Tombran-Tink / Barnstable Visual Transduction And Non-Visual Light Perception

1. Auflage 2008
ISBN: 978-1-59745-374-5
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 509 Seiten

Reihe: Ophthalmology Research

This book reveals not only how the eye evolved into an organ of vision, but also describes how molecular mechanisms of key molecules operate in the phototransduction cascade. In this groundbreaking text, experts also explain mechanisms for sensing radiation outside of the visible wavelengths. Comprehensive and penetrating, the book brings together the mechanisms of the visual transduction cascade and is an invaluable text for everyone conducting research in the visual system.

Autoren/Hrsg.

Tombran-Tink, Joyce

Barnstable, Colin J.

Inhaltsverzeichnis

1;Preface;6
2;Table of Contents;8
3;Contributors;10
4;Companion CD;12
5;Part I: Evolution of the Visual System;14
5.1;An Organ of Exquisite Perfection;15
5.1.1;Optical Path;15
5.1.2;Retinal Photoreception;17
5.1.2.1;Photoreception Optics;18
5.1.2.2;Photoreception Biochemistry;19
5.1.2.3;Membrane Voltages;20
5.1.2.4;Blind Spot;21
5.1.3;Retinal Pathways;22
5.1.3.1;Through Pathway;22
5.1.3.2;Receptive Fields;23
5.1.3.3;Lateral Pathway;23
5.1.3.4;Retinal Ganglion Cells;24
5.1.3.5;Retinal Glia;25
5.1.4;References;25
6;Part II: Photoreceptor Structure, Function, and Development;27
6.1;Development of the Foveal Specialization;29
6.1.1;Introduction;29
6.1.2;Foveal Development;32
6.1.2.1;Specification of Foveal Location;32
6.1.2.2;Formation of a Rod-Free Zone;34
6.1.2.3;Cones, Ganglion Cells, and Initial Pit Formation;36
6.1.2.4;Deep Foveal Pit Formation;38
6.1.2.5;Foveal Hypoplasia;39
6.1.3;Conclusions and Perspectives;39
6.1.4;Acknowledgments;41
6.1.5;References;41
6.2;An Update on the Regulation of Rod Photoreceptor Development;47
6.2.1;Introduction;47
6.2.2;Brief Overview of Retinal Development and Early Stages of Rod Photoreceptor Differentiation;48
6.2.3;Transcription Factors;49
6.2.3.1;Basic Helix-Loop-Helix Genes;49
6.2.3.2;QRX/Rax-L/Rx-L;53
6.2.3.3;NRL;53
6.2.3.4;Nuclear Receptors;55
6.2.3.5;Nr2E3;55
6.2.3.6;Retinoic Acid/Retinoic Acid Receptors;57
6.2.4;Extracellular Factors and Signal transduction Pathways;58
6.2.4.1;Wnt/Frizzled Pathway;58
6.2.4.2;Taurine;59
6.2.4.3;Ciliary Neurotrophic Factor/Leukemia Inhibitory Factor/Pleiotrophin/Signal Transducer and Activators of Transcription 3/SOCS;59
6.2.5;Conclusions and Future Prospects;61
6.2.6;References;62
7;Part III: The Retinal Pigment Epithelium and the Visual Cycle;77
7.1;Photoreceptor-RPE Interactions;79
7.1.1;Introduction;79
7.1.2;Retinal Adhesion;82
7.1.2.1;Physiology of Retinal Adhesion;82
7.1.2.2;Molecular Mechanisms of Retinal Adhesion;82
7.1.2.3;Significance of Retinal Adhesion for Retinal Function;85
7.1.3;Photoreceptor Outer Segment Renewal;86
7.1.3.1;Physiology of Outer Segment Disk Assembly and Disk Shedding;86
7.1.3.2;Physiology of RPE Engulfment of Shed Outer Segment Fragments;87
7.1.3.3;Molecular Mechanisms of Shedding and RPE Phagocytosis;88
7.1.3.4;Significance of Photoreceptor Outer Segment Renewal for Retinal Function;93
7.1.4;Perspective;93
7.1.5;Acknowledgments;93
7.1.6;References;94
7.2;Molecular Biology of IRBP and Its Role in the Visual Cycle;99
7.2.1;Introduction;99
7.2.2;IRBP Protein Studies;100
7.2.3;IRBP Null Mice;100
7.2.4;IRBP Induces Experimental Autoimmune Uveitis;101
