Molecular Neurobiology of the Olfactory System

I. Transduction and Ligand-Receptor Interactions.- 1. Olfactory Receptor Mechanisms: Odorant-Binding Protein and Adenylate Cyclase.- 1. Introduction.- 2. An Odorant-Binding Protein.- 3. Odorant Selectivity in Stimulation of Adenylate Cyclase Activity.- 4. Localization of GTP-Binding Proteins in Nasal Mucosa.- 5. Conclusions.- References.- 2. Molecular Components of Olfactory Reception and Transduction.- 1. Introduction.- 2. Olfactory Cilia: The Site of Olfactory Reception and Transduction.- 2.1. Olfactory Cilia.- 2.2. Isolated Cilia Preparations.- 3. Candidate Odorant Receptor Proteins in the Sensory Membrane.- 3.1. Expected Properties of Olfactory Receptor Proteins.- 3.2. Olfactory Receptor Candidates.- 4. Cyclic Nucleotide Enzymatic Cascade in Olfactory Transduction.- 4.1. Role of cAMP in Olfaction.- 4.2. Olfactory GTP-Binding Protein.- 4.3. Transduction Components as Odorant Receptor Probes.- 5. Possible Mechanisms of Olfactory Ion-Channel Modulation by Cyclic Nucleotides.- 5.1. Protein Phosphorylation in Olfactory Epithelium.- 5.2. Direct Ion-Channel Gating.- 6. Conclusions.- References.- 3. The Effect of Cytochrome P-450-Dependent Metabolism and Other Enzyme Activities on Olfaction.- 1. Relationships among the Fields of Inhalation Toxicology, Foreign Compound Metabolism, and Olfactory Physiology.- 2. Xenobiotic Metabolizing Enzymes Identified in the Nose and Their Function.- 2.1. Nasal Enzymes.- 2.2. Types of Metabolic Transformation.- 2.3. Capacity of Nasal Enzymes.- 2.4. Interactions of Two or More Compounds with Nasal Enzymes.- 2.5. Fate of Inhaled Materials: Are Metabolites of Odorants Present in Mucus?.- 3. Possible Effects of Nasal Metabolism on Olfaction.- 4. Research Needed to Relate Nasal Metabolism of Odorants to Olfaction.- 5. Summary and Conclusions.- References.- 4. Odorant and Autonomic Regulation of Secretion in the Olfactory Mucosa.- 1. Introduction.- 2. Organization and Characterization of the Cells in the Olfactory Mucosa.- 3. Extrinsic Innervation of the Olfactory Mucosa.- 4. Cellular Aspects of Secretion in Sustentacular Cells.- 4.1. Mucous Secretion.- 4.2. Electrolyte and Water Transport and Secretion.- 4.3. Agents That Induce Secretion from Sustentacular Cells.- 4.4. Effects of Olfactory Nerve Section.- 5. Neuropharmacological Regulation of Glandular Secretion.- 5.1. Agonist-Induced Secretion.- 5.2. Second Messengers and Modulators of Agonist-Induced Secretion…..87.- 5.3. Odorant-Induced Secretion.- 5.4. Neural Pathways of Agonist-Induced Secretion.- 6. Implications for Sensory Transduction.- 6.1. Prereceptor Events.- 6.2. Postinteractive Events.- 7. Conclusions and Research Needs.- References.- 5. Autoradiographic Localization of Drug and Neurotransmitter Receptors in the Olfactory Bulb.- 1. Introduction.- 2. Light Microscopic Receptor Autoradiography.- 3. Distribution of Receptor Types in the Olfactory Bulb.- 3.1. Cholinergic Receptors.- 3.2. Biogenic Amines.- 3.3. AminoAcids.- 3.4. Neuropeptides.- 3.5. Drug-Binding Sites.- 3.6. Miscellaneous.- 4. Conclusions.- References.- II. Molecular Biophysics And Membrane Function.- 6. Membrane Probes in the Olfactory System: Biophysical Aspects of Initial Events.- 1. Introduction.- 2. The Role of Biophysical Models within a Receptor-Mediated Model of the Initial Events in Olfaction.- 2.1. Possible Mechanisms.- 2.2. Evidence for Nonspecific Mechanisms.- 2.3. Further Experimental Evidence.- 3. Surface Potential and Single Ionic Channels.- 4. Physical Methods of Probing Initial Chemoreceptive Mechanisms.- 4.1. General Considerations.- 4.2. Photophysical Methods.- 4.3. Electron Spin Resonance.- 5. Biophysical Studies of Olfactory Epithelium.- 5.1. ESR Studies.- 5.2. Fluorescence Studies.