INTERVAL TIMING BEHAVIOR--ENSEMBLE RECORDING/STIMULANTS

以前的工作已经证明了内部时钟之间的关系 用于持续时间感知和增强率。因此，完整的 理解感知事件持续时间因以下原因而发生的变化 精神刺激剂的使用，以及其背后的机制 变化，是形成成功战略的关键 预防和治疗药物滥用。目前的提案旨在 了解精神刺激剂诱导的神经机制 间隔计时中的知觉变化。这将通过以下方式实现 多个神经元的同时细胞外记录 大脑核团，在大鼠中，断断续续地服用精神刺激剂(例如， 甲基苯丙胺和可卡因)，同时在临时制作中表演 任务。实验1研究了神经的时空模式。 在黑质致密部内的计时行为中进行放电， 尾壳核和内侧前额叶皮质(据信是 持续时间感知)。神经活动模式的变化，以前 在服用兴奋剂后，将与观察到的行为相匹配 改变。实验2被设计用来研究动态变化 慢性服用兴奋剂时的神经放电模式。 以前的工作已经展示了时间变化的特定模式 长期服用兴奋剂时的知觉，定性的 类似于对慢性戒断后耐受性的描述 兴奋剂。利用不同的途径慢性冰毒和 可卡因持续给药与间歇给药相比， 行为和药效学敏化和耐受性 被操纵了。在此期间对假设的定时电路的集合记录 这一进展将使对潜在机制的研究成为可能 导致了这些变化。查找更改之间的特定关系 随着时间的推移，知觉和慢性刺激剂诱导的耐受性将被牵连 使用旨在按顺序改变持续时间记忆的治疗策略 为了对抗这些兴奋剂诱导的知觉变化的影响 时间到了。

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.