Keeping track of things: Forming associations between temporally separated events

当事件之间有时间间隔时，我们在学习和后来的记忆中就不太能把它们联系起来。因此，要追踪那些实际上可能有因果关系的事物就变得更加困难了，例如，要知道即使遥远的发动机噪音也能预测未来的危险，或者根据原料的气味来预测晚餐。众所周知，成功地跨越事件之间的时间间隔的能力会随着年龄的增长而退化。该项目将研究这一重要认知能力的大脑基础及其心理基础。一种可能性是，第一个事件的心理形象在产生关联之前就消失了。另一种可能性是其他干预事件干扰了第一个事件和结果事件之间的关联。时间与干扰的不同作用将在实验中进行检验，该实验系统地比较了第一个事件结束和结果事件开始之间的时间间隔如何减少学习，相对于在结果事件开始之前不终止的持续时间较长的事件所产生的学习减少（这样，要桥接的总时间长度是相等的）。在第一种情况下，竞争事件干扰条件反射的可能性要大得多。这些实验将在老鼠身上进行，使用高度控制的事件呈现，比如一种独特的噪音，然后是轻微的足部电击。由于这种受控实验研究中呈现的“事件”在某种程度上是人为的（例如，纯音刺激），我们还将测试同样的干预在大脑中对三维物体识别的影响。在一系列补充的实验中，我们将在熟悉度测试前有或没有时间延迟地呈现物体，有或没有中间物体的呈现。大脑干预将精确地针对与这些过程有关的皮层和皮层下区域。目前的项目将在之前的研究成果的基础上进一步发展，我们将通过在特定途径中消耗大脑化学物质和靶向药物递送来选择性地干扰这些途径中的化学信号。在实验计划的同时，我们将访问学校，并利用六年级的外展计划来解释这类动物工作的重要性。一旦我们确定了通道内耗竭产生缺陷的心理基础，我们将与制药行业的联系人接触，以确保我们通过最适当的药物测试跟踪最重要的发现。

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.