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 Nucleus.- 1.2.4 Organelles.- 1.2.5 Surface Membrane of Neurons and Nerve Fibers.- 1.2.6 Pathological Changes in the Neuron.- 1.3 Neuroglial Cells.- 1.4 The Blood-Brain Barrier.- 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 The 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 Properties of the Neuromuscular Synapse..- 3.2.5 Quantal Liberation of Acetylcholine.- 3.2.6 Factors Controlling Quantal Emission from the Nerve Terminal.- 3.2.7 The Essential Role of Calcium in Quantal Release.- 3.2.8 Molecular Action of Acetylcholine (ACH).- 3.2.9 Postsynaptic Events in Neuromuscular Transmission.- 3.2.10 Diagrammatic Representation of Neuromuscular Synapses..- 3.3 Transmission across the Giant Synapse of the Squid Stellate Ganglion.- 3.4 Ionic Channels across the Presynaptic and Postsynaptic Membranes of a Chemically Transmitting Synapse.- 3.5 Concluding Statements.- 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 Action in the Brain.- 4.6 Inhibition by Reciprocal Synapses.- 4.7 Simple Neuronal Pathways in the Brain.- 4.7.1 Pathways for Ia 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 Cholinergic Neurons.- 5.1 Introduction.- 5.2 Anatomy of Cholinergic Neurons.- 5.3 Chemistry of Acetylcholine.- 5.3.1 Synthesis of ACh.- 5.3.2 Destruction of ACh.- 5.3.3 Storage, Release, and Turnover of ACh.- 5.4 Physiological Action of ACh and the Cholinergic Receptor.- 5.4.1 Types of Cholinergic Receptors.- 5.4.2 Metabotropic Actions of ACh.- 5.4.3 Iontophoretic Effects of ACh on Central Neurons.- 5.4.4 Separation of the ACh Receptor.- 5.4.5 Overall Central Nervous System Effects of ACh.- 5.5 Pharmacology of ACh.- 5.5.1 Nicotinic Antagonists.- 5.5.2 Muscarinic Antagonists.- 5.5.3 Nicotinic Agonists.- 5.5.4 Muscarinic Agonists.- 5.5.5 Synthesis Inhibitors.- 5.5.6 Release Inhibitors and Promoters.- 5.5.7 Anticholinesterases.- 5.6 Summary.- 6 Putative Excitatory Neurons: Glutamate and Aspartate.- 6.1 Introduction.- 6.2 Anatomy and Distribution.- 6.3 Chemistry.- 6.4 Physiology of Glutamate and Aspartate.- 6.5 Pharmacology of Glutamate and Aspartate.- 6.6 Summary.- 7 Inhibitory Amino Acid Neurons: GABA and Glycine.- 7.1 Introduction.- 7.2 Anatomical Distribution of GABA Pathways in the Brain.- 7.2.1 Cerebellar Interneurons.- 7.2.2 Hippocampus.- 7.2.3 Basal Ganglia.- 7.2.4 Spinal Cord.- 7.2.5 Olfactory Bulb.- 7.2.6 Retina.- 7.2.7 Other Systems.- 7.3 Metabolism of GABA.- 7.4 Pharmacology of GABA.- 7.4.1 Administration of Precursors.- 7.4.2 Synthesis Inhibition.- 7.4.3 Storage and Release Mechanisms.- 7.4.4 Pump Inhibition.- 7.4.5 Inhibition of Metabolism.- 7.4.6 Receptor Interaction.- 7.5 Anatomical Distribution of Glycine.- 7.6 Chemistry of Glycine.- 7.7 Pharmacology and Physiology of Glycine.- 7.8 Summary.- 8 Catecholamine Neurons.- 8.1 Introduction.- 8.2 The Dopamine Neuron.- 8.2.1 Anatomy.- 8.2.2 Chemistry of Dopaminergic Neurons.- 8.2.3 Physiological Action of Dopamine and the Second Messenger Concept.