Note: Intro -- Dedication -- Acoustical Society of America -- Series Preface -- Preface 1992 -- Volume Preface -- Contents -- Contributors -- Chapter 1: Auditory System Development: A Tribute to Edwin W Rubel -- 1.1 Contributions to Science -- 1.1.1 Early Career -- 1.1.2 Auditory Brainstem -- 1.1.3 Dendritic Regulation -- 1.1.4 Cochlea Frequency-Place Map -- 1.1.5 Hair Cell Regeneration -- 1.1.6 Prevention of Hearing Loss -- 1.1.7 Scientific Community -- 1.2 Overview of Chapters -- 1.2.1 Development of the Mechanosensory Periphery -- 1.2.2 Auditory Brainstem Development -- 1.2.3 Development of Auditory Perception -- 1.3 Conclusions -- References -- Chapter 2: Development and Regeneration of Sensory Hair Cells -- 2.1 Introduction -- 2.2 Hair Cell Development -- 2.2.1 Sensorineural Development in the Inner Ear -- 2.2.2 Initial Differentiation of Hair Cells -- 2.2.2.1 Atoh1 Is Necessary and Sufficient for Hair Cell Formation -- 2.2.2.2 Regulation of Hair Cell and Supporting Cell Fates Through Notch Signaling -- 2.2.2.3 Onset of Atoh1 Expression -- 2.2.3 Hair Cell Development Beyond Atoh1 -- 2.2.4 Summary of Development -- 2.3 Hair Cell Regeneration -- 2.3.1 Overview -- 2.3.2 Hair Cell Injury, Death, and Repair -- 2.3.3 Hair Cell Regeneration in Nonmammalian Vertebrates -- 2.3.3.1 Hair Cell Progenitors in Nonmammalian Vertebrates: Identity and Behavior -- 2.3.3.2 Morphological and Functional Maturation of Regenerated Hair Cells in Nonmammalian Vertebrates -- 2.3.4 Hair Cell Regeneration in Mammals: The Cochlea -- 2.3.5 Hair Cell Regeneration in Mammals: Vestibular Organs -- 2.3.6 Molecular Control of Hair Cell Regeneration in Nonmammals -- 2.3.6.1 Regulators of Supporting Cell Division in Nonmammals -- 2.3.6.2 Regulators of Hair Cell Differentiation in Nonmammals -- 2.3.6.3 Factors Limiting Hair Cell Regeneration in Mammals. , 2.3.7 Future Considerations for Hair Cell Regeneration -- 2.3.8 Summary -- References -- Chapter 3: The Molecular and Cellular Mechanisms of Zebrafish Lateral Line Development -- 3.1 Introduction -- 3.2 Early Development of the Lateral Line -- 3.2.1 Formation of Lateral Line Placodes -- 3.2.2 Molecular Mechanisms of Lateral Line Placode Formation -- 3.3 Development of the Posterior Lateral Line System -- 3.3.1 Primordia Migration Forms the Zebrafish Lateral Line -- 3.3.2 Organization of the pLLP -- 3.3.3 Progenitor Cell Identity and Maintenance -- 3.3.4 FGF Signaling and Proto-NM Formation -- 3.3.5 Regulation of NM Deposition and Spacing -- 3.3.6 Directional Migration -- 3.3.7 Hair Cell Specification and Differentiation -- 3.4 Mechanosensory Hair Cells of the Lateral Line -- 3.4.1 Development and Physiology -- 3.5 Posterior Lateral Line Innervation -- 3.5.1 Pioneer Axon Extension and Pathfinding -- 3.5.2 Peripheral Topography and Central Somatotopy of the pLL -- 3.5.3 The Unexplored Role of Efferents -- 3.5.4 Innervation of Planar Polarized Hair Cells -- 3.6 Postembryonic Lateral Line Development in the Zebrafish -- 3.7 Summary -- References -- Chapter 4: Glutamate Signaling in the Auditory Brainstem -- 4.1 Introduction to Glutamate Signaling -- 4.2 Synaptic Excitation -- 4.2.1 Presynaptic Release -- 4.2.2 Ionotropic Glutamate Receptors -- 4.2.3 Metabotropic Glutamate Receptors -- 4.2.4 Calcium Signaling -- 4.3 Development of Synaptic Excitation -- 4.3.1 Morphology and Physiology -- 4.3.2 Cotransmission: Excitation Mediated by Inhibitory