The successful treatment of memory impairments and neurodegenerative disorders critically depends on our understanding of the storage and recollection of memory episodes. Specifically, an understanding of the interaction between amnesic and neurodegenerative syndromes would aid the development of effective treatments. One of the key questions in neuroscience is: how do brain networks encode experience-dependent memory? Answering this question will give us a universal tool to treat multiple brain disorders. The anatomical focus of my current research interests is the interaction between limbic, basal forebrain and nigro-striatal circuits as a possible candidate for interregional coordination of spatial navigation and context-dependent components of episodic memory. I plan to examine if 1) neuromodulation from cholinergic neurons in forebrain and pontine tegmentum and 2) neuromodulation from dopaminergic and GABA-ergic neurons from ventral tegmental area (VTA) and substantia nigra can regulate the properties of spatial experience-dependent spatial navigation to guide behaviour. Understanding the fundamental principles of this inter-regional signal processing will allow me to address my next goal: to apply pharmacological, electrophyiosological and genetic tools to treat memory and movement disorders. The cellular response to cholinergic and dopaminergic neurotransmitters in the hippocampal region is largely explored, but little is known about the optimising effect of extrinsic manipulation of the neuromodulatory projections on the encoding properties of hippocampal neurons and mnemonic function of the limbic system. Therefore, the present proposal addresses two broad questions: 1) Can we enhance the hippocampal spatial representation by activation of the cholinergic/dopaminergic systems? 2) Should medial temporal lobe amnesia and depression be regarded as independent syndromes, or are they interlinked?