- 8.2.4 Pharmacology of Dopamine.- 8.3 The Noradrenaline Neuron.- 8.3.1 Biochemistry of Noradrenergic Neurons.- 8.3.2 Physiology of Noradrenaline.- 8.3.3 Pharmacology of Noradrenaline.- 8.4 The Adrenergic Neuron.- 8.4.1 Biochemistry of Adrenergic Neurons.- 8.4.2 Physiology of Adrenergic Neurons.- 8.5 Summary.- 9 The Serotonin Neuron.- 9.1 Introduction.- 9.2 Anatomy of Serotonin Neurons.- 9.3 Metabolism of Serotonin.- 9.3.1 Tryptophan-5-Hydroxylase.- 9.3.2 5-Hydroxytryptophan Decarboxylase.- 9.3.3 Monoamine Oxidase.- 9.4 Control of Serotonin Synthesis.- 9.5 Physiological Actions of Serotonin.- 9.5.1 Serotonin and Sleep.- 9.5.2 Serotonin and Sex.- 9.5.3 Serotonin, Mood, and Mental Illness.- 9.5.4 Melatonin and Other Indoleamine Pathways.- 9.6 Pharmacology of Serotonin.- 9.6.1 Agents Toxic to Serotonin Neurons.- 9.6.2 Inhibitors of Tryptophan Hydroxylase.- 9.6.3 Inhibitors of 5-HTP Decarboxylase.- 9.6.4 Inhibitors of Monoamine Oxidase.- 9.6.5 Serotonin Pump Inhibitors.- 9.6.6 Inhibitors of Storage.- 9.6.7 Receptor Site Agonists and Antagonists.- 9.7 Summary.- 10 Promising Peptides.- 10.1 Introduction.- 10.2 Substance P.- 10.2.1 Anatomy of Substance P.- 10.2.2 Association of Substance P with Central Pathways.- 10.2.3 Chemistry and Physiology.- 10.3 Enkephalins.- 10.3.1 Anatomy of the Enkephalins.- 10.3.2 Chemistry, Physiology, and Pharmacology of the Enkephalins.- 10.4 Endorphins.- 10.5 Neurotensin.- 10.6 Carnosine.- 10.7 Angiotensin II.- 10.8 Hypophysiotropic Peptides and the Neuroendocrine System.- 10.9 Summary.- 11 Putative Transmitters and Transmitter Candidates.- 11.1 Histamine.- 11.1.1 Anatomy and Distribution of Histamine.- 11.1.2 Chemistry of Histamine.- 11.1.3 Physiology and Pharmacology of Histamine.- 11.1.4 Summary of Histamine Action.- 11.2 Amino Acids and Their Derivatives.- 11.2.1 Taurine.- 11.2.2 iV-Acetyl-L-Aspartate (NAA).- 11.2.3 Proline.- 11.2.4 Serine.- 11.3 Purine and Pyrimidine Derivatives.- 11.4 Phenethylamine Derivatives.- 11.4.1 Octopamine.- 11.4.2 p-Tyramine.- 11.5 Indoles Other Than Serotonin.- 11.5.1 N-Acetylserotonin (NAS).- 11.5.2 5-Methoxytryptamine.- 11.5.3 Tryptamine.- 11.6 Piperidine.- 11.7 Miscellaneous Transmitter Candidates.- III The Integrative Aspects of Brain Function.- 12 The Building of the Brain and Its Adaptive Capacity.- 12.1 The Building of the Brain.- 12.1.1 Introduction.- 12.1.2 The Building of the Cerebral Cortex.- 12.1.3 The Building of the Cerebellum.- 12.1.4 The Building of Brain Nuclei and the Hippocampus.- 12.2 Principles of Neuronal Recognition and Connectivity.- 12.2.1 Introduction.- 12.2.2 Chemical Sensing in the Visual Pathways of Fish, Amphibia, and Birds.- 12.2.3 Neuronal Connectivity in Mammals.- 12.2.4 Summary of Neuronal Recognition and Connectivity.- 12.3 General Conclusions.- 13 Control of Movement by the Brain.- 13.1 Introduction.- 13.2 Motor Control from the Spinal Cord and Brainstem.- 13.3 Motor Control from the Cerebral Cortex.- 13.3.1 The Motor Cortex.