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Action selection in the striatum: Implications for Huntington's disease

Tomkins, Adam R (2015) Action selection in the striatum: Implications for Huntington's disease. PhD thesis, University of Sheffield.

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Although the basal ganglia have been widely studied and implicated in signal processing and action selection, little information is known about the active role that the striatal microcircuit plays in action selection in the basal ganglia-cortical-thalamic loops. To address this knowledge gap we use a large scale three dimensional spiking model of the striatum, combined with a rate coded model of the basal ganglia-cortical-thalamic loop, to asses the computational role the striatum plays in action selection. We identify robust transient phenomena generated by the striatal microcircuit, which temporarily enhances the difference between two competing cortical inputs. We show that this transient is sufficient to modulate decision making in the basal ganglia-thalamo-cortical circuit. We also find that the transient selection originates from a novel adaptation effect in single striatal projection neurons, which is amenable to experimental testing. Finally, we compared transient selection with models implementing classical steady-state selection. We challenged both forms of model to account for recent reports of paradoxically enhanced response selection in Huntington's disease patients. We found that steady-state selection was uniformly impaired under all simulated Huntington's conditions, but transient selection was enhanced given a sufficient Huntington's-like increase in NMDA receptor sensitivity. I propose a mechanistic underpinning to a novel neural compensatory mechanism, responsible for improved cognition in severe neuro-degeneration. Thus, our models provide an intriguing hypothesis for the mechanisms underlying the paradoxical cognitive improvements in manifest Huntington's patients, which is consistent with recent behavioural data.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Engineering (Sheffield) > Computer Science (Sheffield)
The University of Sheffield > Faculty of Science (Sheffield) > Computer Science (Sheffield)
Identification Number/EthosID: uk.bl.ethos.675047
Depositing User: Mr Adam R Tomkins
Date Deposited: 11 Dec 2015 15:26
Last Modified: 03 Oct 2016 12:19
URI: http://etheses.whiterose.ac.uk/id/eprint/10480

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