Goldman-Rakic P S
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13473-80. doi: 10.1073/pnas.93.24.13473.
This chapter recounts efforts to dissect the cellular and circuit basis of a memory system in the primate cortex with the goal of extending the insights gained from the study of normal brain organization in animal models to an understanding of human cognition and related memory disorders. Primates and humans have developed an extraordinary capacity to process information "on line," a capacity that is widely considered to underlay comprehension, thinking, and so-called executive functions. Understanding the interactions between the major cellular constituents of cortical circuits-pyramidal and nonpyramidal cells-is considered a necessary step in unraveling the cellular mechanisms subserving working memory mechanisms and, ultimately, cognitive processes. Evidence from a variety of sources is accumulating to indicate that dopamine has a major role in regulating the excitability of the cortical circuitry upon which the working memory function of prefrontal cortex depends. Here, I describe several direct and indirect intercellular mechanisms for modulating working memory function in prefrontal cortex based on the localization of dopamine receptors on the distal dendrites and spines of pyramidal cells and on interneurons in the prefrontal cortex. Interactions between monoamines and a compromised cortical circuitry may hold the key to understanding the variety of memory disorders associated with aging and disease.
本章叙述了剖析灵长类动物大脑皮层记忆系统的细胞和回路基础的研究工作，目的是将从动物模型中正常脑组织研究获得的见解扩展到对人类认知及相关记忆障碍的理解。灵长类动物和人类已发展出非凡的“在线”信息处理能力，这种能力被广泛认为是理解、思考及所谓执行功能的基础。理解皮层回路主要细胞成分（锥体细胞和非锥体细胞）之间的相互作用，被视为阐明支持工作记忆机制乃至认知过程的细胞机制的必要步骤。来自各种来源的证据不断积累，表明多巴胺在调节前额叶皮层工作记忆功能所依赖的皮层回路兴奋性方面起主要作用。在此，我描述了几种基于多巴胺受体在前额叶皮层锥体细胞远端树突和棘以及中间神经元上的定位来调节前额叶皮层工作记忆功能的直接和间接细胞间机制。单胺类物质与受损皮层回路之间的相互作用可能是理解与衰老和疾病相关的各种记忆障碍的关键。
