INTERVAL TIMING BEHAVIOR--ENSEMBLE RECORDING/STIMULANTS

以前的工作已经证明了内部时钟 用于持续时间感知和强化率。 因此，一个完整的 理解由于以下原因导致的感知事件持续时间的变化 精神兴奋剂的管理，以及这些机制的基础 变化，是形成成功的战略， 预防和治疗药物滥用。 目前的建议旨在 了解精神兴奋剂诱导的神经机制 间隔时间的感知变化。 这将通过 多个神经元的同时细胞外记录， 脑核，在大鼠中开和关和关精神兴奋剂（例如， 甲基苯丙胺和可卡因），同时进行临时生产 任务 实验1研究了神经元的时空模式 在黑质内的定时行为期间放电， 尾壳核和内侧前额叶皮层（据信是 持续时间感知）。 神经活动模式的变化， 在给予兴奋剂后，将与观察到的行为相匹配， 变化 实验2旨在研究 在慢性兴奋剂管理过程中的神经放电模式。 以前的工作已经证明了一个特定的模式的变化，在时间 在慢性兴奋剂给药期间的感知， 类似于从慢性戒断后耐受性的描述 兴奋剂 利用慢性甲基苯丙胺的不同途径， 可卡因给药：连续vs.间歇， 行为和药效学致敏，耐受性可以是 被操纵了 假设的定时电路的封闭记录， 这一进展将有助于研究潜在的机制， 导致这些变化。 查找更改之间的特定关系 在时间知觉和慢性刺激诱导的耐受性将牵连 使用旨在改变持续记忆的治疗策略， 为了对抗这些刺激引起的感知变化的影响， 时间

Previous work has demonstrated a relationship between the internal clock used for duration perception and reinforcement rate. As such, a full understanding of the changes in perceived event duration due to psychostimulant administration, as well as the mechanisms underlying these changes, are crucial to the formation of successful strategies of prevention and treatment of drug abuse. The current proposal seeks to understand the neural mechanisms underlying psychostimulant-induced perceptual changes in interval timing. This will be accomplished by simultaneous extracellular recording of multiple neurons, in multiple brain nuclei, in a rat on and off and off psychostimulants (e.g., methamphetamine and cocaine) while performing in a temporal-production task. Experiment 1 investigates the spatiotemporal patterns of neural firing during timing behavior within the substantia nigra pars compacta, caudate-putamen, and medial prefrontal cortex (areas believed to underlie duration perception). The changes in neural activity patterns, before and after stimulant administration, will be matched to observed behavioral changes. Experimetn 2 is designed to investigate the dynamic changes in the neural firing patterns during chronic stimulant administration. Previous work has demonstrated a specific pattern of changes in temporal perception during chronic stimulant administration which is qualitatively similar to descriptions of tolerance following withdrawal from chronic stimulants. Utilizing differing routes of chronic methamphetamine and cocaine administration: continuous vs. intermittent, the development of behavioral and pharmacodynamic sensitization an tolerance can be manipulated. Ensemble recording of the hypothesized timing circuit during this development will allow investigation of the underlying mechanisms causing these changes. Finding a specific relationship between changes in time perception and chronic stimulant-induced tolerance will implicate the use of treatment strategies designed to alter duration memory in order to counter the effects of these stimulant-induced changes in perceived time.