- 5.3. Raman and Infrared Spectroscopy.- 5.4. Difference Absorption Spectrophotometry.- 5.5. Biophysical Studies Using Artificial Membranes.- 6. Summary.- References.- 7. Membrane Properties of Isolated Olfactory Receptor Neurons.- 1. Introduction.- 1.1. Basis of Interest in Olfactory Receptor Neurons.- 1.2. Obstacles to Studying Receptor Neuron Membrane Currents.- 1.3. Advantages to Patch-Clamping Isolated Receptor Neurons.- 1.4. Focus of Initial Patch-Clamp Studies.- 2. Experimental System.- 2.1. Preparation of Isolated Olfactory Receptor Neurons.- 2.2. Patch-Clamp Technique and Data Analysis.- 2.3. Perfusion System and Odorant Application.- 3. Results.- 3.1. Ion Channels in Olfactory Receptor Neurons.- 3.2. Response of Receptor Neurons to Odorants.- 4. Discussion.- 4.1. Roles of Ion Channels in Receptor Neuron Activity.- 4.2. Future Directions.- References.- 8. Voltage-Clamp Studies of the Isolated Olfactory Mucosa.- 1. Introduction.- 1.1. Chemoreception: A Property of Every Cell.- 1.2. Chapter Organization.- 2. Ion-Transporting Epithelia.- 2.1. Asymmetrical Structure: Consequences for Function.- 2.2. Special Membrane-Transport Systems.- 2.3. Paracellular Shunts.- 3. Electrophysiological Methods.- 3.1. The Short-Circuit Method (Ussing Method).- 3.2. Radioisotopes and Active Ion Transport.- 3.3. Other Methods.- 4. Theoretical Methods.- 4.1. Nonequilibrium Thermodynamics.- 4.2. Kinetic Approaches.- 5. Ion Transport and Chemoreception.- 5.1. The Sodium Taste Receptor.- 5.2. Other Ions.- 6. The Olfactory Mucosa.- 6.1. Materials and Methods.- 6.2. Active Ion Transport in the Steady State.- 6.3. The Current-Voltage Relationship.- 6.4. Odorant-Evoked Current Transients under Voltage Clamp.- 6.5. Dose-Response Relationship.- 7. Cyclic Nucleotide Modulation of Olfactory Transduction.- 7.1. cAMP Evokes an Inward Current Transient.- 7.2. cAMP Enhances Odorant-Evoked Current Transients.- 7.3. Evidence for a Stimulatory G Protein.- 7.4. cGMP Inhibits Odorant-Evoked Current Transients.- 8. Summary and Conclusions.- References.- III. Biochemical-Molecular Biological Studies.- 9. Neurotransmitter Plasticity in the Juxtaglomerular Cells of the Olfactory Bulb.- 1. Introduction.- 1.1. Overview.- 1.2. Anatomy.- 2. Alterations in Olfactory Bulb Structure and Function following Receptor Afferent Lesions.- 2.1. Changes in the Size of the Olfactory Bulb.- 2.2. Biochemical Alterations in the Olfactory Bulb.- 2.3. Immunocytochemical Observations in the Deafferented Olfactory Bulb.- 3. Development and Plasticity.- 3.1. Inductive Capacity of the Olfactory Epithelium.- 3.2. Strain Differences in Transmitter Expression in the Olfactory Bulb.- 4. Transneuronal Transport of Exogenous Materials from the Olfactory Epithelium to Brain.- 4.1. Transport of Lectins in the Olfactory System.- 4.2. Transneuronal Transport of Lectin to the Forebrain.- 4.3. Implications of Transneuronal Transport for Disease Processes.- 5. Conclusions.- References.- 10. Axoplasmic Transport in Olfactory Receptor Neurons.- 1. Introduction.- 2. The Olfactory Receptor Neuron as a Specialized Neuronal System.- 3. Transport of Low-Molecular-Weight Material.- 4. Transport of Bulk Proteins.- 4.1. Rapid Transport.- 4.2. Slow Transport.- 5. Transport of Characterized Proteins.- 6. Retrograde Transport.- 7. Organelle Movement Studied with AVEC-DIC Microscopy.- 8. Transneuronal Transport and the Spread of Virus.- 9. The Study of Axoplasmic Transport Using the Olfactory Receptor Neuron.- References.- 11. Molecular Cloning of Olfactory-Specific Gene Products.- 1. Introduction.- 2. Anatomical Organization.- 3. Biochemical Properties.- 4. Olfactory Marker Protein.- 4.1. Overview.- 4.2. Amino Acid Sequence.- 4.3. Hypothetical Approaches to the Function of Olfactory Marker Protein.