Use this URL to cite or link to this record in EThOS:
Title: All-optical assay to study biological neural networks
Author: Afshar Saber, Wardiya
ISNI:       0000 0004 8502 5513
Awarding Body: University of St Andrews
Current Institution: University of St Andrews
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
As life span increases, neurodegenerative diseases such as dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis become an emerging problem in modern society. In particular Alzheimer's disease (AD), characterized by a progressive cognitive impairment and memory loss, is the dominant cause of disability in people aged over 60. Due to the lack of accurate models, understanding the disease mechanisms and developing a cure for AD remains challenging. However, a novel approach based on human induced pluripotent stem cell (iPSC) technology may offer an opportunity to overcome the limitations of the current models. These cells obtained by reprogramming patient's somatic cells such as fibroblasts can be differentiated in vitro into various types of neural cells which further develop complex networks. To explore these heterogeneous neural networks, it is often critical to understand the activity of multiple neurons and how they communicate with each other. The work presented in this thesis focuses on the development of the first molecular optogenetic tool called OptoCaMP used in an all-optical assay enabling simultaneous stimulation and calcium imaging of a large population of neurons with a single-cell readout. This assay was further adapted to study the spread of excitation in a network thus allowing the quantification of its connectivity. The application of this assay in conditions where the neuronal connectivity was enhanced or decreased successfully demonstrated its sensitivity to changes in connectivity. This assay together with the iPSC technology bring the promise to greatly improve disease models studies and drug screening platforms.
Supervisor: Gunn-Moore, Frank J. Sponsor: Cunningham Trust ; Wellcome Trust ; RS MacDonald Charitable Trust ; Engineering and Physical Sciences Research Council (EPSRC) ; University of St Andrews
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: TA1522.A4 ; Optogenetics ; Alzheimer's disease--Research ; Nervous system--Degeneration--Treatment ; Stem cells--Technological innovations ; Neurons--Physiology