Rosch, Richard Ewald;
(2019)
Multiscale Modelling of Neuronal Dynamics and Their Dysfunction in the Developing Brain.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Rosch_thesis.pdf Download (54MB) | Preview |
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.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Multiscale Modelling of Neuronal Dynamics and Their Dysfunction in the Developing Brain |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/ 4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10074472 |
Archive Staff Only
 |
View Item |
