Postnatal Development of Neural Networks in the Healthy and Premature Brain

Abstract

Late fetal and early neonatal life is a period of rapid neurological development, with dramatic structural and functional changes unfolding to create the complex neuronal networks of the mature brain. Disruptions to early life experience can have profound effects on the developing brain, with alterations to network formation that can have life-long impacts. A common adverse early life condition in humans is premature birth, which often results in neurodevelopmental deficits. This project develops a mouse model of prematurity to investigate the impact that being born early has on the development of the sensorimotor networks. It finds, using measures of behavioural development, and cellular and synaptic maturation of neurons that the developing brain is remarkably robust. If an animal can survive the initial dramatic changes of being born, the sensory networks of the brain continue to develop along their typical trajectory. This project further explores the impact of premature birth on sensory network development, with a neuroimaging experiment in human preterm infants. A somatosensory stimulation based functional magnetic resonance imaging paradigm is established to investigate evoked responses in the preterm infant brain. In vivo neuroimaging techniques offer valuable information about the functional development of neuronal networks. This project also utilises a newly established pan- cortical calcium imaging technique to investigate the postnatal development of cortical activity in mice. Recordings of both endogenously generated and sensory stimulated activity in healthy and sensory deprived conditions are made at high spatial and temporal resolution. It finds complex patterns of spontaneous activity across the cortex that have intracortical coordination, that are independent of sensory experience in the first postnatal week. Somatosensation is active from the first postnatal day and the developmental trajectory of evoked cortical activity is mediated by early life sensory experience. This thesis details an investigation into the development of the sensorimotor networks in both healthy and adverse early life environments, discovering both the vulnerability and robustness of their functional development.

Date of Award	19 Mar 2019
Original language	English
Awarding Institution	University of Bristol
Sponsors	Medical Research Council
Supervisor	Michael C Ashby (Supervisor) & Karen Luyt (Supervisor)