NEURONAL MECHANISMS OF COGNITION

这个项目的长期目标是阐明细胞和 前额叶皮质参与的突起的电路基础 工作记忆。有关工作将透过以下两方面的调查进行： 工作记忆领域的范围，以及(B)神经调节 使用单电池记录法的参与本地电路 在经过训练的猴子身上。该中心以前的工作，使用动眼神经版本 空间延迟反应任务的研究表明，神经元在 背外侧前额叶皮质可以保持视觉空间信息。 在任务的延迟期内，行“”会持续许多秒。我们建议 为了将我们对工作记忆系统的知识扩展到物体和 信息处理的听觉领域，因为这些领域特别 与精神分裂症有关。我们将在工作进展的基础上，进一步 描述物体底层电路的神经元元件 刺激属性(颜色、形状、图案)的认知 编码在工作内存中。此外，我们还将开始调查 工作记忆在听觉领域的神经机制，这与 对人类对语言和思维的理解，一种无序的 可能导致“松散关联”的语义无政府状态。 第二个主要目标是开始分析前和 猕猴前额叶神经回路的突触后调制 延迟响应任务。根据我们的发现，D1拮抗剂 损害工作记忆，我们将深入探讨多巴胺的作用 受体在这一功能中的调节作用。鉴于最近的 不同多巴胺受体的分子生物学鉴定 亚型，一系列选择性拮抗剂将用于离子导入 功能分类神经元的研究。之间的相互作用 多巴胺受体功能及其兴奋性和抑制性 氨基酸，以及胆碱能传递将在 细节。将研究α肾上腺素受体的作用以进行比较 在功能上。确定…的动态(阶段性作用与主动性作用) 儿茶酚胺在诱导或维持延迟- 期间的活动，我们打算实时检查关系， 延迟反应中递质释放与神经元活动之间的关系 任务，使用电化学检测。这些研究预计将 提供对神经生物学、神经化学和 工作记忆过程的神经解剖学基础，从而导致 对精神分裂症等患者思维过程障碍的认识 精神错乱。

The long-term objective of this project is to elucidate the cellular and circuit basis of processes in prefrontal cortex which are involved in working memory. This will be achieved by investigation of both: (a) the scope of working memory domains, and (B) the neuromodulation of participating local circuits using the method of single-cell recording in trained monkeys. Prior work at this Center, using oculomotor versions of the spatial delayed-response task, has shown that neurons in dorsolateral prefrontal cortex can hold visuospatial information "on- line"" for many seconds during the delay period of the task. We propose to extend our knowledge of working memory systems to the object and auditory domains of information processing as these are particularly relevant to schizophrenia. We will build on working progress to further characterize the neuronal elements of a circuit underlying object cognition in which stimulus attributes (colors, shapes, patterns) are encoded in working memory. In addition we will begin to investigate neural mechanisms of working memory in the auditory domain, which relates to the human comprehension of language and thought, a disorder of which could lead to the semantic anarchy of "loose associations". The second major objective is to begin the analysis of pre- and postsynaptic modulation of prefrontal circuits in monkeys performing delayed-response tasks. Following on our discovery that D1 antagonists impair working memory, we will explore in depth the role of dopamine receptor modulation in this function. In the light of the recent molecular biological identification of distinct dopamine receptor subtypes, a range of selective antagonists will be used in iontophoretic studies of functionally classified neurons. Interactions between dopamine receptor function and that of the excitatory and inhibitory amino acids, as well as cholinergic transmission will be examined in detail. Alpha adrenoreceptor actions will be investigated for comparison in function. To determine the dynamics (phasic versus tonic actions) of catecholamine function in either the induction or maintenance of delay- period activity, we intend to examine the relationship, in real-time, between transmitter release and neuronal activity during delayed-response tasks, using electrochemical detection. These studies are expected to provide insight into the neurobiological, neurochemical and neuroanatomical basis of working memory processes and thereby lead to an understanding of disordered thought processes in schizophrenia and other mental disorders.