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Title: Neurophysiology of the subthalamic nucleus
Author: Atherton, J. F.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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Possibly as many as half the neurones in the STN have an axon collateral with branches off from the main axon and reinnervates the nucleus. This suggests that rather than working autonomously as was previously thought, the neurones of the STN can operate together as a network. Computer models of the STN showed that the level of interconnectivity within the STN would be huge, even if each axon collateral only contacted a small number of the total neurones with dendritic fields that overlapped with it. A network model showed that such a system was capable of switch-like behaviour. At low levels of activity the neurones would act autonomously. However, excitatory inputs could increase the degree of non-synchronous correlation between the activity of neurones in the STN leading them all to enter a high activity state. A single cell model was then developed in order to look at how this high activity state could be terminated. An interesting problem arose in the construction of this model; no known kinetics for the voltage-gated sodium and potassium channels could replicate the high frequency (500Hz) firing rates that are obtained by STN neurones. Intracellular recordings were made in vitro to investigate the mechanisms underlying high-frequency firing in the STN. Using a two-pulse protocol the speed of recovery from inactivation was measured giving an estimate of the inactivation characteristics of the ion channels in these neurones. These experiments showed that the neurones have very slow inactivation kinetics suggesting that STN neurones may have a much shortened refractory period, enabling high frequency firing. Such a mode of operation requires a large, fast potassium current. A potential candidate for this current is the Kv3.l potassium channel, which is strongly expressed by STN neurones.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available