7.2.5;IRBP Expression During Development;101
7.2.6;Variability in IRBP Expression;103
7.2.7; Molecular Biology of IRBP;103
7.2.8;IRBP Genomic Cloning;104
7.2.9;Evolution of IRBP;104
7.2.10;Importance of the STUDY of the Control of Gene Expression;108
7.2.11;Identification of DNA cis-Acting Controlling Elements: In Vitro and In Vivo Experiments;110
7.2.12;Transcription Factors and their Role in the Control of IRBP Expression;112
7.2.12.1;Rx/rax Transcription Factor;112
7.2.12.2;NrL Transcription Factor;114
7.2.12.3;Crx Transcription Factor;115
7.2.12.4;OTX2 Transcription Factor;116
7.2.13;Transgenic Mice;118
7.2.14;Repressors of IRBP Gene Expression;118
7.2.14.1;KLF15;118
7.2.14.2;MOK2;119
7.2.14.3;Chx10;119
7.2.15;Summary and Conjecture;126
7.2.16;Acknowledgments;127
7.2.17;References;127
8;Part IV: Visual Signaling in the Outer Retina;135
8.1;Regulation of Photoresponses by Phosphorylation;137
8.1.1;Introduction;137
8.1.2;Inactivation of Photoactivated Rhodopsin vy Rhodopsin Kinase;139
8.1.3;Cone-Specific Kinase, GRK7;142
8.1.4;Protein Kinase C;142
8.1.5;Cyclic Adenosine Monophosphate-Dependentprotein Kinase, PKA;144
8.1.6;Cyclin-Dependent Kinase;144
8.1.7;Tyrosine Kinases;144
8.1.8;Mitogen-Activated Protein Kinase Andcalmodulin-Dependent Protein Kinase II;145
8.1.9;Protein Phosphatases;145
8.1.10;Conclusion;145
8.1.11;References;146
8.2;The cGMP Signaling Pathway in Retinal Photoreceptors and the Central Role of Photoreceptor Phosphodiesterase (PDE6);153
8.2.1;Overview of Cyclic Guanosine Monophosphatesignaling Pathways;153
8.2.1.1;Regulation of Intracellular cGMP Levels in Photoreceptor Cells;154
8.2.1.2;Downstream Targets of cGMP Action in Photoreceptor Cells;154
8.2.1.3;cGMP-Dependent Protein Kinase;154
8.2.1.4;Cyclic Nucleotide-Gated Ion Channels;155
8.2.1.5;PDE6 Is a High-Affinity cGMP-Binding Protein;155
8.2.2;The Cellular Context of cGMP Signaling In Verteb Rateretinal Photoreceptors;155
8.2.2.1;Compartmentation of cGMP Signaling in Photoreceptor Outer Segments;155
8.2.2.2;Physiology of the Photoreceptor Response to Light;156
8.2.2.3;Biochemical Cascade of Visual Excitation;156
8.2.2.4;Central Components of the cGMP Signaling Pathway;157
8.2.2.5;Termination and Adaptation of the Light Response;158
8.2.2.6;Deactivation of Rhodopsin;159
8.2.2.7;Deactivation of Transducin;159
8.2.2.8;Deactivation of PDE6;159
8.2.2.9;Activation of GC;160
8.2.2.10;Regulation of the CNG Ion Channel;160
8.2.3;Photoreceptor PDE (PDE6) Structure and Function;160
8.2.3.1;The Cyclic Nucleotide Phosphodiesterase Superfamily;160
8.2.3.2;Subunit Composition of Rod and Cone PDE6 Holoenzyme;161
8.2.3.3;Catalytic Subunit;161
8.2.3.4;Regulatory GAF Domain;161
8.2.3.5;Catalytic Domain;163
8.2.3.6;C-Terminal Prenylation;163
8.2.3.7;Inhibitory gamma-Subunit;164
8.2.3.8;PDE6 Has Evolved to Meet the Special Demands of the Central Effector of Visual Transduction;165
8.2.4;PDE6 Regulation;166
8.2.4.1;Transducin Activation of Rod PDE6 During Visual Excitation;166
8.2.4.2;Functions of the Regulatory cGMP-Binding GAF Domains of PDE6;166
8.2.4.3;Potential PDE6 Regulatory Binding Proteins;169
8.2.4.4;Glutamic Acid-Rich Protein 2;169
8.2.4.5;17-kDa Prenyl-Binding Protein (PDEdelta);170
8.2.5;Conclusions;170
8.2.6;Acknowledgments;171
8.2.7;References;171
8.3;Rhodopsin Structure, Function, and Involvement in Retinitis Pigmentosa;183
