NEURAL CIRCUIT OF WORKING MEMORY IN THE NON-HUMAN PRIMATE

我们的长期目标是在单个神经元的水平上提高我们对工作记忆的理解，并利用这些信息开发一个非人类灵长类工作记忆中断模型，这将有助于揭示精神分裂症认知缺陷的神经基础。精神分裂症患者在背外侧前额叶皮质和丘脑出现结构异常，这可能与他们的工作记忆缺陷有关。我们建议使用已建立的和新的技术来研究这些区域和其他区域的正常和被破坏的工作记忆功能。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确定参与工作记忆的神经回路，并提供与类似人类数据进行比较的基础；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；我们将使用一种新的电刺激微刺激范式来干扰特定背景下的工作记忆任务中前额皮质和丘脑的功能，以便在单个神经元水平上探索工作记忆的结构。通过比较动物的S表现和精神分裂症患者的表现，我们将进一步理解靶区在调节患者工作记忆缺陷中的作用。 我们对靶区的选择是以解剖学数据为指导的，这些数据探索了人类精神分裂症患者的结构性缺陷。我们的实验设计正在并将继续受到研究结果的影响，该发现使用行为和成像技术来研究患者的工作记忆缺陷。一旦我们的模型建立，我们将直接比较患者的行为与我们的模型在相同任务条件下的行为。总而言之，我们相信，我们将神经生理学、神经成像和行为技术与跨物种比较相结合的策略将显著促进我们对工作记忆和精神分裂症的神经基础的理解。

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.