Studies in humans and animals show that dopaminergic neuromodulation originating from the substantia nigra/ventral tegmental area (SN/VTA) of the midbrain enhances hippocampal synaptic plasticity for novel events and has a motivationally energizing effect on actions through striatal mechanisms. In this review, we discuss how these mechanisms of dopaminergic neuromodulation connect to the behavioural and functional consequences that age-related structural degeneration of the SN/VTA exerts on declarative memory. We propose a framework called 'NOvelty-related Motivation of Anticipation and exploration by Dopamine' (NOMAD) which captures existing links between novelty, dopamine, long-term memory, plasticity, energization and their relation to aging. We propose that maximizing the use of this mechanism by maintaining mobility and exploration of novel environments could be a potential mechanism to slow age-related decline of memory.
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