Neuropharmacological modulation of functional brain imaging signals in awake and anaesthetized rats. (360G-Wellcome-093223_Z_10_Z)

Despite much research, there are still significant gaps in our understanding of what neuroimaging signals tell us about neuronal activity. Firstly, almost all previous research addressed to this question has utilized anaesthetized animals despite established effects of anaesthesia on neuronal, haemodynamic and neurovascular function. Secondly, little work has investigated the neurophysiological basis of neuroimaging signals in important subcortical structures. Thirdly, little is known about how experimental, disease-related, or therapeutic alterations in the function of major neurotransmitter systems such as the serotonin system affects the relationship between neuronal and fMRI responses. This project is centred on an experimental design that will provide data to address each of these gaps in current knowledge. In both awake and anaesthetized rats, we propose to determine the relationships between the neuronal, metabolic and fMRI responses to activation of two subcortical structur es of major clinical and scientific importance: the amygdala and the striatum. We will then determine the effects of alterations in serotonergic neurotransmission upon these relationships. To achieve this, we will combine in-vivo measurements of neuronal activity (electrophysiology), tissue oxygen and glucose (voltametry) and fMRI signals (both BOLD and CBV imaging) with pharmacological and electrical stimulation methods in (trained) awake and anaesthetized rats.