This book aims to provide a comprehensive and timely review of new findings in motoneuron research. Recent findings have revealed that motoneurons are more complex and have more extensive functions than previously imagined. Some of the molecular and genetic pathways that orchestrate the development of motoneurons have been discovered, as have the mechanisms responsible for the selective innervation of muscles by specific pools of motoneurons. These novel findings are revolutionizing ideas about the function of motoneurons and have important implications for motoneuron disease.
Chapters from several of the foremost figures in the field are included in this book and will emphasize how basic science is the engine driving the discovery of novel treatments for degenerative motoneuron diseases. Cutting edge developments in the use of pluripotent stem cells to correct motoneuron disease will be also be covered. This book would be useful to students of basic motoneuron physiology, locomotor behavior and motor control. This book would also be of interest to professional neuroscientists, neurologists, and neurosurgeons.
Author(s): Michael J. O'Donovan, Mélanie Falgairolle
Series: Advances in Neurobiology, 28
Publisher: Springer
Year: 2022
Language: English
Pages: 402
City: Cham
Preface
Contents
Part I: Motoneuron Development
Establishing the Molecular and Functional Diversity of Spinal Motoneurons
1 Introduction
2 Anatomical and Functional Diversity of Spinal Motoneurons
3 Specification of Spinal Motoneuron Class Identity
4 Early Patterning of Spinal Motoneurons Along the Rostrocaudal Axis
5 Developmental Mechanisms of Motoneuron Diversification
Hox Genes and the Specification of LMC Neurons and Divisional Subtypes
Intrinsic Programs of Motoneuron Pool Specification
Target-Dependent Regulation of Motoneuron Pool Identities
Development of Phrenic Motor Column (PMC) Neurons
Development and Diversity of Preganglionic Column (PGC) Neurons
Specification Hypaxial (HMC) and Medial Motor Column (MMC) Neurons
Establishing Motoneuron Functional Subtype Diversity
6 Evolution of Spinal Motoneuron Organization and Function
Origins of Tetrapod Limb Motoneurons
Hox Genes and the Evolution of Motoneuron Segmental Organization and Diversity
Divergence of Axial Motoneuron Specification Programs in Fish
7 Assembly of Proprioceptive Sensory-Motor Circuits
Specification of Proprioceptor Sensory Neuron Class Identities
Target-Derived Signals Regulate pSN Subtype Identity and Connectivity with Motoneurons
Roles of Motoneuron Subtype Identity in Sensory-Motor Circuit Assembly
Evidence for Coordinate Regulation of pSN-Motoneuron Connectivity by Hox Genes
8 Motoneurons as Regulators of Circuit Assembly and Function
9 Conclusions
References
Chloride Homeostasis in Developing Motoneurons
1 Introduction
2 NKCC1 and KCC2 Molecular Properties
3 Chloride Homeostasis in Developing Motoneurons
Anatomical Maturation of CCCs
Modulation of the Chloride Homeostasis in Developing Motoneurons
Functional Consequences
4 Pathological Considerations
5 Concluding Remarks
References
Normal Development and Pathology of Motoneurons: Anatomy, Electrophysiological Properties, Firing Patterns and Circuit Connectivity
1 Introduction and Historical Retrospective
2 Classification of Motoneurons
3 The Development of the Electrophysiological Properties and Firing Patterns of Motoneurons
4 Development of Motoneuron Spinal Cord Circuitry
5 Motoneuron Function Is Altered in Disease States
References
Homeostatic Regulation of Motoneuron Properties in Development
1 Introduction
2 Chick Embryo Homeostatic Plasticity
Synaptic Scaling
Homeostatic Intrinsic Plasticity
3 Translation of Findings in Chick Embryo to Other Systems
Nicotine Exposure to Developing Rat Hypoglossal Motoneurons
Scaling Induced in Zebrafish Motoneurons Did Not Alter Motor Activity
Altered Levels of Neurotransmission Can Trigger HIP in Fly Motoneurons
