CORTICAL SUBSTRATES OF WORKING MEMORY FOR VISUAL MOTION

描述（由申请人提供）：前额叶皮层（PFC）在执行功能中起重要作用，并与感觉工作记忆和注意力有关。在精神分裂症和其他精神疾病中发现的认知功能障碍与PFC功能障碍有关，因此，了解PFC中调节认知功能的功能电路对精神疾病的研究具有重要意义。尽管有证据表明PFC对感觉皮层的影响对认知功能很重要，但这种影响的性质仍然知之甚少。为了理解这些影响，确定PFC如何表示它从感觉神经元接收到的信号是很重要的。为了研究这个问题，我们选择了涉及视觉运动的任务，因为它的神经编码和运动处理皮层区域已经被详细研究过。我们的目标是表征PFC中视觉运动的表征，并检查它对运动处理区域MT的自上而下的影响。在过去的资助期间，我们发现在中央凹，大多数PFC神经元表现出方向选择（DS）反应，这表明它们的MT起源。我们还描述了与这些刺激相关的任务分配电路，并详细描述了其神经元携带的记忆相关信号。我们现在检查PFC中跨空间的运动表征是否反映了来自两个半球mt的自下而上运动信号的局部性质（目的1）。这一信息对于PFC解释出现在视野不同部分的感觉信号的方式及其对高度视网膜变性和刺激选择性MT神经元的自上而下影响具有重要意义。我们将使用PFC的可逆失活来确定其在运动任务记忆的所有组成部分中对MT神经元活动的影响（目标2）及其对这些任务的行为表现的贡献（目标3）。当猴子在对侧和同侧半球内比较两个连续运动刺激的方向或速度时，我们将记录脉冲活动和局部场电位，以测量运动阈值。这些研究将为PFC在工作记忆任务中表现和控制感官信号的方式提供新的信息。该结果将对阐明精神分裂症认知功能障碍的基础具有重要意义，认知功能障碍长期与感觉工作记忆缺陷和前额叶功能受损有关。

DESCRIPTION (provided by applicant): The prefrontal cortex (PFC) plays an important role in executive function and has been implicated in sensory working memory and attention. The cognitive dysfunctions found in schizophrenia and other mental disorders has been linked to the dysfunction of PFC, and thus, understanding the functional circuitry that mediates cognitive function in PFC is of major relevance to the study of mental illness. In spite of the evidence that the influence of PFC on sensory cortex is important for cognitive function, the nature of this influence is still poorly understood. To understand such influences it is important to determine how PFC represents signals it receives from sensory neurons. To examine this problem we chose tasks involving visual motion since its neural code and motion processing cortical areas have been examined in some detail. Our goal is to characterize the representation of visual motion in the PFC and to examine the top-down influences it provides to motion processing area MT. During the past grant period we showed that at the fovea the majority of the PFC neurons show direction selective (DS) responses, suggesting their MT origins. We also characterized the circuitry involved in assigning task relevance to such stimuli and characterized in detail memory-related signals its neurons carry. We now examine whether the representation of motion in the PFC across space reflects the local nature of the bottom-up motion signals arriving from MTs in both hemispheres (Aim #1). This information has important implications for the way the PFC interprets sensory signals appearing in different portions of the visual field and for its top-down influences on the highly retinotopic and stimulus selective MT neurons. We will use reversible inactivation of the PFC to determine its influence on activity of MT neurons during all components of memory for motion tasks (Aim #2) and its contribution to behavioral performance of these tasks (Aim #3). We will record spiking activity and local field potentials as measure motion thresholds while monkeys compare directions or speeds of two sequential moving stimuli presented within and between contralateral and ipsilateral hemifields. These studies will provide new information about the way PFC represents and controls sensory signals used during working memory tasks. The results will have important implications for elucidating the basis of cognitive dysfunction in schizophrenia, long associated with deficits in sensory working memory and impaired prefrontal function.