Neurotransmitters -- 4.4 Activity-Dependent Regulation of Glutamate Signaling -- 4.4.1 Short-Term Synaptic Plasticity -- 4.4.2 Long-Term Synaptic Plasticity -- 4.4.3 Pathophysiology and Glutamate Signaling -- 4.5 Neuromodulation of Glutamate Signaling -- 4.5.1 Homosynaptic Modulation. , 4.5.2 Heterosynaptic Modulation -- 4.6 Summary -- References -- Chapter 5: Development and Function of Inhibitory Circuitry in the Avian Auditory Brainstem -- 5.1 Introduction: The Elegant Circuit -- 5.1.1 The Excitatory Pathways of the ITD Processing Circuit -- 5.1.2 Sources of Inhibition -- 5.2 Embryonic Origins and Development of SON Innervation -- 5.3 Inhibitory Synaptic Physiology: Slow, Depolarizing, and Potent -- 5.3.1 GABAergic Input to NM and NL Is Depolarizing -- 5.3.2 An Unexpected Role for Glycine in the Avian Auditory Brainstem -- 5.3.3 A Role for Phase-Locked Inhibition in Birds? -- 5.4 Binaural Processing in Balance: The SON Circuit from a Systems View -- 5.5 Summary -- References -- Chapter 6: Tuning Neuronal Potassium Channels to the Auditory Environment -- 6.1 Introduction -- 6.2 What Is So Special About Kv3 Potassium Channels? -- 6.3 Brainstem Circuits Underlying Localization of Sounds Have High Levels of Kv3.1 and Kv3.3 Channels -- 6.3.1 Bushy Cells of the Anteroventral Cochlear Nucleus -- 6.3.2 Principal Neurons of the MNTB -- 6.3.3 Other Auditory Brainstem Nuclei -- 6.4 Too Much Kv3.1 Current Produces Errors in Timing -- 6.5 The Properties of Brainstem Neurons Are Plastic -- 6.5.1 Casein Kinase 2 Adjusts the Voltage Dependence of Kv3.1 Current in MNTB Neurons -- 6.5.2 Phosphorylation of Kv3.1 Channels Is Developmentally Regulated -- 6.5.3 Phosphorylation of Kv3.3 Channel Subunits -- 6.6 Long-Term Modulation of Kv3.1 Currents in MNTB Neurons -- 6.6.1 Activity Regulates the Tonotopic Gradient of Kv3.1 Channels -- 6.6.2 Rapid Synthesis of Kv3.1 Channels in Response to Auditory Stimulation Is Regulated by the Fragile X Mental Retardation Protein -- 6.6.3 Regulation of Kv3.1 Channels by Changes in Transcription -- 6.7 Changes in the Tonotopic Gradient of Kv3 Channels Contribute to the Processing of Auditory Information. , 6.8 Unresolved Questions About Channel Modulation in Auditory Neurons -- 6.8.1 Is Channel Modulation Local or Global? -- 6.8.2 Can Accuracy of Transmission Be Altered by Pharmacological Agents? -- 6.9 How Is Modulation of Kv3 Channels Coordinated with Changes in Other Potassium Channels? -- 6.9.1 Kv1 Family Channels -- 6.9.2 Kv2.2 Channels in the Initial Segment -- 6.9.3 Kv11 Channels -- 6.9.4 Sodium-Activated Potassium Channels -- 6.10 Do Changes in Excitability of Brainstem Neurons Contribute to Auditory Learning? -- 6.11 Summary -- References -- Chapter 7: Ontogeny of Human Auditory System Function -- 7.1 Introduction -- 7.2 Development of Conductive Elements -- 7.2.1 External Ear -- 7.2.2 Middle Ear -- 7.2.3 Influences on Auditory Function -- 7.2.3.1 Absolute Sensitivity -- 7.2.3.2 Spatial Hearing -- 7.3 Differentiation of the Human Inner Ear -- 7.3.1 Morphology -- 7.3.2 Physiology -- 7.3.2.1 Otoacoustic Emissions -- 7.3.2.2 Evoked Neural Responses -- 7.3.2.3 Behavioral Responses -- 7.3.3 Development of the Place Principle -- 7.4 Development of Neural Response Properties -- 7.4.1 Frequency Resolution -- 7.4.2 Intensity Representation -- 7.4.2.1 Absolute Sensitivity -- 7.4.2.2 Intensity Discrimination -- 7.4.2.3 Loudness -- 7.4.3 Timbre and Spectral