8.3.1;Introduction;183
8.3.2;Historical Perspective;186
8.3.3;Rhodopsin as the Prototypical G Protein-Coupled Receptor;186
8.3.4;Rhodopsin, Localization, and Signaling;187
8.3.5;Dark State and Activation;189
8.3.6;Structural Analysis;191
8.3.6.1;Electron Cryomicroscopy and Crystal Structure;191
8.3.6.2;Nuclear Magnetic Resonance;192
8.3.6.3;Cysteine Mutagenesis and Electron Paramagnetic Resonance;192
8.3.6.4;Other Approaches;192
8.3.7;Retinitis Pigmentosa;194
8.3.7.1;Transmembrane RP Rhodopsin Mutants;195
8.3.7.2;Cytoplasmic RP Rhodopsin Mutants;198
8.3.7.3;Intradiskal RP Rhodopsin Mutants;198
8.3.8;Implications of Receptor Misfolding;199
8.3.9;Nongenetic Contributions to RP;200
8.3.10;Conclusion;201
8.3.11;References;201
8.4;Multiple Signaling Pathways Govern Calcium Homeostasis in Photoreceptor Inner Segments;209
8.4.1;Introduction;209
8.4.2;Overview of Ca2+ Regulation in the Inner Segment;212
8.4.3;Voltage-Operated Calcium Channels Play a Central Role in Inner Segment Calcium Regulation;214
8.4.3.1;Ca2+ Channels in Rods and Cones;217
8.4.4;Neurotransmission from Rods and Cones to Second-Order Retinal Neurons;218
8.4.5;Photoreceptor Malfunction and Degeneration;220
8.4.5.1;Therapeutic Strategies;223
8.4.6;Development;224
8.4.7;Acknowledgments;224
8.4.8;References;225
8.5;The Transduction Channels of Rod and Cone Photoreceptors;237
8.5.1;The Transduction Channels of Rod and Cone Photoreceptors;237
8.5.2;The Role of CNG Channels in Photoreceptor Physiology;238
8.5.2.1;The Activation Phase of the Light Response;239
8.5.2.2;Recovery After a Light Stimulus and Adaptation to Continuous Illumination;240
8.5.2.3;CNG Channels in the Synaptic Transmission of Cone Photoreceptors;240
8.5.3;The Molecular Composition of CNG Channels;241
8.5.4;The Basic Activation Properties of CNG Channels;242
8.5.5;Transmembrane Topology and Functional Domains;243
8.5.5.1;The Cyclic-Nucleotide-Binding Domain;243
8.5.5.2;The Amino Terminal Domain and Modulation by Calmodulin;244
8.5.5.3;The P Region;244
8.5.5.4;The GARP Domain of CNGB1;246
8.5.6;CNG Channels are Components of Larger Protein Complexes;246
8.5.7;Modulation by Phosphorylation and All-trans Retinal;247
8.5.8;Synthesis, Maturation, and Targeting of CNG Channels;248
8.5.9;Visual Dysfunction Caused by Mutant CNG Channel Genes;249
8.5.10;References;251
8.5.11;Appendix;255
8.5.11.1;Visual Dysfunction Caused by Mutant CNG Channel Genes;255
8.5.11.2;Mutations in CNGA1 and CNGB1 Associated with Retinitis Pigmentosa;256
8.5.11.3;Mutations in CNGA3 and CNGB3 Associated with Cone Dysfunction;257
8.5.11.4;References;259
8.6;Rhodopsins in Drosophila Color Vision;263
8.6.1;Introduction;263
8.6.2;Anatomy and Molecular Aspects of Color-Sensitive Opsins in the Drosophila Eye;264
8.6.2.1;Structure of the Drosophila Eye: Ommatidia, Photoreceptors, and Rhodopsins;264
8.6.2.2;Molecular Genetics and Evolution of Rh5 and Rh6;265
8.6.3;Development and Patterning of Rhodopsins for Drosophila Color Vision;267
8.6.3.1;Mutually Exclusive Rhodopsin Expression;267
8.6.3.2;Transcription Factors Specify Outer from Inner Photoreceptors and Distinguish R7 from R8;269
8.6.3.3;A Stochastic Decision Induces Rhodopsins in R7 Photoreceptor;270
8.6.3.4;A Bistable Feedback Loop Specifies R8 Photoreceptor Subtype and Expression of Rh5 and Rh6;270
8.6.4;Comparison Between Mammalian and Drosophila Color Vision Rhodopsins;272
