Keeping track of things: Forming associations between temporally separated events

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When there is a time gap between events, we are less able to make a connection between them in learning and later memory. Thus it is harder to keep track of things that could in fact be causally related, in order - for example - to know that even distant engine noise can predict a future hazard or to anticipate dinner based on the smell of raw ingredients. The ability successfully to bridge a time gap between events is known to deteriorate with age. This project will investigate the underpinning brain substrates of this important cognitive ability in relation to its psychological bases. One possibility is that the mental image of the first event fades before the association at issue can be made. An alternative possibility is that other intervening events interfere with the association between the first event and the outcome event. The differential role of time versus interference will be examined in experiments which systematically compare how learning is reduced by a time gap between the end of the first event and the start of the outcome event, relative to the reduction in learning produced by events of extended duration which do not terminate before the start of the outcome event (such that the overall time duration to be bridged is equivalent). In the first scenario the potential for competing events to interfere with conditioning is much greater. These experiments will be conducted on rats using highly controlled presentation of events such as a distinctive noise followed by a mild foot shock. Because the 'events' presented in such controlled experimental studies are somewhat artificial (e.g., a pure tone stimulus) we will also test the effects of the same interventions in the brain on the recognition of three-dimensional objects. In a complementary series of experiments we will present the objects with and without a time delay before familiarity is tested, with and without the presentation of intervening objects.The brain interventions will be precisely targeted in both cortical and sub-cortical areas implicated in these processes. The present project will advance on previous findings in that we will selectively interfere with chemical signalling within these pathways, both by depleting brain chemicals in specific pathways and by targeted drug delivery.In parallel with the experimental programme, we will visit schools and use sixth form outreach programmes to explain the importance of animal work of this kind. Once we have identified the psychological bases of deficits produced by depletion within a pathway, we will engage with contacts in the pharmaceutical industry to ensure that we follow-up on the most important findings with the most appropriate drug tests.