Table Of Content

From Photon to Neuron Bookcover: [Confocalfluorescencemicrograph.]Thevertebrateretinaismadeupoflayersofdifferent cell types. To create this image, the rod photoreceptor cells of a mouse (in the outer nuclear layer, far right) were labeled in red. Moving leftward, the next layers constitute the inner nuclear layer (center): bipolar cells were labeled in green; the amacrine and horizontal cells were labeled in blue. Nextcomestheinnerplexiformlayer(green filaments),includinginterconnections,andfinallyalayer containing ganglion cell bodies (far left, blue). These cell types and their functions are described in Chapter 11. The magnification is such that the cell diameters are about 5µm. Ingreaterdetail,theexperimentersgeneratedDNAplasmidsthatdrovefluorescentproteinexpression, either enhanced GFP or a red emitter named mCherry, in bipolar cells or rods respectively. They also used short DNA segments (enhancers), that made the fluorescent proteins express in a cell type-specific manner (similarly to methods discussed in Chapter 2). Other cell types in the inner nuclear layer (INL, center) were tagged with fluorescent antibodies. (Yet other cell types that make uptheretinawerenotlabeled,includingtheconephotoreceptorcellsandthemajorityofMu¨llerglia cells. Rodoutersegmentsareonlyfaintlyvisibleonfar right becausemostofthefluorescentprotein remained confined to the inner segment and cell body.) [CourtesyofDr.SuiWangandDr.Constance Cepko;seealsoWangetal.,2014.] The basic structural organization of the retina shown here is conserved across vertebrates and is responsiblefordetecting,preprocessing,andconveyingallofthedifferentkindsofvisualinformation about the outside world to the brain. This image also demonstrates that specific cell types can be genetically manipulated in vivo, with potential applications to therapy and basic science. For example, an optogenetic protein can be introducedonlyinbipolarcells,renderingthemphotosensitive,anapproachbeingtakentocompensate for loss of photoreceptors in disease (see Section 11.4.3). Inset: Fragment from Albert Einstein’s 1905 article introducing the photon concept. The formula appears in the text, in modern notation, as Equation 1.6 (page 34). [FromEinstein,1905.] Facing page: Protein structures shown in Figure 10.13 (page 338). Vesicle: A1 - synaptobrevin; A2 - synaptotagmin; A3 - Rab; A4 - synaptophysin; A5 - vGlut; A6 - vesicular ATPase. Presynaptic cytoplasm:B1-dystrophin;B2-actin;B3-NSF;B4-munc13(inactive);B5-GDI(guaninenucleotide dissociation inhibitor); B6 - munc13/munc18; B7 - bassoon; B8 - RIM, CAST, etc.; B9 - ribeye; B10 - PRA1 (connection between bassoon and Rab); B11 - speculative bridging protein. Presynaptic membrane: C1 - EAAT (excitatory amino acid transporter); C2 - SNAP25; C3 - syntaxin; C4 - sidekick/DSCAM(speculative);C5-PSD-95;C6-voltage-gatedcalciumchannel;C7-dystroglycan; C8 - src; C9 - LAR (receptor-type tyrosine-protein phosphatase); C10 - sodium/potassium ATPase. Cleft: D1 - laminin; D2 - pikachurin. Postsynaptic membrane: E1 - iGluR; E2 - mGluR; E3 - G protein; E4 - adenyate cyclase; E5 - TRPM1; E6 - nyctalopin; E7 - PSD-95/MAGI (speculative); E8 - Fyn; E9 - potassium channel; E10 - ErbB (as a generic receptor tyrosine kinase). Postsynaptic cytoplasm: F1 - GKAP; F2 - SHANK; F3 - Homer. [ArtbyDavidSGoodsell.] From Photon to Neuron Light, Imaging, Vision B2 B1 C2 C1 B3 B4 B6 A1 C4 A2 A3 C2 B5 C7 C6 C5 C3 D2 C3 A4 C8 B10 D1 B8 B11 B8 B7 A5 B8 E9 C9 F2 B8 E8 F1 B8 B9 E7 C10 F3 E5 E6 E3 E4 E3 E2 E1 E10 A6 Philip Nelson With the assistance of Sarina Bromberg, Ann M. Hermundstad, and Jesse M. Kinder Princeton University Press Princeton and Oxford Copyright c 2017 by Philip C. Nelson. (cid:13) Published by Princeton University Press, 41 William