Synthesis of Incongruent Temporal Information

描述（由申请人提供）：对时间的感知使个体能够适应环境事件的时间规律。它也在我们做出的选择中起着直接的作用。延迟折扣指的是一种潜在商品（如货币、药品、食品）的主观价值随着获得该商品的预期延迟而下降，许多实验已经证明，人们“非理性”地倾向于在较短的延迟中获得小奖励，而不是在较长的延迟中获得大奖励。有药物滥用问题的个体对药物的折扣率有所不同，这被认为是导致短视选择吸毒的原因。重要的是，折现率的变化可以理解为由于药物引起的时间感知和时间记忆的改变而导致的时间期望的变化。具体地说，一些滥用的药物，包括精神兴奋剂和致幻剂，改变了对时间的感知。该项目的总体假设是，当产生时间预期时，与药物状态相关的记忆与无药物状态相结合。这些综合的时间预期会导致可能选择的预期价值的改变（由于它们对折扣的影响），并可能导致“冲动”行为，如吸毒。我们最近报道，用两种成分提示训练的大鼠，每一种成分提示在不同的时间间隔后（例如，声音= 10秒，光线= 20秒），将证明，当同时提供复合提示（声音+光线）时，它们平均在这些时间（15秒）内期待食物。我们把这种现象称为不一致时间信息的合成（SITI）。与本项目特别相关的是，我们最近也证明了时间记忆合成可以在药物状态下发生。具体来说，大鼠被训练为在生理盐水（0.5 mg/kg）后10秒预期食物供应，而在安非他明（0.5 mg/kg）后20秒预期食物供应，在没有反馈的情况下，在中等剂量安非他明（0.25 mg/kg）后进行测试时，大鼠表现出15秒的时间预期。这些数据表明，与不同药物状态相关的记忆可以在检索时组合在一起，产生不适应的时间期望。关于药物状态下时间记忆合成的本质，以及在没有药物的受试者中促进SITI的条件，仍然存在许多问题。本申请旨在研究药物状态相关时间记忆的合成（目标1），研究与激励值相关的条件，这些条件似乎可以调节SITI的发生率（目标2），开发允许在偏好/选择中调查SITI的程序（目标3），并研究一个与药物诱导的时间记忆抽样中预期改变有关的新假设。这里提出的工作具有重要的潜力，可以增加我们对药物使用可能影响选择的时间预期的理解。

DESCRIPTION (provided by applicant): The perception of time allows individuals to adapt to the temporal regularities of environmental events. It also plays a direct role in the choices we make. Delay discounting refers to the decrease in subjective value of a potential commodity (e.g., money, drugs, food) as a function of the expected delay until acquisition of that commodity, and numerous experiments have demonstrated "irrational" preference for the receipt of a small reward at a shorter delay over a larger reward at a longer delay. The rate of discounting has been shown to differ in individuals with substance abuse problems, and is thought to contribute to the short-sighted choice to take drugs. Importantly, changes in discounting rate can be understood as resulting from changes in temporal expectation, as a consequence of drug-induced alterations in temporal perception and temporal memory. Specifically, it has been shown that a number of abused drugs, including both psychostimulants and hallucinogenics, alter the perception of time. The global hypothesis underlying the proposed project is that memories associated with drug-present states are combined with drug-free memories when generating temporal expectations. These synthesized temporal expectations would then lead to alterations in anticipated value of possible choices (due to their impact on discounting), and may contribute to "impulsive" behaviors such as drug use. We have recently reported that rats trained with two component cues that each indicate food availability after a different interval has elapsed (e.g., tone = 10 sec and light = 20 sec) will demonstrate that they expect food at the average of these times (15s) when presented with the simultaneous compound cue (tone + light). We refer to this phenomenon as the synthesis of incongruent temporal information (SITI). Of particular relevance to the present project, we have also recently demonstrated that temporal memory synthesis can occur across drug states. Specifically, rats trained to expect food availability at 10s following saline adminstration, but 20s following amphetamine administration (0.5 mg/kg) will demonstrate temporal expectancy at 15s when tested, without feedback, following an intermediate dose of amphetamine (0.25 mg/kg). These data indicate that the memories associated with different drug states can be combined at retrieval to generate temporal expectancies that are maladaptive. Numerous questions remain about the nature of temporal memory synthesis across drug-states, as well as the conditions that promote SITI in drug naove subjects. The present application seeks to investigate the synthesis of drug state-associated temporal memories (Aim 1), investigate conditions related to incentive value that appear to moderate the incidence of SITI (Aim 2), develop procedures allowing an investigation of SITI in preference/choice (Aim 3), and investigate a novel hypothesis related to altered expectation due to drug-induced bias in temporal memory sampling. The work proposed here has significant potential to increase our understanding of the temporal expectations resulting from drug use that may influencing choice. PUBLIC HEALTH RELEVANCE: Temporal expectations are at the heart of delay discounting (the decrease in anticipated value of a commodity as a function of the expected delay until its receipt), and both temporal perception and the rate of delay discounting have been shown to be altered following acute and chronic drug use. We have shown that temporal memories formed during drug use can be averaged with temporal memories formed in drug-free states, and hypothesize that these combinatorial, maladaptive expectations will impact choice via their influence on anticipated value. The current project examines temporal memory synthesis across drug states, and the involvement of memory synthesis in choice behavior.