Shape Discrimination -- 7.4.4 Temporal Processing -- 7.4.4.1 Temporal Resolution -- 7.4.4.2 Pitch -- 7.4.4.3 Binaural Hearing -- 7.4.5 Auditory Scene Analysis -- 7.5 Afferent Influences on Auditory System Ontogeny -- 7.5.1 Effects of Exposure to Speech -- 7.5.2 Congenital Hearing Loss Treated with Cochlear Implants -- 7.6 Summary -- References -- Chapter 8: Early Experience and Auditory Development in Songbirds -- 8.1 Introduction -- 8.2 Song Behavior -- 8.3 Basic Hearing -- 8.4 Early Song Experience and Behavior -- 8.4.1 Song Production -- 8.4.2 Song Perception. , 8.5 Early Experience and Auditory Coding -- 8.5.1 Auditory Midbrain -- 8.5.1.1 Auditory Midbrain Function -- 8.5.1.2 Early Experience and Auditory Midbrain Function -- 8.5.2 Auditory Cortex -- 8.5.2.1 Auditory Cortex Organization -- 8.5.2.2 Primary Auditory Cortex -- 8.5.2.3 Early Experience and Primary Auditory Cortex Function -- 8.5.2.4 Secondary Cortex -- 8.5.2.5 Early Experience and Secondary Cortex Function -- 8.6 Summary -- References.

Note: Intro -- The Acoustical Society of America -- Series Preface -- Preface 1992 -- Volume Preface -- Contents -- Contributors -- Chapter 1: Sensory Regeneration in the Inner Ear: History, Strategies, and Prospects -- 1.1 Introduction -- 1.2 Historical Overview of Otic Regeneration -- 1.2.1 Postnatal Generation of Sensory Receptors in Vertebrates -- 1.2.2 Postnatal Addition of Hair Cells in Cold-Blooded Vertebrates -- 1.2.3 Sensory Regeneration in the Avian Inner Ear -- 1.3 Overview of Contents -- 1.4 Conclusions -- References -- Chapter 2: Nonmammalian Hair Cell Regeneration: Cellular Mechanisms of Morphological and Functional Recovery -- 2.1 Introduction -- 2.2 Nonmammalian Hair Cell Regeneration: An Overview -- 2.3 Supporting Cell Populations and Their Functions During Regeneration -- 2.3.1 Identities and Locations of Hair Cell Progenitors in Fish -- 2.3.2 The Role of Peripheral Supporting Cells in Fish -- 2.3.3 Supporting Cell Diversity in Birds -- 2.4 Approaches to Define New Molecular Regulators Using Nonmammals -- 2.4.1 Transcriptional Profiling -- 2.4.2 Genetic and Molecular Screening -- 2.5 Molecular Regulation of Supporting Cells -- 2.5.1 Transcription Factors Regulate Hair Cell Regeneration in Nonmammals -- 2.5.2 Cell-Cell Signaling Molecules That Regulate Hair Cell Regeneration in Birds and Fish -- 2.5.2.1 Notch Signaling -- 2.5.2.2 Wnt Signaling -- 2.5.2.3 Other Signaling Pathways -- 2.5.3 Epigenetic Mechanisms Controlling Nonmammalian Hair Cell Regeneration -- 2.6 Conclusion -- References -- Chapter 3: Cell Junctions and the Mechanics of Hair Cell Regeneration -- 3.1 Introduction -- 3.2 Shape Change Controls Proliferation of Supporting Cells -- 3.3 Actomyosin Contractility at Apical Junctions Accelerates Wound Closure in the Lesioned Vestibular Epithelium. , 3.4 Maturational Reinforcement of Adherens Junctions Coincides with Age-Related Declines in the Plasticity of Mammalian Supporting Cells -- 3.4.1 The Unique Circumferential F-actin Bands in Mammalian Supporting Cells -- 3.4.2 Potential Mechanical Influence of the Thick F-actin Bands that Develop in Mammalian Supporting Cells -- 3.4.3 Structure and Regulation of the Circumferential F-actin Bands in Supporting Cells -- 3.4.3.1 Sarcomeric Actomyosin Network at Cochlear Apical Junctions -- 3.4.3.2 Regulation of the Circumferential F-actin Bands by Rho GTPases -- 3.5 E-cadherin Accumulates at