8.6.4.1;Human Color-Sensitive Opsins;272
8.6.4.2;Photoreceptor and Rhodopsin Specification in Flies and Mammals: Parallel Themes;273
8.6.4.3;Photoreceptor and Rhodopsin Specification in Flies and Mammals: Different Mechanisms;274
8.6.5;Conclusion;274
8.6.6;References;275
8.7;INAD Signaling Complex of Drosophila Photoreceptors;279
8.7.1;Introduction;279
8.7.2;Comparison of Vertebrate and Drosophila Phototransduction Cascades;280
8.7.3;Identification of the INAD Signaling Complex;281
8.7.4;Structure of the INAD Signaling Complex and Binding Specificity;283
8.7.5;Anchoring of the INAD Signaling Complex to the Microvillar Membrane;286
8.7.6;Function of the INAD Signaling Complex;287
8.7.7;Information Transfer From Rhodopsin to the Signaling Complex BY the Visual G Protein;288
8.7.8;Signaling Complexes in Vertebrate Photoreceptor Cells;290
8.7.9;Acknowledgments;292
8.7.10;References;292
9;Part V: Visual Processing in the Inner Retina;297
9.1;Visual Signal Processing in the Inner Retina;299
9.1.1;Introduction;299
9.1.2;Visual Information is First Processed in the OPL;300
9.1.3;Bipolar Cells form Parallel Pathways and Provide Excitatory Input to the IPL;300
9.1.4;Functional Stratification of the IPL;302
9.1.4.1;ON and OFF Response Stratification;302
9.1.4.2;Sustained and Transient Response Stratification;303
9.1.5;Synaptic Mechanisms Shape Excitatory Signals in the IPL;303
9.1.5.1;Glutamate Release Is Tonic and Graded;303
9.1.5.2;Transporters Terminate Excitatory Signaling to Ganglion Cells;304
9.1.5.3;Postsynaptic Glutamate Receptor Properties Shape Ganglion Cell Excitation;304
9.1.5.4;Modulating Glutamate Release Shapes Excitatory Responses;305
9.1.5.5;Amacrine Cells Mediate Inhibition in the IPL;305
9.1.6;Presynaptic Inhibition;306
9.1.6.1;Asymmetric Presynaptic Inhibition;306
9.1.6.2;Presynaptic Inhibition Is Filtered by GABA Receptor Properties;307
9.1.6.3;Presynaptic Inhibition May Be Shaped by Transmitter Release Differences;307
9.1.6.4;Glycine, the Other Inhibitory Transmitter;310
9.1.6.5;Lateral Versus Vertical Inhibitory Pathways in the IPL: The Story of Two Inhibitory Neurotransmitters;310
9.1.6.6;Parallel Ganglion Cell Output Pathways;311
9.1.6.7;Ganglion Cells Encode Color Information;311
9.1.6.8;Directional-Selective Ganglion Cells;312
9.1.6.9;Intrinsically Photosensitive Ganglion Cells;312
9.1.7;Conclusions;312
9.1.8;References;313
10;Part VI: Color Vision and Adaptive Processes;317
10.1;Human Cone Spectral Sensitivities and Color Vision Deficiencies;319
10.1.1;Introduction;319
10.1.1.1;Overview;319
10.1.1.2;Transduction;319
10.1.1.3;Univariance, Monochromacy, Dichromacy, and Trichromacy;320
10.1.1.4;Trichromacy and Color-Matching Functions;321
10.1.2;Cone Spectral Sensitivities;322
10.1.2.1;Introduction;322
10.1.2.2;Cone Spectral Sensitivity Measurements;322
10.1.2.3;From Cone Spectral Sensitivities to Color-Matching Functions;325
10.1.3;Other Factors That Influence Spectral Sensitivity;325
10.1.3.1;Lens Pigment;325
10.1.3.2;Macular Pigment;326
10.1.3.3;Photopigment Optical Density;326
10.1.3.4;Changes with Eccentricity;326
10.1.4;Congenital Color Vision Deficiencies;326
10.1.4.1;Protan and Deutan Defects;327
10.1.4.1.1;Protanopia and Deuteranopia;327
10.1.4.1.2;Photopigment Variability and Protanomaly and Deuteranomaly;328
10.1.4.2;Tritanopia;330
10.1.4.3;Monochromacies;331