- 4.4. Characterization and Cloning of the mRNA and Gene.- 4.5. Future Directions for Olfactory Marker Protein.- 5. Lesion-Induced Changes in mRNAs.- 5.1. In Vitro Translation.- 5.2. Cloning of Additional mRNAs from Nasal/Olfactory Tissue.- 6. Carnosine Synthetase.- 6.1. Overview.- 6.2. Characterization.- 6.3. Monoclonal Antibodies.- 7. Summary.- References.- IV. Development And Differentiation.- 12. Monoclonal Antibody Mapping of the Rat Olfactory Tract.- 1. Introduction.- 1.1. Scope.- 2. Strategies for Monoclonal Antibody Production.- 2.1. General Considerations.- 2.2. Monoclonal Antibodies to Adult and Embryonic Epithelium.- 2.3. Monoclonal Antibodies Raised against Membranes from Olfactory Epithelium.- 2.4. Antibodies to Carnosine Synthetase.- 3. Applications of Monoclonal Antibodies.- 3.1. Studies of the Structure of the Olfactory Epithelium.- 3.2. Monoclonal Antibody Studies of Ontogeny in the Olfactory Epithelium.- 3.3. Monoclonal Antibody Studies of Regeneration in the Olfactory Epithelium.- 3.4. Monoclonal Antibodies to Specific Proteins.- 3.5. Monoclonal Antibody Studies of Cultures of the Olfactory Epithelium.- 3.6. The Use of Monoclonal Antibodies in the Identification and Isolation of Novel Olfactory Tract Antigens.- 4. Discussion.- References.- 13. Primary Olfactory Neuron Subclasses.- 1. Introduction.- 2. Olfactory Neuron Subclasses.- 2.1. Morphological Subclasses.- 2.2. Carbohydrate Expression Subclasses.- 2.3. Other Defined Subclasses.- 3. Perspectives on Research Directions.- 3.1. Clonal Olfactory Neurons.- 3.2. Direct Approaches to Molecular Olfactory Receptors.- 3.3. Genetic Approaches.- 4. Summary.- References.- 14. Cellular Interactions in the Development of the Vertebrate Olfactory System.- 1. Introduction.- 2. Early Development and Formation of the Olfactory Placode.- 2.1. Experimental Analysis of Induction of the Olfactory Placode.- 3. Effect of Olfactory Receptor Cells on Early Formation of the Olfactory Bulb.- 4. Effect of the Olfactory Bulb on Differentiation of Receptor Cells in a Regenerating System.- 5. Effect of Olfactory Bulb on Receptor Cell Development.- 5.1. Organ Culture Method.- 5.2. Bulbar Effects on OMP Synthesis.- 5.3. Bulbar Effects on Ciliogenesis.- 5.4. Does the Bulb Exert a Tropic Effect?.- 6. Cell-Culture Studies.- 7. Summary.- References.- 15. Olfactory Tissue Interactions Studied by Intraocular Transplantation.- 1. Introduction.- 2. Organization of Olfactory Sensory Epithelial Grafts In Oculo.- 3. Indicators of Neuronal Maturation In Oculo.- 4. Factors Affecting Neuronal Maturation In Oculo.- 4.1. Epithelial Organization.- 4.2. Neurotrophic Influence of the Iris.- 4.3. Innervation of the Graft from the Iris.- 4.4. Presence of Co-transplanted Central Nervous Tissue.- 5. Factors Affecting Overall Growth of Olfactory Epithelium in Oculo.- 6. Effects of Olfactory Epithelium In Oculo on Co-transplanted CNS.- 6.1. Maturation of CNS.- 6.2. Innervation of Co-transplant by Olfactory Axons.- 6.3. Innervation of Olfactory Tissue from the CNS.- 7. Conclusions and Directions.- References.- V. Biological Relevance Of Olfactory Function.- 16. Age-Related Alterations in Olfactory Structure and Function.- 1. Introduction.- 2. Human Olfactory Perception in Later Life.- 2.1. Odor Identification.- 2.2. Odor Detection.- 2.3. Suprathreshold Odor Intensity Perception.- 2.4. Odor Discrimination.- 2.5. Odor Pleasantness.- 3. Human Olfactory Perception in Age-Related Diseases.- 3.1. Alzheimer’s Disease.- 3.2. Parkinson’s Disease.- 4. Age-Related Alterations in the Structure and Function of the Nose and the Olfactory System.- 4.1. Airflow and General Nasal Considerations.- 4.2. Olfactory Neuroepithelium.- 4.3. Olfactory Bulb.- 4.4. Higher Centers.- 5. Summary and Conclusions.- References.