Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.779423
Title: Multiscale modelling of neuronal dynamics and their dysfunction in the developing brain
Author: Rosch, Richard Ewald
ISNI:       0000 0004 7965 1198
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Abstract:
Over the last few decades, an increasing number of neurodevelopmental disorders has been associated with molecular causes - such as genetic mutations, or autoantibodies affecting synaptic transmission. Yet understanding the pathophysiology that leads from particular molecular disruptions at the synapse to patients' signs and symptoms remains challenging, even today. The work presented in this thesis illustrates how computational models can help bridge the explanatory gap between disruptions at the molecular scale and brain dysfunction at the level of integrated circuits. I utilise computational models at different scales of neuronal function, ranging from the neuronal membrane, to integrated cortical microcircuits and whole-brain sensory processing networks. These computational models are informed with, and further constrained by both empirical data derived from a number of model systems of neurodevelopmental disorders, and clinical patient data. The worked examples in this thesis include the biophysical characterisation of an epilepsy-causing mutation in the voltage-gated sodium channel gene SCN1A, calcium imaging in a larval zebrafish model of epileptic seizures in the immature brain, electrophysiological recordings from patients with NMDA receptor antibody encephalitis as well as from a mouse model of the disorder, and pharmacologically induced NMDA receptor blockade in young adults that captures features of acute psychosis and schizophrenia. The combination of this diverse range of empirical data and different computational models offers a mechanistic, multi-scale account of how specific phenotypic features in neurodevelopmental disorders emerge. This provides novel insights both in regard to the specific conditions included here, but also concerning the link between molecular determinants and their neurodevelopmental phenotypes more broadly.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.779423  DOI: Not available
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