity.- 13.1. Building of the Brain.- 13.1.1. Introduction.- 13.1.2. Building of the Cerebral Neocortex.- 13.1.3. Building of the Cerebellum.- 13.1.4. Building of Brain Nuclei and the Hippocampus.- 13.2. Principles of Neuronal Recognition and Connectivity.- 13.2.1. Introduction.- 13.2.2. Neuronal Connectivity in Mammals.- 13.2.3. New Synaptic Connectivities Developed by Activation.- 13.2.4. Regressive Events in Neurogenesis.- 13.2.5. Transplantation.- 13.3. Dependence of Neurons on Trophic Factors.- 13.3.1. Introduction.- 13.3.2. Primary Retrograde Deprivation and Axonal Section.- 13.3.3. Hypothesis of Chromatolysis.- 13.3.4. Secondary and Tertiary Retrograde Transneuronal Degeneration..- 13.3.5. Anterograde Transneuronal Deprivation.- 13.4. Nerve Growth Factor, Other Peptide Neuronotrophic Factors, and Gangliosides.- 13.4.1. Nerve Growth Factor.- 13.4.2. Other Peptide Neuronotrophic Factors.- 13.4.3. Gangliosides.- 13.5. Neurons and Neuronotrophic Factors.- 13.6. Aging and Cell Death.- 13.7. General Conclusions.- 14 Control of Movement by the Brain.- 14.1. Introduction.- 14.2. Motor Control from the Spinal Cord and Brain Stem.- 14.3. Motor Control from the Cerebral Cortex.- 14.3.1. Motor Cortex.- 14.3.2. Discharge of Motor Pyramidal Cells.- 14.3.3. Cerebral Cortex Control of the Motor Cortex: Supplementary Motor Area.- 14.3.4. Arrangement of Pyramidal Cells in Colonies.- 14.3.5. ?-Motoneurons and ?-Motoneurons and the ?-Loop.- 14.3.6. Pyramidal Tract Innervation of ?-Motoneurons and ?-Motoneurons.- 14.3.7. Projection of la Fibers to the Cerebral Cortex.- 14.4. Motor Control by the Cerebellum.- 14.4.1. Introduction.- 14.4.2. Neuronal Structure.- 14.4.3. Neuronal Functions.- 14.4.4. Cerebrocerebellar Pathways.- 14.4.5. Spinocerebellar Connectivities.- 14.4.6. General Comments on the Cerebellum.- 14.5. Motor Control from the Basal Ganglia.- 14.5.1. Introduction.- 14.5.2. Anatomical Interconnections of the Basal Ganglia.- 14.5.3. Neurotransmitters in the Basal Ganglia.- 14.5.4. Physiology, Pharmacology, and Pathology of the Basal Ganglia..- 14.5.5. Summary of Motor Control by the Basal Ganglia.- 14.6. Synthesis of Various Neuronal Mechanisms Concerned with the Control of Voluntary Movement.- 15 Basic Behavioral Patterns.- 15.1. Introduction.- 15.2. Genotropic Action.- 15.3. Central Coordination of Behavior.- 15.4. Central Amines and Behavior.- 15.5. Psychoactive Drugs.- 15.5.1. Neuroleptics.- 15.5.2. Antidepressants.- 15.5.3. Stimulants.- 15.5.4. Anxiolytic Agents.- 15.5.5. Hallucinogenic Agents.- 15.5.6. Summary on Drugs.- 15.6. The Mystery of Mental Illness.- 15.6.1. Hypotheses of Schizophrenia.- 15.6.2. Hypotheses of Affective Psychoses.- 15.7. Summary.- 16 Neuronal Mechanisms Involved in Learning and Memory.- 16.1. Introduction.- 16.2. Structural and Functional Changes Possibly Related to Learning and Memory.- 16.3. Hippocampus as a Model for Memory.- 16.3.1. Calcium and Long-Term Potentiation.- 16.3.2. Synaptic Spine.- 16.3.3. Possible Presynaptic Contributions to Long-Term Potentiation...- 16.3.4. Comprehensive Hypothesis for Long-Term Potentiation.- 16.4. Locations of Engrams.- 16.5. Cognitive Learning and Memory.- 16.5.1. Neural Pathways Involved in the Laying Down of Cognitive Memories According to the Instruction-Selection Hypothesis.- 16.5.2. A Model for Cognitive Memory Built on Long-Term Potentiation.- 16.5.3. Duration of Long-Term Potentiation and Cognitive Memory.- 16.5.4. Recall of Memory.- 16.5.5. Final Comments on Cognitive Memory.- 16.6. Neurochemistry of Learning.- 16.7. Learning in the Motor System.- 16.7.1. Introduction.- 16.7.2. Learning of Automatic Movements.- 16.7.3. Learning of Motor Skills by Animals.- 16.7.4. Learning of Motor Skills by Humans.- 17 Perception, Speech, and Consciousness.- 17.1. Cerebral Cortex.- 17.1.1. Modular Operation of the Neocortex.- 17.2. Perception.- 17.2.1. Introduction.- 17.2.2. Cutaneous Perception (Somesthesis).- 17.2.3. Pain.- 17.2.4. Visual Perception.- 17.2.5. Auditory Perception.- 17.2.6. Olfactory Perception.- 17.2.7. Emotional Coloring of Conscious Perceptions.- 17.3. Language Centers of the Human Brain.- 17.3.1. Introduction.- 17.3.2. Aphasia.- 17.3.3. Experiments on Exposed Brains.- 17.3.4. Intracarotid Injections of Sodium Amytal.- 17.3.5. Dichotic Listening Test.- 17.3.6. Anatomical Substrates of Speech Mechanisms.- 17.4. Language and Self-Consciousness.- 17.4.1. Effects of Global Cerebral Lesions.- 17.4.2. Dominant and Minor Hemispheres.- 17.5. Relationship of Brain to Mind.- 17.5.1. Introduction.- 17.5.2. Testing of Mind-Brain Theories.- 17.5.3. A New Hypothesis of Mind-Brain Interaction.- Epilogue.- References.