4 Novel Homeostatic Principles in Motoneurons from Studies in the Developing Fly and Frog
Identification of Signaling Pathways in Fly Embryo Motoneurons
Presynaptic Homeostatic Plasticity at the Fly Neuromuscular Junction
Channel Coregulation Mediates HIP
Homeostatic Regulation of Neurotransmitter Specification in Embryonic Xenopus Motoneurons
5 Summary
References
Part II: Motoneuron Connectivity and Function
Homeostatic Plasticity of the Mammalian Neuromuscular Junction
1 The NMJ Allows for Detailed Measurement of Parameters Governing Synaptic Function
2 Homeostatic Synaptic Plasticity at the Mouse NMJ
3 Homeostatic Plasticity of Synaptic Function Triggered by Block of Action Potentials
Regulation of Quantal Amplitude
Regulation of Probability of Release (p)
Summary of Changes in Synaptic Function Following Block of Action Potentials
4 Homeostatic Plasticity of Synaptic Function Triggered by Partial Block of AChRs
Regulation of the Number of Releasable Vesicles (n)
Homeostatic Plasticity of Motoneuron Excitability Following Partial Block of AChRs
Summary of Homeostatic Changes in Synaptic Function and Their Implications for Disease
5 Technical Considerations
Preventing Muscle Contraction and Activation of Muscle Na Channels
Pros and Cons of Recording Configurations
References
Diversity of Mammalian Motoneurons and Motor Units
1 Introduction
2 Alpha, Beta and Gamma Motoneurons
3 Classification of Muscles Fibers and Motor Units
4 Contractile Properties of Motor Unit Types
5 Motoneuron Electrophysiological Properties Depend on Their Motor Unit Type
6 Anatomical and Synaptic Properties of the Neuromuscular Junctions Depend on Their Motor Unit Type
7 Conclusion
References
Synaptic Projections of Motoneurons Within the Spinal Cord
1 Projections of Motoneurons to Renshaw Cells
Co-transmission to Renshaw Cells
2 Recurrent Excitation Between Motoneurons
3 Other Synaptic Targets of Motoneurons
4 Conclusions
References
Recruitment of Motoneurons
1 Introduction
2 Size Principle
3 Intrinsic Properties
4 Synaptic Properties
5 Neuromodulation
6 Conclusion
References
Electrical Properties of Adult Mammalian Motoneurons
1 Introduction
Foundational Studies of Motoneuron Properties
2 Passive Properties of Motoneurons and Elementary Cable Theory
3 Motoneuron Transition Properties
Sag and Post-inhibitory Rebound
Rheobase
Action Potential Characteristics
Threshold and Rising Phase
Repolarisation Phase and fAHP
Afterdepolarisation
Medium Afterhyperpolarisation
4 Repetitive Firing Properties of Motoneurons
Spike Frequency Adaptation
5 Modulation of Motoneuron Properties
Somatic Output Amplification: C-Bouton Synapses
SK Channels
KV2.1 Channels
Other Proteins Located at C-Bouton Synapses
C-Boutons and Intracellular Calcium Signalling
Dendritic Input Amplification: Persistent Inward Currents
Modulation of PICs: Neurotransmitter Systems
PICs, Repetitive Firing, and Synaptic Amplification
Termination of PICs
PICs and Motor Pools
6 Other Voltage- and Time- Varying Currents
7 Human Motor Unit Recordings
Fatigue in Human Motoneurons
PICs in Human Motoneurons
8 Conclusion
References
The Cellular Basis for the Generation of Firing Patterns in Human Motor Units
1 Introduction
2 Advancing Our Understanding of Human Motor Commands with the Help of Population Motor Unit Recordings
3 Classic Studies on the Recruitment of Motor Units
4 Effects of Differences in the Distribution of Synaptic Input to Low Versus High Threshold Motoneurons on Their Recruitment Patterns
5 Classic Studies on Rate Modulation in Motor Units
6 Fundamental Role of Neuromodulatory Inputs in Shaping Nonlinear Human Motor Unit Firing Patterns
7 Characteristics of Motor Unit Firing Patterns That Provide Estimates of Cellular Mechanisms: Estimation of Motoneuron PICs from Motor Unit Firing Patterns
8 Characteristics of Motor Unit Firing Patterns That Provide Estimates of Cellular Mechanisms: Estimation of the Spike Afterhyperpolarization
