Memory and The Ageing Brain
: Dopamine, sleep and the hippocampus

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Human brains selectively store knowledge about the world to optimise future behaviour. We automatically rehearse and contextualise, or discard information to create a robust collection of facts and events. The medial temporal lobe is central to a network of memory regions within the brain that select important memories for long term storage. Much of this memory selection is purported to occur automatically during sleep. Recent emerging data have suggested that dopamine might influence memory longevity. However, it has not been clear at which time point in the memory process dopamine is active, particularly whether dopamine biases memory at the time information is encountered or, later, during consolidation of memory during sleep.
In two independent double-blind randomised placebo-controlled studies of healthy older adults, I administered dopamine to temporally target memory evolution at different time-points in relation to learning using a verbal recognition task. Nocturnal dopamine enhanced efficiency of routine forgetting while sparing saliently tagged information. Importantly, dopamine administration did not affect encoding or retrieval, strongly suggesting that dopamine acts after encoding during memory storage processes. Analysis of polysomnography suggested that the behavioural tagging effect of dopamine was associated with increased spindle amplitude during slow wave sleep. Overnight dopamine also increased total slow wave sleep duration by 11%. No relationships were seen between memory and medial temporal lobe structures on structural MRI. However, volumes of hippocampal subfields CA2 and dentate gyrus and entorhinal cortex were all associated with slow wave sleep duration. Intriguingly, CA2 volume negatively correlated with slow wave sleep duration, but positively correlated with spindle density.
In summary, nocturnal dopamine optimises the memory selection processes by modulating slow wave spindles.
Date of Award24 Mar 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorE J Coulthard (Supervisor), Risto Kauppinen (Supervisor) & Matt W Jones (Supervisor)

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