Supporting Cell Junctions in the Mammalian Vestibular Epithelium -- 3.5.1 Hypothesized Role for N-cadherin in Limiting Supporting Cell Proliferation -- 3.5.2 A Special Case: Apical Junctions in the Anolis Lizard -- 3.6 Regulation and Perturbation of Apical Junctions in Mammalian Supporting Cells -- 3.6.1 Potential Interaction of Notch Signaling and E-cadherin Adhesion -- 3.7 Intracellular Signaling Downstream of Mechanical Signals -- 3.7.1 YAP/TAZ and the Hippo Pathway -- 3.7.1.1 YAP-TEAD Regulate Cell Cycle Arrest and Size Control in Hair Cell Epithelia -- 3.7.1.2 YAP-TEAD Signaling in Repair and Regeneration -- 3.7.2 Canonical Wnt Signaling -- 3.8 Supporting Cell-Extracellular Matrix Interactions -- 3.9 Summary -- 3.9.1 A Hypothetical Model for Mechanical Control of Hair Cell Replacement -- 3.9.2 Outstanding Questions and Opportunities -- 3.10 Conclusions -- References -- Chapter 4: Mammalian Hair Cell Regeneration -- 4.1 Introduction -- 4.2 Structural and Developmental Considerations -- 4.2.1 Structure of the Mammalian Vestibular Sensory Epithelia -- 4.2.2 Development of the Vestibular Sensory Epithelia -- 4.2.3 Structure of the Mammalian Auditory Epithelium, the Organ of Corti -- 4.2.3.1 Hair Cell Types -- 4.2.3.2 Supporting Cells. , 4.2.3.3 Features of Organ of Corti Development -- 4.3 Hair Cell Generation and Regeneration in the Immature Inner Ear -- 4.3.1 Generation of Supernumerary Hair Cells -- 4.3.2 Hair Cell Regeneration in the Immature Inner Ear -- 4.3.3 Stem Cells in the Sensory Epithelia -- 4.4 Hair Cell Generation and Regeneration in the Mature Vestibular Sensory Epithelia -- 4.4.1 Characteristics of Spontaneous Regeneration in Adult Mammalian Utricles -- 4.4.2 Origin of Regenerated Hair Cells -- 4.4.3 Functionality of Regenerated Vestibular Hair Cells -- 4.5 Enhancing Hair Cell Regeneration by Phenotypic Conversion in Mature Animals -- 4.5.1 Vestibular Sensory Epithelia -- 4.5.1.1 Notch Pathway Inhibition -- 4.5.1.2 Overexpression of Atoh1 -- 4.5.2 Inducing Hair Cell Regeneration in the Mature Organ of Corti in Vivo -- 4.5.2.1 Overexpression of Atoh1 -- 4.5.2.2 Notch Pathway Inhibition -- 4.5.3 Additional Factors to Promote Differentiation of Regenerated Hair Cells -- 4.5.4 Clinical Trials -- 4.6 Regeneration of Vestibular Hair Cells: Summary -- 4.7 Cochlear Cellular Pathology and Challenges to Hair Cell Regeneration and Recovery of Auditory Function -- References -- Chapter 5: Specification and Plasticity of Mammalian Cochlear Hair Cell Progenitors -- 5.1 Introduction -- 5.2 Induction of the Inner Ear and the Development of Prosensory Patches -- 5.3 Regulation and Function of the Atoh1 Transcription Factor During HC Development -- 5.4 Promotion of Supporting Cell Fate Through Notch-Mediated Lateral Inhibition from Hair Cells -- 5.5 Regulation of Supporting Cell Fate Decisions: Extracellular Signals and Intracellular Transcription Factors -- 5.6 Toward Hair Cell Regeneration: Lessons from Non-mammalian Models and Neonatal Mice -- 5.7 Enhancing Mammalian Hair Cell Regeneration: Reprogramming of Supporting Cells into Hair Cells. , 5.8 Epigenetic Regulation of Gene Expression in the Cochlea -- 5.9 Summary -- References -- Chapter 6: Inner Ear Cells from Stem Cells: A Path Towards Inner Ear Cell Regeneration -- 6.1 Introduction -- 6.1.1 Pluripotent Stem Cells -- 6.2 Two-Dimensional Culture Systems -- 6.2.1 Inner Ear Replacement Parts and Hair Cells from