9 Characteristics of Motor Unit Firing Patterns That Provide Estimates of Cellular Mechanisms: Estimation of Motoneuron Post-synaptic Potentials from Motor Unit Firing Patterns
10 Computer-Based Simulations to Study the Synaptic Organization of Motor Commands
11 Implementing Supercomputer-Based Simulations to Estimate Excitation, Inhibition and Neuromodulation
12 Conclusion
References
Motoneuronal Regulation of Central Pattern Generator and Network Function
1 Introduction
2 The Role of Motoneurons in Initiating Spontaneous Bursting in the Developing Spinal Cord
3 Excitatory Effects of Ventral Root Stimulation on Neonatal Mammalian Spinal Networks
4 Motoneuronal Regulation of Locomotion
5 Ventral Root Afferents
6 Optogenetic Manipulation of Motoneuron Activity During Locomotion
7 Motoneuronal Regulation of Central Pattern Generating Circuitry in Non-mammalian Vertebrates
8 Concluding Remarks
References
Extraocular Motoneurons and Neurotrophism
1 Introduction
2 Discharge Characteristics of Extraocular Motoneurons
3 Quantitative Analysis of Extraocular Motoneuron Firing Rate
4 Firing Pattern of Abducens Motoneurons
Discharge of Abducens Motoneurons During Fixations
Discharge of Abducens Motoneurons During Saccades
Discharge of Abducens Motoneurons During Vestibularly-Induced Eye Movements
5 MIF and SIF Extraocular Motoneurons: Is There a Functional Segregation?
Singly and Multiply Innervated Muscle Fibers
Anatomical Evidence
Physiological Evidence
6 Response of Extraocular Motoneurons to Injury and Administration of Neurotrophic Factors
Axotomy of Extraocular Motoneurons and Administration of Neurotrophic Factors During Postnatal Development
Effects of Axotomy on the Discharge and Synaptic Properties of Extraocular Motoneurons in Adult Mammals
BDNF and NT-3: Two Neurotrophins with Complementary Actions on the Function/Structure of Extraocular Motoneurons
NGF Activity in Extraocular Motoneurons
VEGF: A Powerful Neurotrophic Factor for Extraocular Motoneurons
7 Higher Resistance of Extraocular Motoneurons to Degeneration in ALS
8 Conclusions and Perspectives
References
Part III: Motoneuron Disease
Motoneuron Diseases
1 Introduction
2 What Some Numbers Tell About MNDs
3 The Different Facets of Genetics in MNDs
Sporadic Does Not Equate Non-genetic in MNDs
Same Phenotype Due to Mutations in Different Genes
Different Phenotypes Due to Mutations in the Same Gene
4 The Devil Is in the Details
5 Onset and Neuromuscular Junction Remodeling in MNDs
Mechanisms of Axon Pathology in MNDs
6 Non-cell Autonomous Drivers of Neurodegeneration in MNDs
Glial Cells as Motoneuron Death Drivers in MNDs
Other Immune Cells as Modulators of Neurodegeneration in MNDs
References
Electrical and Morphological Properties of Developing Motoneurons in Postnatal Mice and Early Abnormalities in SOD1 Transgenic Mice
1 Introduction
2 Altered Sensorimotor Development in SOD1 Mice
3 Electrical Properties of Developing Motoneurons in Postnatal Mice
Early Changes in Electrical Properties of Lumbar Motoneurons from WT Mice
Early Alterations in Electrical Properties of Lumbar Motoneurons from SOD1 Mice
4 Morphological Properties of Developing Motoneurons in Postnatal Mice
Early Changes in Morphological Properties of Lumbar Motoneurons in WT Mice
Early Changes in Morphological Properties of Lumbar Motoneurons in SOD1 Mice
5 Discussion
Possible Mechanisms Involved in Pathological Alterations of Dendritic Tree
Synaptic Activity and NMDA
Maturation of Motoneurons
6 Conclusion
References
From Physiological Properties to Selective Vulnerability of Motor Units in Amyotrophic Lateral Sclerosis
1 Introduction
2 Selective Vulnerability of Motor Units to ALS
3 Excitability Changes in Motoneurons Is a Determinant of Their Vulnerability in ALS
4 Molecular Pathways Linking Excitation/Excitability to Vulnerability
5 Conclusion
References
Index
