REPRESENTATION OF TEMPORAL INFORMATION

时间信息的表示

• 批准号: 7232303
• 负责人: CATALIN V. BUHUSI
• 金额: $ 18.24万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-15 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7232303
• 关键词: Address; Animal Model; Behavior; Behavior Control; Behavioral; Behavioral Model; Biological Neural Networks; Code; Cognitive; Computer Simulation; Corpus striatum structure; Data; Decision Making; Disease; Disruption; Dorsal; Electrodes; Electrophysiology (science); Elements; Hippocampus (Brain); Huntington Disease; Image; Infusion procedures; Modeling; Operative Surgical Procedures; Parkinson Disease; Patients; Pattern; Process; Range; Rate; Rattus; Reproduction; Research; Research Personnel; Role; Schizophrenia; Signal Transduction; Site; Substantia nigra structure; Tetrodotoxin; Time; behavior measurement; classical conditioning; frontal lobe; relating to nervous system; research study; time interval; time use

DESCRIPTION (provided by applicant): Fundamental processes such as associative learning, rate calculation and decision making crucially rely on estimation and reproduction of time intervals. These processes are disrupted in Parkinson's disease, Huntington's disease, and Schizophrenia. This project will further our understanding of the disruptions of cognitive processes in these disorders by investigating neural activity in the neural substrates showed by imaging studies to be dysregulated in these disorders. The major objective of this proposal is to study the neural representation of temporal information in the seconds-to-minutes range using a multi-level approach involving electrophysiology, behavior, and computational modeling. The neural representation of temporal information will be investigated by multi-site, multi-electrode neural recordings; the behavioral representation of time will be examined in freely behaving rats performing interval timing tasks; the computational elements and operations required to perform these behavioral tasks will be investigated by computer modeling. First, at the electrophysiology level, the investigator will examine the neural representation of temporal information by multi-site, ensemble recordings in a network of substrates including striatum, frontal cortex, substantia nigra, and the hippocampus in freely behaving normal rats as well as in rats in which some of these substrates are temporarily inactivated. Notably, from the couple of electrophysiological studies currently addressing the substrates of interval timing, one was performed by our research group. Second, rats' behavior will be examined while performing two behavioral tasks (involving time estimation and reproduction) in which Parkinson, Huntington, and Schizophrenic patients are known to be impaired. Third, at the computational level the investigator will study a biologically plausible model of interval timing and will compare the predictions of the model with data collected in the behavioral studies. The project will help elucidate the behavioral and neural coding of time, and our understanding of the role of specific neural substrates in disorders like Parkinson, Huntington, and Schizophrenia. The results of the project can be used to devise behavioral measures for the early assessment of such disorders, and to understand the cognitive processes disrupted when these substrates are dysfunctional. This information is crucial to assessing the value/efficiency of potential treatment strategies in animal models of such disorders.

描述（由申请人提供）：诸如联想学习、速率计算和决策等基本过程至关重要地依赖于时间间隔的估计和再现。这些过程在帕金森病、亨廷顿病和精神分裂症中被破坏。该项目将通过研究成像研究显示的在这些疾病中失调的神经基质中的神经活动，进一步加深我们对这些疾病中认知过程中断的理解。本提案的主要目的是研究时间信息在秒到分钟范围内的神经表征，使用涉及电生理学，行为和计算建模的多层次方法。时间信息的神经表征将通过多位点、多电极神经记录进行研究；时间的行为表征将在执行间隔计时任务的自由行为大鼠中进行检验；执行这些行为任务所需的计算元素和操作将通过计算机建模进行研究。首先，在电生理学水平上，研究者将在行为自由的正常大鼠以及其中一些底物暂时失活的大鼠中，通过纹状体、额叶皮层、黑质和海马体等底物网络中的多位点、整体记录来检查时间信息的神经表征。值得注意的是，从目前解决间隔时间基础的一对电生理学研究中，我们的研究小组进行了一项研究。其次，在帕金森、亨廷顿和精神分裂症患者被认为受损的两项行为任务（包括时间估计和繁殖）中，将检查大鼠的行为。第三，在计算层面，研究者将研究一个生物学上合理的间隔时间模型，并将该模型的预测与行为研究中收集的数据进行比较。该项目将有助于阐明时间的行为和神经编码，以及我们对帕金森、亨廷顿和精神分裂症等疾病中特定神经基质作用的理解。该项目的结果可用于设计早期评估此类疾病的行为措施，并了解当这些基底功能失调时认知过程被破坏。这一信息对于评估此类疾病动物模型中潜在治疗策略的价值/效率至关重要。