Cholinergic and noradrenergic neuromodulation 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 whole-brain functional connectivity and cerebral blood flow in a promising rat model for Alzheimer's disease. 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).

Keywords:EXPERIMENTAL STUDY

Disciplines:Medical imaging and therapy not elsewhere classified, Behavioural neuroscience, Cognitive neuroscience