NEURAL CIRCUIT OF WORKING MEMORY IN NON-HUMAN PRIMATE

非人类灵长类动物工作记忆的神经回路

• 批准号: 6969032
• 负责人: LAWRENCE H SNYDER
• 金额: $ 22.36万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-28 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969032
• 关键词: Macaca; behavioral /social science research tag; brain electrical activity; brain mapping; cognition disorders; disease /disorder model; electrostimulus; functional magnetic resonance imaging; memory disorders; model design /development; neuropsychological tests; prefrontal lobe /cortex; pulvinar thalami; schizophrenia; short term memory; single cell analysis; thalamus

Our long range goal is to improve our understanding of working memory at the level of individual neurons, and to use this information to develop a model of non-human primate model of disrupted working memory that will shed light on the neural basis of the cognitive deficits in schizophrenia. Schizophrenia patients show structural abnormalities in the dorsolateral prefrontal cortex and the thalamus that may be related to their deficits in working memory. We propose to use both established and novel techniques to investigate normal and disrupted working memory function in these and other areas. In particular, we will use whole-brain functional magnetic resonance imaging in the non-human primate to identify neural circuits involved in working memory and to provide a basis for comparison with analogous human data; we will use single neuron recording in the pulvinar nucleus of the thalamus to characterize its role in working memory; and we will use a novel electrical microstimulation paradigm to disrupt function in prefrontal cortex and thalamus during a context-specific working memory task in order to probe the structure of working memory at a single neuron level. By comparing the animal' s performance with that of schizophrenia patients, we will further our understanding of the role that the targeted areas play in mediating the working memory deficits of the patients. Our choice of target areas is guided by the anatomical data of which explores structural deficits in human schizophrenia patients. Our experimental design is and will continue to be informed by findings , which uses behavioral and imaging techniques to study working memory deficits in patients. Once our model is established, we will directly compare patient behavior with that of our model under identical task conditions. In summary, we believe that our strategy of combining neurophysiological, neuroimaging and behavioral techniques with cross-species comparisons will significantly advance our understanding of the neural bases of both working memory and schizophrenia.

我们的长期目标是提高我们在单个神经元水平上对工作记忆的理解，并利用这些信息开发一个非人类灵长类动物工作记忆中断模型，这将揭示精神分裂症认知缺陷的神经基础。精神分裂症患者表现出背外侧前额叶皮层和丘脑的结构异常，这可能与他们的工作记忆缺陷有关。我们建议使用现有的和新的技术来研究这些和其他区域的正常和中断的工作记忆功能。特别是，我们将在非人类灵长类动物中使用全脑功能磁共振成像来识别参与工作记忆的神经回路，并为与类似的人类数据进行比较提供基础；我们将使用丘脑枕核的单个神经元记录来表征其在工作记忆中的作用；为了在单个神经元水平上探索工作记忆的结构，我们将使用一种新的电微刺激范式来破坏情境特定工作记忆任务中前额叶皮层和丘脑的功能。通过比较动物与精神分裂症患者的表现，我们将进一步了解目标区域在调节患者工作记忆缺陷中的作用。