10.1.4.3.1;Cone Monochromacies;331
10.1.4.3.2;Rod Monochromacy;332
10.1.5;Conclusions;333
10.1.6;Acknowledgment;333
10.1.7;References;333
10.2;Luminous Efficiency Functions;341
10.2.1;Introduction;341
10.2.1.1;The Need for Luminous Efficiency;341
10.2.1.2;Psychophysical Measures of Luminous Efficiency;344
10.2.1.3;Factors that Influence Luminous Efficiency;344
10.2.2;Scotopic (Rod) Luminous Efficiency Function;345
10.2.2.1;Introduction;345
10.2.2.2;Univariance;345
10.2.2.3;International Standard;346
10.2.3;Photopic (Cone) Luminous Efficiency Function;346
10.2.3.1;Introduction;346
10.2.3.2;International Standards;347
10.2.3.2.1;Additive Functions for 2degree Viewing Fields;347
10.2.3.2.2;Additive Functions for 10degree Viewing Fields;348
10.2.3.2.3;Other Photopic (Nonadditive) Luminous Efficiency Functions;350
10.2.4;Mesopic (Rod-Cone) Luminous Efficiency Functions;351
10.2.4.1;Introduction;351
10.2.4.2;Models of Mesopic Luminous Efficiency;351
10.2.4.3;International Standard;352
10.2.5;Individual Differences Influencing Luminous Efficiency;352
10.2.5.1;Attenuation of Spectral Light by the Lens and Other Ocular Media;352
10.2.5.2;Attenuation of Spectral Light by the Macular Pigment;353
10.2.5.3;Optical Densities of the Photopigments;354
10.2.5.4;Relative Numbers of L and M Cones;355
10.2.5.5;Cone Pigment Polymorphisms;355
10.2.5.6;Directional Sensitivity;356
10.2.5.7;Variations in the Contribution of Chromatic Channels;356
10.2.6;Conclusions;356
10.2.7;References;357
10.3;Cone Pigments and Vision in the Mouse;365
10.3.1;Introduction;365
10.3.2;Prevalence and Spatial Distribution of Mouse Cones;365
10.3.2.1;Mouse Strain Variations;366
10.3.3;Mouse Cone Pigments;367
10.3.3.1;Cone Pigment Spectra;367
10.3.3.2;Evolution and Spectral Tuning of Mouse Cone Pigments;367
10.3.3.3;Regional Distribution of Mouse Cone Pigments;368
10.3.3.4;Expression of Mouse Cone Pigments;371
10.3.4;Cone Signal Pathways in the Mouse Retina;371
10.3.5;Cone-Based Vision in Mice;373
10.3.5.1;Assessment Techniques;373
10.3.5.2;Spectral Sensitivity;375
10.3.5.3;Spatial and Temporal Sensitivity;376
10.3.5.4;Color Vision;377
10.3.6;Alterations in Mouse Vision Consequent to Genetic Manipulations;379
10.3.6.1;Targeted Deletions of Rods or Cones;379
10.3.6.2;Addition of New Cone Pigments;380
10.3.7;Mouse and Human Cone Vision;381
10.3.8;Acknowledgment;382
10.3.9;References;382
10.4;Multifocal Oscillatory Potentials of the Human Retina;387
10.4.1;Introduction;387
10.4.2;Recording Techniques;387
10.4.3;Underlying Mechanisms;388
10.4.4;The Influence of age and Gender;391
10.4.5;Disease-Related Changes;392
10.4.5.1;Origins of Single Potentials;392
10.4.5.1.1;Dichromats;392
10.4.5.1.2;Congenital Stationary Night Blindness;394
10.4.5.2;Topographical Alterations;394
10.4.5.2.1;Diabetes;395
10.4.5.2.2;Retinal Vessel Occlusion;397
10.4.5.2.3;Glaucoma;397
10.4.5.2.4;General Alterations;397
10.4.5.2.5;Vigabatrin Treatment;398
10.4.6;Conclusion;399
10.4.7;References;399
11;Part VII: Aging and Vision;401
11.1;The Aging of the Retina;403
11.1.1;Introduction;403
11.1.2;Morphological Alterations;404
11.1.2.1;Neural Changes;404
11.1.2.2;Retinal Pigment Epithelium and Lipofuscin Formation;405
11.1.2.3;Bruch’s Membrane and Choroid;406
11.1.3;Retinal Function Changes;407
11.1.4;Age-Related Macular Disease;407
11.1.5;Conclusions;409
11.1.6;References;410
