Nervous System Regeneration in the Invertebrates

Invertebrate animals represent a diversity of solutions to life's challenges. Success in a wide range of environments has been achieved by an almost bewildering range of invertebrate body forms. These body forms are reflected in the wonderful diversity of their nervous systems. Despite this apparent diversity, studies of the development of invertebrates and vertebrates are yielding common themes at the molecular level. Likewise, the phenome­ non of neural regeneration is based upon properties intrinsic to neurons and responses to a remarkably conserved chemical lan­ guage. This monograph focuses on the diversity and commonal­ ity of responses to neural injury. The rough and tumble of life may frequently damage some part of the body, particularly the appendages or sensory sys­ tems. The nervous system is usually involved in repair of other body systems and often may itself require repair. Some animals are particularly successful in regenerating the nervous system or body parts. We particularly marvel at these feats of regeneration because we human beings are not particularly successful, despite our relatively long life and the advantages that would seem to accrue from such repair. It is no wonder that we would hope to learn the secrets of the more successful animals and strive to emulate them! Mechanisms of neural regeneration are often more acces­ sible in invertebrates than in vertebrates because questions of specificity are more easily addressed using the identifiable neu­ rons of the relatively simpler nervous systems of some inverte­ brates.

Contenu

1 The Phenomenon of Neural Regeneration.- 1.1 How Shall We Define Neural Regeneration?.- 1.1.1 What Systems Are Involved?.- 1.1.2 Intrinsic and Extrinsic Factors Compromise Repair.- 1.1.3 Neural Injury Reinitiates Growth.- 1.1.4 Injury Tests the Limits of Neural Plasticity.- 1.2 Replacement of Neurons.- 1.2.1 Where Will New Neurons Come From?.- 1.2.2 How Will New Neurons Find Their Way?.- 1.2.3 Which Animals Can Replace Neurons?.- 1.2.4 What Factors Delineate Neurogenesis?.- 1.3 Regrowth of Neurites.- 1.3.1 Incidence of Neurite Repair.- 1.3.2 Comparisons Between Development and Regeneration.- 1.4 A Cost-Benefit Analysis of Neural Regeneration.- 1.5 Rationale for Studying Invertebrate Regeneration.- 1.5.1 Invertebrates Offer the Simplest Systems.- 1.5.2 Invertebrates Offer a Great Diversity of Solutions.- 1.6 Conclusions.- 2 A Survey of Neural Repair in Invertebrates.- 2.1 Introduction.- 2.2 Cnidaria: Neural Structure and Behavior.- 2.2.1 Examples of Regeneration.- 2.2.2 Regeneration in Hydra.- 2.3 Ctenophora: Comb Jellies.- 2.4 Platyhelminthes: The Simplest Bilateral Nervous System.- 2.4.1 Planarians: Masters of Body Regeneration.- 2.4.2 Role of the Nervous System in Body Repair.- 2.4.3 Repair of the Nervous System.- 2.5 Nemertea: Ribbon Worms.- 2.6 Nematoda: Roundworms.- 2.7 Annelida: Introduction to the Phylum.- 2.7.1 Polychaetes.- 2.7.2 Oligochaetes.- 2.7.3 Hirudinea.- 2.8 Arthropoda: Neural Organization and Repair.- 2.8.1 Reinnervation of Muscle.- 2.8.2 Refinement of Connectivity.- 2.8.3 Molting and Regeneration.- 2.8.4 Regeneration of Sensory Cells.- 2.9 Mollusca: Unsegmented Animals with a Range of Cephalization.- 2.9.1 Gastropods, The Snails and Slugs.- 2.9.2 Responses to Naturally Occurring Injuries.- 2.9.3 Axon Regeneration.- 2.9.4 CNS Regeneration.- 2.10 Echinodermata: The Spiny Deuterostomes.- 2.11 Chordata: Our Own Phylum.- 3 Early Responses to Neural Injury.- 3.1 Introduction.- 3.2 Immediate Responses of Injured Neurons.- 3.2.1 Is the Injury Discharge a Cry for Help?.- 3.2.2 Basis of an Injury Discharge.- 3.2.3 Effects of Depolarization and Ca2+ Entry.- 3.2.4 Repairing the Axon Membrane.- 3.2.5 Changes in Excitability Following Axotomy.- 3.2.6 Excitability Changes: Was Injury the First Teacher?.