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Cholinergic and noradrenergic modulation of memory and mood.

The current therapies of Alzheimer's disease (AD) are insufficient and novel treatments are necessary. Cholinergic and noradrenergic neurotransmitter systems are involved in memory and mood modulation. An add-on effect of increased noradrenergic signalling in addition to the standard therapy of increased cholinergic signalling has been proposed for AD patients. However, the interaction between the two systems is not well understood. In this proposal, we will evaluate the effects of activating via DREADDs 1) cholinergic neurons in medial septum, which project to hippocampus, 2) noradrenergic neurons in locus coeruleus, which project to medial septum and hippocampus, and 3) cholinergic and noradrenergic neurons. We will evaluate the effect of these different modulations on behaviour (memory and mood) and different brain network properties in a promising AD rat model and in healthy rats. We will look at functional connectivity in the brain, oscillations in local field potentials in hippocampus (which reflect local hippocampal network properties), and whole-brain activity state related to sharp-wave ripples, a neuronal event that occurs within hippocampus and that is associated with memory. Finally, we will assess whether early deficits in functional connectivity and cerebral blood flow can predict long-term behavioural outcome in (untreated) AD rats and whether deficits in these parameters can predict the responsiveness to the treatment (one of the three possible modulations).
Date:1 Oct 2018  →  Today
Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing