Spike Train Propagation in the Axon of a Visual Interneuron, the Descending Contralateral Movement Detector of Locusta Migratoria

....................................................................................................................... ii ACKNOWLEDGEMENTS ............................................................................................... iv TABLE OF CONTENTS .................................................................................................... v LIST OF FIGURES AND ILLUSTRATIONS................................................................ viii LIST OF ABREVIATIONS ............................................................................................... x CHAPTER 1: INTRODUCTION ....................................................................................... 1 Hypoxia-tolerance .......................................................................................................... 2 The energetic cost of spike trains ................................................................................... 3 Cost/benefit analysis of spike trains in high performance cells ..................................... 7 Spike train propagation in a high performance visual interneuron ................................ 8 Hypoxia-tolerance in the locust ................................................................................... 11 The AMP-activated protein kinase cascade; balancing supply with demand .............. 12 The role of hyperpolarization-activated cyclic nucleotide-gated channelsin neuronal performance under ideal and hypoxic conditions ..................................................... .. 13 Hypothesis.................................................................................................................... 16 CHAPTER 2: MATERIALS AND METHODS .............................................................. 18 Animals and preparations ............................................................................................ 18 Evoked-stimulus and measured response .................................................................... 22 Experimental proceedure ............................................................................................. 24 Data analysis ................................................................................................................ 28 vi CHAPTER 3: RESULTS .................................................................................................. 35 Spike train propagation is compromised in hypoxic nerve cords ................................ 35 Effects of hypoxia on spike train propagation are not strictly uniform along the entire length of DCMD .......................................................................................................... 43 Octopamine attenuates the effects of hypoxia in the ventral nerve cord on spike train propagation .................................................................................................................. 44 Bath applications of metformin or ZD7288 compromise spike train propagation in preparations with normoxic nerve cords ...................................................................... 46 Metformin and ZD7288 affect the amplitude, duration and shape of action potentials as interpereted from their triphasic waveforms recorded extracellularly .................... 52 Non-uniform additive increases in conduction delay over the entire length of DCMD axon are significant in terms of arrival time and may result in the corruption of temporally encoded information .................................................................................. 57 CHAPTER 4: DISCUSSION ............................................................................................ 64 Axonal conduction velocities observed under normoxic conditions are not supported by DCMD during hypoxia ........................................................................................... 67 DCMD axon fails to support the propagation of high frequency action potentials during hypoxia: Consequences for temporal coding ................................................... 73 Reduced DCMD performance during hypoxia: a trade off resulting in maladaptive behaviour or an inherently adaptive strategy? ............................................................. 81 Mechanism of metformin action on DCMD axon ....................................................... 85 Conclusion: The virtues of DCMD as a model system ............................................... 87