Dopaminergic neuromodulation of memory and behaviour: implications in aging. (360G-Wellcome-088286_Z_09_Z)

Structural and functional MRI (fMRI) has demonstrated that age-related memory decline is characterized by changes in medial temporal lobe and prefrontal structures. Recently it has been recognized that molecular mechanisms involving specific neurotransmitters, such as dopamine, are also affected in aging. Dopamine is released by neurons in the substantia nigra/ventral tegmental area (SN/VTA) of the midbrain and plays a critical role in the long-term consolidation of memories in the medial tempor al lobes. However, to date there is little quantitative in vivo data available on how structural parameters of the SN/VTA and dopamine neuromodulation relate to memory performance in older adults, and to consolidation in particular. I wish to test a hypothesis that decrements in dopaminergic neurotransmission have a quantitative relationship to impaired memory consolidation, reward-related enhancement of memory and altered reward-based choice behavior in aging. To achieve this I will study 30 healthy elderly subjects who will undergo clinical and behavioural assessment, high resolution structural MRI and fMRI using a memory consolidation and reward learning task paradigm. I will combine these measures with pharmacological manipulation of dopaminergic neurotransmission. This integrative approach will allow bridging of clinical phenotypes and structural/functional imaging and pharmacology, to further characterise age-related cognitive and behavioural impairments.