New Aspects of Axonal Structure and Function (eBook)

Foreword 5
Development 5
Axonal Function 6
Axons in Circuits 7
Degeneration and Regeneration of Axons 8
Preface 10
Contents 11
Contributors 13
Part I Axons in Development 16
1 Molecular Aspects of Commissural Axon Guidance 17
1.1 Basic Principles of Axonal Navigation 17
1.2 Commissural Neurons as a Model System to Study Axonal Pathfinding 18
1.2.1 Commissural Axon Guidance in the Vertebrate Spinal Cord 18
1.2.1.1 Guidance Toward the Floorplate 19
1.2.1.2 Guidance Across the Floorplate 20
1.2.1.3 Rostral Turning and Longitudinal Projection After Crossing 23
1.2.2 Commissural Axon Guidance in Drosophila melanogaster 25
1.2.2.1 Guidance Toward the Midline 25
1.2.2.2 Guidance Across the Midline 26
1.2.2.3 Longitudinal Projection After Crossing 27
1.3 Open Questions 28
References 28
2 Subplate and the Formation of the Earliest Cerebral Cortical Circuits 33
2.1 Clinical Importance of the Understanding of Early Cortical Circuits 36
2.2 Recent Microarray Screen of Murine Subplate Neurons 38
2.3 Recent Studies of Subplate Neuron Integration into the Cortical and Extracortical Circuitry in Reporter Gene Expressing Mouse Models 38
2.4 Manipulation of the Sensory Periphery Alters Subplate Integration into the Barrel Field 39
2.5 Subplate Cell Populations in Mutants with Cortical Migration Defects 40
2.6 Summary 41
References 42
Part II Axonal Function 46
3 Sodium Signals and Their Significance for Axonal Function 47
3.1 Introduction 47
3.2 Sodium Signals and the Measurement of [Na+]i 48
3.2.1 Sodium Signals in Dendrites and Glial Processes 48
3.2.1.1 Action Potential-Induced [Na+]i Changes 48
3.2.1.2 Synaptically Evoked [Na+]i Changes in Dendrites and Glia 49
3.3 Sodium Signals in Axons 52
3.3.1 Pathophysiological Implications of [Na+]i Changes 56
3.3.2 Possible Physiological Roles of [Na+]i Changes 58
3.4 Conclusions and Outlook 60
References 61
4 New Insights in Information Processing in the Axon 66
4.1 Introduction 66
4.2 Complexity of Axonal Arborization: Branch Points and Varicosities 67
4.3 Functional Computation in the Axon 67
4.3.1 Shaping Action Potential 67
4.3.1.1 Activity-Dependent Broadening of Presynaptic Action Potential 68
4.3.1.2 Activity-Dependent Reduction of Presynaptic Action Potential 69
4.3.2 Signal Amplification Along the Axon 70
4.3.3 Axonal Integration 70
4.4 Propagation Failures 73
4.4.1 Geometrical Factors: Branch Points and Swellings 73
4.4.2 Frequency-Dependent Propagation Failures 75
4.4.3 Frequency-Independent Propagation Failures 79
4.5 Ping-Pong Propagation: Reflection of Action Potential Propagation 80
4.6 Spike Timing in the Axon 82
4.6.1 Axonal Delay Imposed by Axonal Length 82
4.6.2 Extra Delays Imposed by Axonal Irregularities and Ion Channels 84
4.6.3 Ephaptic Interactions and Axonal Spike Synchronization 85
4.6.4 Electric Coupling in Axons and Fast Synchronization 85
4.7 Conclusion 86
4.7.1 Increased Computational Capabilities 86
4.7.2 Future Directions and Missing Pieces 86
References 88
5 Electrical Coupling of Axons 95
5.1 Mechanisms of Electrical Coupling 95
5.2 Methodological Issues 98
5.3 Axo-axonal Synapses 100
5.4 Physiological Significance of Axo-axonic Gap Junctions 105
References 107
6 To Myelinate or Not to Myelinate? 113
6.1 Introduction 113
6.2 Results 115
6.2.1 Axonal Cost with Fixed Conduction Delay 115
6.2.2 Axon with a Finite Conduction Delay Cost 117