Scratch -- 6.2.2 Hair Cell-Like Cells from Pluripotent Stem Cells -- 6.2.3 Limitations of Two-Dimensional Culture Systems -- 6.3 Three-Dimensional Culture and Organoids -- 6.3.1 Derivation of Inner Ear Organoids -- 6.3.2 Limitations of Three-Dimensional Culture Systems -- 6.4 Stem Cells in the Adult Inner Ear -- 6.4.1 Stem Cells Are the Source of the Strong Regenerative Capacity of the Avian Inner Ear -- 6.4.2 Stem Cells in the Inner Ear of Adult Rodents Are Restricted to the Vestibular System -- 6.5 Stem Cells in the Neonatal Rodent Cochlea -- 6.5.1 Supporting Cells of the Neonatal Organ of Corti Display Stem Cell-Like Capacity -- 6.5.2 Proliferation of Dissociated Neonatal Organ of Corti Supporting Cells Can be Manipulated with Growth Factors and Small Molecules -- 6.6 Emerging New Methods Towards Hair Cell Regeneration -- 6.6.1 CRISPR Genome Editing to Enhance Stem Cell Applications? -- 6.6.2 Supporting Cell Reprogramming -- 6.7 Conclusion -- References -- Chapter 7: Spiral Ganglion Neuron Regeneration in the Cochlea: Regeneration of Synapses, Axons, and Cells -- 7.1 Introduction to Spiral Ganglion Neurons -- 7.1.1 Peripheral Connections of Spiral Ganglion Neurons -- 7.1.2 Glia and Myelination -- 7.1.3 Central Connections of SGNs -- 7.1.4 Neurotrophic Factors -- 7.2 Synaptopathy and Synapse Regeneration -- 7.2.1 Primary Degeneration -- 7.2.2 Secondary SGN Degeneration After Hair Cell Loss -- 7.3 Regeneration of SGN Axons and Guidance of Their Growth -- 7.3.1 Stimulation of Growth by Neurotrophic Factors. , 7.3.2 Intracellular Signaling for Neurite Growth/Retraction -- 7.3.3 Directional Guidance by Neurotrophic Factors -- 7.3.4 Directional Guidance by Substrate Pattern/Materials -- 7.4 Cochlear Implants Present a Model for SGN Regeneration -- 7.4.1 Cochlear Implants Depend on SGN Health -- 7.4.2 Cochlear Trauma and Inflammation Likely Reduce SGN Health and CI Performance -- 7.5 Regeneration of SGNs from Stem Cells -- 7.5.1 Assessments of Success -- References -- Chapter 8: Genetic and Epigenetic Strategies for Promoting Hair Cell Regeneration in the Mature Mammalian Inner Ear -- 8.1 Introduction -- 8.2 Mouse Models for Altering Gene Expression -- 8.2.1 Cre/lox Technology -- 8.2.1.1 Cell Type-Specific and Temporal Control of Recombination -- 8.2.1.2 Generation of Cre and CreERT Mouse Lines -- 8.2.1.3 Characterizing Cre/CreERT Expression -- 8.2.1.4 Interpreting Cre/CreERT Reporter Expression -- 8.2.1.5 Cre/CreERT Efficiency -- 8.2.1.6 Caveats for Cre/CreERT Studies -- 8.2.2 CreERT Alleles Expressed in Supporting Cells -- 8.2.2.1 CreERT Alleles for Adult Auditory Supporting Cells -- 8.2.2.2 CreERT Alleles for Adult Vestibular Supporting Cells -- 8.2.3 Tetracycline-Responsive Gene Regulation -- 8.2.4 CRISPR/Cas Approaches -- 8.2.4.1 Generation of Knockout Mice -- 8.2.4.2 Advantages Over Conventional Mouse Mutagenesis -- 8.2.4.3 Genetic Knock-In Using CRISPR/Cas -- 8.2.4.4 Cas9-Expressing Mouse Lines -- 8.2.4.5 Reducing Off-Target Effects -- 8.2.4.6 DNA Base Editing with Dead Cas9 -- 8.3 Targeting Epigenetic Processes for Hair Cell Regeneration -- 8.4 Virus-Mediated Gene Transfer in Adult Supporting Cells -- 8.4.1 Introduction to Adeno-Associated Virus -- 8.4.1.1 AAV Infection and Tropism -- 8.4.1.2 Recombinant Adeno-Associated Viral Vectors -- Capsid Discovery to Achieve Novel Transduction -- 8.4.1.3 Packaging Capacity. , 8.4.2 Gain of Function in Supporting Cells.