- 3.3 Growth Following Axotomy.- 3.3.1 Initial Outgrowth is Independent of Sorna Responses.- 3.3.2 Retrograde Signals.- 3.3.3 Anatomical Correlates of the Sorna Response.- 3.3.4 Metabolic Adjustments Associated with Regeneration.- 3.3.5 Under What Conditions Is Regeneration Initiated?.- 3.3.6 Speculation on the Role of Diffusible Factors in Regeneration.- 3.4 Survival of Anucleate Axon Segments.- 3.4.1 Mechanisms of Distal Segment Survival.- 3.4.2 Consequences of Distal Segment Survival.- 3.4.2.1 Target Support by Surviving Distal Segments.- 3.4.2.2 Pathway Preservation.- 3.4.2.1 Proximal and Distal Segment Fusion.- 3.4.2.2 Experimental Approaches to Axonal Fusion.- 3.1 Responses of Nonneural Cells to Injury.- 3.2 What Activates Responses in Uninjured Neurons?.- 3.3 Conclusions.- 4 Pathfinding by the Growth Cone.- 4.1 Introduction.- 4.2 Growth Cone Morphology.- 4.3 Growth Cone Extension.- 4.3.1 Membrane Addition.- 4.3.2 Reshaping the Cytoskeleton.- 4.3.3 Responses to the Environment.- 4.4 Ion Channels in the Growth Cone.- 4.4.1 Recording Channel Activity.- 4.4.2 Dynamics of Growth Cone Channel Distribution.- 4.4.3 Substrate Effects on Growth Cone Channels.- 4.4.4 Channel Expression Reflects Growth State.- 4.4.5 Electrical Synapses and Intercellular Communication.- 4.4.6 Developmental Regulation of Channel Expression.- 4.4.7 Sensitivity to Electrical Fields.- 4.4.8 Roles of Electrical Activity in Growing Neurites.- 4.4.9 Roles of Calcium.- 4.4.9.1 Calcium and the Cytoskeleton.- 4.4.9.2 Sprouting and Collapsing.- 4.4.9.3 Ca2+ Effects Mediated by Second Messengers.- 4.5 Responses of Growth Cones to Neurotransmitters.- 4.6 Differentiation Following Growth Cone Interactions.- 4.7 Receptors and Molecular Cues in the Environment.- 4.7.1 Functions of External Signals.- 4.7.2 Binding and Recognition Systems.- 4.7.2.1 Introduction.- 4.7.2.2 Homophilic Binding: Interactions between Like Molecules.- 4.7.2.3 Heterophilic Binding: Interactions between Unlike Molecules.- 4.7.2.4 Identification of Glycoproteins.- 4.7.2.5 Antibodies, Blockers and Mutations Disrupt Pathfinding.- 4.7.2.6 Cues Expressed in Gradients.- 4.8 Conditioned Medium and Growth Promotors.- 4.8.1 Growth Requirements in Culture.- 4.8.1.1 Growth Factors in Gastropod Conditioned Medium.- 4.8.1.2 Neurosecretory Products as Growth Factors.- 4.8.1.3 Insulin-Like Molecules Support Sprouting.- 4.8.1.4 Inhibitors of Sprouting.- 4.8.2 Culture Influences on Branching Pattern.- 4.9 Designing Culture Conditions.- 4.10 Conclusions.- 5 Synapse Formation and Alteration During Regeneration.- 5.1 Introduction.- 5.1.1 Comparing Synaptogenesis in Regeneration and Development.- 5.1.2 Novel Connectivity in Regenerated Nervous Systems.- 5.1.3 Reduced Plasticity in Regenerating Neurons.- 5.1.4 Circuits Reformed in Vivo and in Vitro.- 5.2 The Road to Recovery.- 5.2.1 Behavior of Injured Animals.- 5.2.2 Connectivity Changes and Hypersensitivity.- 5.2.3 Remodeling of Connections.- 5.2.4 Consequences of Deafferentation.- 5.2.4.1 Effects of Sensory Deprivation.- 5.2.4.2 Central Compensation for Sensory Deficits.- 5.2.5 Compensation for Ablated Ganglia.- 5.2.6 Ganglion Regeneration.- 5.3 How Neurons Select Targets.- 5.3.1 Limitation of Choices by Pathway Cues.- 5.3.2 Cell-Adhesion Compatibility in Synaptogenesis.- 5.3.3 Specific Recognition Systems.- 5.3.3.1 Specificity in Arthropod Neuromuscular Innervation.- 5.3.3.2 Specific Connections Made by Transplanted Neurons.- 5.3.3.3 Mutants Elucidate Synaptic Specificity.- 5.4 Development of a Functioning Synapse.- 5.4.1 Neurotransmitters in Synapse Formation.- 5.4.2 Targets May Induce Excitation-Secretion Coupling.- 5.4.3 Alterations in Ca2+ Channel Distribution.- 5.4.4 Electrical Activity in Synapse Formation.- 5.4.5 Responses to Growth Cone Contact with Target.- 5.5 The Role of Competition.- 5.6 Conclusions.- References.