6.2.3 Comparison with Experiments 119
6.3 Discussion 121
6.4 Conclusions 121
6.5 Methods 122
References 123
Part III Axons and Neuronal Circuits 124
7 An Axonal Perspective on Cortical Circuits 125
7.1 Introduction 125
7.2 Local Circuits 127
7.3 Capturing Axon Morphology 128
7.4 The Problem of Choice 135
7.5 Wiring Neurons 137
7.6 Improving Peters Rule 139
7.7 Computation in Daisy Architectures 141
References 144
8 Axons Predict Neuronal Connectivity Within and Between Cortical Columns and Serve as Primary Classifiers of Interneurons in a Cortical Column 148
8.1 Definition of a Cortical Column by the Geometry of Axonal Domains 150
8.2 Inference of Synaptic Connectivity Within a Cortical Column 151
8.3 Classification of Inhibitory Interneurons Based on Their Innervation Domains with Reference to Cortical Columns 153
8.4 Local Versus Lateral Inhibitors in Neocortex 155
8.5 Subsequent Classification Steps 158
8.6 Summary 159
References 159
9 The Axon of Excitatory Neurons in the Neocortex: Projection Patterns and Target Specificity 163
9.1 Introduction 163
9.2 Highly Variable Axonal Domains of Neocortical Excitatory Neurons 164
9.3 Layer 2/3 165
9.4 Layer 4 167
9.4.1 Spiny Stellate and Star Pyramidal Neurons 167
9.4.2 Star Pyramidal Cells 169
9.5 Layer 5 171
9.5.1 Sublamina 5A 171
9.5.2 Sublamina 5B 172
9.6 Layer 6 174
9.6.1 Sublamina 6A 174
9.6.2 Sublamina 6B 176
9.7 Subcellular Axonal Targets 177
9.8 Outlook 178
References 179
Part IV Axons and Degeneration/Regeneration 185
10 Axon Degeneration: Mechanisms and Consequences 186
10.1 Introduction 186
10.2 The Axon as a Functionally Distinct Compartment 186
10.3 Axon Degeneration 189
10.3.1 Morphological Changes 189
10.3.2 Protein Expression Changes 191
10.3.3 Wlds 192
10.3.4 Pathways Involved in Axonal Degeneration 195
10.3.4.1 Mitogen-Activated Protein Kinases (MAPKs) 196
10.3.4.2 Mitochondria 197
10.3.4.3 Calcium/Calpains 197
10.3.4.4 Ubiquitin Proteasome System 198
10.4 Lessons from Anuclear Models of Degeneration 200
10.5 Cellular Responses in Axon Degeneration 201
10.5.1 Ensheathing Cells 201
10.5.2 Macrophages 202
10.6 Concluding Remarks 204
References 205
11 Regeneration After CNS Lesion: Help from the ImmuneSystem? 213
11.1 Introduction 213
11.2 Wound Healing Responses of the CNS 214
11.2.1 Inflammation in Autoimmune Neurodegeneration Versus CNS Repair After Trauma 214
11.2.2 Multi-phase Responses of the CNS After Trauma 215
11.3 The Adaptive Immune System in CNS Injury 220
11.3.1 T Cells in the Healthy and Injured CNS 220
11.3.2 Self-Reactive T Cells in CNS Injury 221
11.3.3 Neuronal Injury in T Cell-Deficient Mice 222
11.3.4 The Controversy About ''Protective Autoimmunity'' 222
11.4 T-Helper Cell Subpopulations in CNS Injury and Repair? 223
11.4.1 Analysis of the Th1/Th2 Ratio 224
11.4.2 Are Subpopulations of T Cells Responsible for Neuroprotective and Pro-regenerative Effects? 225
11.5 CNS Injury-Induced Immunosuppression Results in a Systemic Th2 Shift 226
11.6 Are Beneficial T-Cell Effects Exclusively Attributable to Th2 Cells? 226
11.7 How May T Cells Contribute to CNS Repair? 227
11.7.1 Neurotrophin Secretion by T Cells 228
11.7.2 Modulation of Microglia Functions 228
11.7.3 Modulation of Endogenous and Exogenous Stem Cells 228
11.7.4 Anti-inflammatory T-Cell Effects 228
11.7.5 Direct Stimulation of Axon Growth by T-Cell Cytokines 229
11.8 Future Perspectives 229
References 229
Index 237