Street, Princeton, New Jersey 08540 In the United Kingdom: Princeton University Press, 6 Oxford Street, Woodstock, Oxfordshire OX201TR press.princeton.edu Cover: The retina is responsible for detecting and preprocessing visual information about the outside world and conveying that information to the brain. [Courtesy Constance Cepko, Harvard Medical School Department of Genetics and Ophthalmology and Howard Hughes Medical Institute, and Sui Wang, Stanford Medical School Department of Ophthalmology.] The inset shows a fragment from Albert Einstein’s 1905 article introducing the photon concept. All Rights Reserved ISBN 978-0-691-17518-8 ISBN (pbk.) 978-0-691-17519-5 British Library Cataloging-in-Publication Data is available. Publication of this book has been aided by the United States National Science Foundation. This book was composed using the LATEX typesetting system. The publisher would like to acknowledge the author of this volume for providing the print-ready files from which this book was printed. Printed on acid-free paper. ∞ Printed in the United States of America. 1 3 5 7 9 10 8 6 4 2 For Scott Weinstein and William Berner And yet, protest it if we will, Some corner of the mind retains The medieval man, who still Keeps watch upon those starry skeins And drives us out of doors at night To gaze at anagrams of light. — Adrienne Rich Brief contents Prologue: Preliminaries 1 PART I Doorways of Light Chapter 1 What Is Light? 23 Chapter 2 Photons and Life 61 Chapter 3 Color Vision 107 Chapter 4 How Photons Know Where to Go 145 Chapter 5 Optical Phenomena and Life 180 PART II Human and Superhuman Vision Chapter 6 Direct Image Formation 209 Chapter 7 Imaging as Inference 247 Chapter 8 Imaging by X-Ray Diffraction 272 Chapter 9 Vision in Dim Light 290 Chapter 10 The Mechanism of Visual Transduction 318 Chapter 11 The First Synapse and Beyond 352 PART III Advanced Topics Chapter 12 Electrons, Photons, and the Feynman Principle 381 Chapter 13 Field Quantization, Polarization, and the Orientation of a Single Molecule 398 vii viii Chapter 14 Quantum-Mechanical Theory of FRET 415 Epilogue 423 Appendix A Global List of Symbols 431 Appendix B Units and Dimensional Analysis 439 Appendix C Numerical Values 446 Appendix D Complex Numbers 449 Contents Index Notation Detailed contents Web resources xx To the student xxi To the instructor xxv Prologue: Preliminaries 1 0.1 Signpost: Uncertainty 1 0.2 Discrete Probability Distributions 2 0.2.1 Aprobabilitydistributionsummarizesourknowledgeaboutanuncertainsituation 2 0.2.2 Conditionalprobabilityquantifiesthedegreetowhicheventsarecorrelated 4 0.2.3 Arandomvariablecanbepartiallydescribedbyitsexpectationandvariance 4 0.2.4 Jointdistributions 6 0.2.5 Someexplicitdiscretedistributions 7 0.3 Dimensional Analysis 9 0.4 Continuous Probability Distributions 10 0.4.1 Probabilitydensityfunctions 10 0.4.2 Someexplicitcontinuousdistributions 12 0.5 More Properties of, and Operations on, Probability Distributions 14 0.5.1 Transformationofaprobabilitydensityfunction 15 0.5.2 Thesamplemeanofmanyindependent,identicallydistributedrandomvariableshaslowervariancethan anyoneofitsconstituents 15 0.5.3 CountdataaretypicallyPoissondistributed 16 0.5.4 Thedifferenceoftwonoisyquantitiescanhavegreaterrelativestandarddeviationthaneitherby itself 16 0.5.5 Theconvolutionoftwodistributionsdescribesthesumoftheirrandomvariables 16 0.6 Thermal Randomness 17 Big Picture 17 Key Formulas 18 Problems 19 PART I Doorways of Light Chapter 1 What Is Light? 23 1.1 Signpost: Photons 23 1.2 Light Before 1905 24 1.2.1 Basiclightphenomena 25 1.2.2 Lightdisplayswavelikebehaviorinmanysituations 25 1.3 Light Is Lumpy 26 1.3.1 Thediscreteaspectoflightismostapparentatextremelylowintensity 27 1.3.2 Thephotoelectriceffect 30 ix