- 13.3.2 Cerebral Cortex Controlling Motor Cortex.- 13.3.3 Discharge of Motor Pyramidal Cells.- 13.3.4 Arrangement of Pyramidal Cells in Colonies.- 13.3.5 Alpha and Gamma Motoneurons and the Gamma Loop..- 13.3.6 Pyramidal Tract Innervation of Alpha and Gamma Motoneurons.- 13.3.7 Projection of Ia Fibers to the Cerebral Cortex.- 13.4 Motor Control by the Cerebellum.- 13.4.1 Introduction.- 13.4.2 Evidence from Cerebellar Lesions.- 13.4.3 Neuronal Structure.- 13.4.4 Neuronal Functions.- 13.4.5 Cerebrocerebellar Pathways.- 13.4.6 Cerebellospinal Connectivities.- 13.4.7 General Comments on the Cerebellum.- 13.5 Motor Control by the Basal Ganglia.- 13.5.1 Introduction.- 13.5.2 Anatomical Interconnections of the Basal Ganglia.- 13.5.3 Physiology of the Basal Ganglia.- 13.5.4 Biochemistry of the Basal Ganglia.- 13.5.5 Pharmacology of the Basal Ganglia.- 13.5.6 Summary of the Basal Ganglia.- 13.6 Synthesis of Various Neuronal Mechanisms Concerned with the Control of Voluntary Movement.- 14 Basic Behavioral Patterns.- 14.1 Introduction.- 14.2 Visceral Innervation and Feelings.- 14.3 Central Coordination of Behavior.- 14.4 Central Amines and Behavior.- 14.5 Psychoactive Drugs.- 14.5.1 Neuroleptics or Major Tranqulizers.- 14.5.2 Minor Tranquilizers or Anxiolytics.- 14.5.3 Antidepressants.- 14.5.4 Stimulants.- 14.5.5 Hallucinogenic Agents.- 14.5.6 Summary.- 14.6 The Mystery of Mental Illness.- 14.6.1 Theories of Schizophrenia.- 14.6.2 Affective Psychoses.- 14.7 Summary.- 15 Neuronal Mechanisms Involved in Learning and Memory.- 15.1 Introduction.- 15.2 Structural and Functional Changes Possibly Related to Learning and Memory.- 15.3 Motor Learning and Memory.- 15.4 The Instruction-Selection Theory of Learning in the Cerebellum.- 15.5 Cognitive Learning and Memory.- 15.6 Neural Pathways Involved in the Laying Down of Cognitive Memories According to the Instruction-Selection Theory.- 15.7 Structural Features of the Neocortex of Special Significance for the Instruction-Selection Learning Hypothesis.- 15.8 Formulation of the Instruction-Selection Hypothesis for Cognitive Learning.- 15.9 Recall of a Memory.- 15.10 Durations of Conscious Memory.- 15.11 Conclusions.- 16 Perception, Speech, and Consciousness.- 16.1 Perception.- 16.1.1 Introduction.- 16.1.2 Cutaneous Perception (Somesthesis).- 16.1.3 Visual Perception.- 16.1.4 Auditory Perception.- 16.1.5 Olfactory Perception.- 16.1.6 Emotional Coloring of Conscious Perceptions.- 16.2 The Language Centers of the Human Brain.- 16.2.1 Introduction.- 16.2.2 Aphasia.- 16.2.3 Experiments on Exposed Brains.- 16.2.4 Intracarotid Injections of Sodium Amytal.- 16.2.5 Dichotic Listening Test.- 16.2.6 Anatomical Substrates of Speech Mechanisms.- 16.3 Language and Self-Consciousness.- 16.3.1 Effects of Global Cerebral Lesions.- 16.3.2 Dominant and Minor Hemispheres.- 16.4 Relationship of Brain to Mind.- 16.4.1 Introduction.- 16.4.2 Statement of Dualist-Interactionist Hypothesis.- 16.4.3 Summary and Conclusions.- Epilogue.- References.