C02 Effect of locus ceruleus modulation on behaviour and related target structures in its cortical and hippocampal projection areas: implications for Alzheimer`s disease
The locus ceruleus (LC) represents the chief source of central noradrenaline (NA) in the mammalian brain. Physiologically, NA influences synaptic plasticity and neuronal network function and ultimately behaviour including learning and memory in cortical and hippocampal projection areas. Degeneration of the LC is already present during early Alzheimer`s disease. The central hypothesis of this project is that NA deficiency due to LC degeneration plays a critical role for early memory deficits in AD. We will examine whether LC loss and the effects of amyloid ? (A?) deposition interact to cause aberrant neuronal network activity using molecular and neurochemical analyses combined with multiphoton in-vivo Ca2+ imaging and optogenetic modulation of LC neurons. The project will also explore strategies to reconstitute noradrenergic function in Alzheimer's disease models.