11.2;Aging of the Retinal Pigment Epithelium;415
11.2.1;Introduction;415
11.2.2;Aging Changes In the Fundus;416
11.2.3;Age-Related Changes In RPE Morphology;416
11.2.3.1;Melanosomes;419
11.2.3.2;Lipofuscin;419
11.2.3.3;Pigment Complexes;419
11.2.3.4;Mitochondria;420
11.2.3.5;Bruch’s Membrane;420
11.2.4;Functional Consequences of RPE Cell Aging;420
11.2.4.1;Phagocytic Load;420
11.2.4.2;The Effect of Lipofuscin on the RPE;420
11.2.4.3;Melanosomes;422
11.2.4.4;Antioxidant Capacity of the RPE;422
11.2.4.5;Lysosomal Enzyme Activity;422
11.2.4.6;Mitochondrial Damage in the RPE;423
11.2.4.7;Bruch’s Membrane Aging;424
11.2.5;Oxidative Stress and RPE Aging;424
11.2.6;The Relationship Between Aging and Retinal Pathologies;427
11.2.7;Summary and Conclusions;428
11.2.8;References;428
11.3;Visual Transduction and Age-Related Changes in Lipofuscin;433
11.3.1;Introduction: What is Lipofuscin?;433
11.3.2;Lipofuscin of the Retinal Pigment Epithelium;434
11.3.2.1;Composition of RPE Lipofuscin;435
11.3.2.2;Fluorescence Properties of RPE Lipofuscin;437
11.3.2.3;A2E as a Marker of Lipofuscin Accumulation;438
11.3.3;Factors Affecting Accumulation of RPE Lipofuscin;438
11.3.3.1;Phagocytosis and Autophagy;439
11.3.3.2;Role of Lysosomal Degradation;440
11.3.3.3;Role of Oxidative Stress;440
11.3.3.4;Role of Phototransduction in Accumulation of RPE Lipofuscin;441
11.3.3.4.1;Transient Buildup of All-trans Retinal in Photoreceptor Outer Segments as a Critical Factor for Lipofuscin Formation;443
11.3.3.4.2;Inhibition of the Retinoid Cycle Inhibits Lipofuscin Accumulation;446
11.3.3.5;Role of Exposure of the Retina to Light;448
11.3.3.6;Other Factors Contributing to Accelerated Accumulation of RPE Lipofuscin;449
11.3.3.7;A Hypothetical Scenario of Biogenesis of RPE Lipofuscin;451
11.3.4;Effects of Lipofuscin on RPE Function and Viability;454
11.3.4.1;Photoreactivity of RPE Lipofuscin;454
11.3.4.2;Toxicity of RPE Lipofuscin;457
11.3.4.3;Effects of Lipofuscin Components and Oxidative Stress in the RPE on Proinflammatory and Angiogenic Signaling;459
11.3.5;Approaches to Diminish Lipofuscin Accumulation or Lipofuscin-Induced Damage;460
11.3.6;Conclusions;462
11.3.7;References;463
12;Part VIII: Nonphotoreceptor Light Detection and Circadian Rhythms;475
12.1;A Nonspecific System Provides Nonphotic Information for the Biological Clock;477
12.1.1;Introduction;477
12.1.2;Nonphotic Information;478
12.1.3;Nonspecific Systems;479
12.1.3.1;Ascending Reticular-Activating System;479
12.1.3.2;Orexin/Hypocretin Projection;480
12.1.4;Intergeniculate Leaflet of the Thalamus;483
12.1.4.1;Anatomy;483
12.1.4.2;The Pharmacology of the IGL;484
12.1.4.3;Chronobiology;485
12.1.4.4;The Electrophysiology of the IGL;485
12.1.4.5;IGL as an Integrator of Photic and Nonphotic Information;487
12.1.5;Conclusions;487
12.1.6;References;488
12.2;The Circadian Clock: Physiology, Genes, and Disease;493
12.2.1;Introduction;493
12.2.1.1;Circadian Rhythms in Physiology and Behavior;493
12.2.1.2;Circadian Rhythms in Visual Function;494
12.2.2;Entrainment;495
12.2.3;Anatomy;496
12.2.3.1;The Suprachiasmatic Nucleus;496
12.2.3.2;Inputs to the SCN;498
12.2.3.3;Peripheral Oscillators;499
12.2.3.3.1;A Clock in the Eye;499
12.2.3.3.2;Oscillators Outside the Nervous System;499
12.2.4;Clock Genes;500
12.2.5;Human Implications;504
12.2.6;Summary;504
12.2.7;References;504
13;Index;513