Dash Pramod K, Moore Anthony N, Kobori Nobuhide, Runyan Jason D
The Vivian L. Smith Center for Neurologic Research, and Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, USA.
Learn Mem. 2007 Aug 9;14(8):554-63. doi: 10.1101/lm.558707. Print 2007 Aug.
The prefrontal cortex is necessary for directing thought and planning action. Working memory, the active, transient maintenance of information in mind for subsequent monitoring and manipulation, lies at the core of many simple, as well as high-level, cognitive functions. Working memory has been shown to be compromised in a number of neurological and psychiatric conditions and may contribute to the behavioral and cognitive deficits associated with these disorders. It has been theorized that working memory depends upon reverberating circuits within the prefrontal cortex and other cortical areas. However, recent work indicates that intracellular signals and protein dephosphorylation are critical for working memory. The present article will review recent research into the involvement of the modulatory neurotransmitters and their receptors in working memory. The intracellular signaling pathways activated by these receptors and evidence that indicates a role for G(q)-initiated PI-PLC and calcium-dependent protein phosphatase calcineurin activity in working memory will be discussed. Additionally, the negative influence of calcium- and cAMP-dependent protein kinase (i.e., calcium/calmodulin-dependent protein kinase II (CaMKII), calcium/diacylglycerol-activated protein kinase C (PKC), and cAMP-dependent protein kinase A (PKA)) activities on working memory will be reviewed. The implications of these experimental findings on the observed inverted-U relationship between D(1) receptor stimulation and working memory, as well as age-associated working memory dysfunction, will be presented. Finally, we will discuss considerations for the development of clinical treatments for working memory disorders.
前额叶皮质对于引导思维和规划行动至关重要。工作记忆是信息在脑海中的主动、短暂维持，以便后续监测和操作，它是许多简单及高级认知功能的核心。研究表明，在多种神经和精神疾病中工作记忆会受损，且可能导致与这些疾病相关的行为和认知缺陷。理论上认为，工作记忆依赖于前额叶皮质及其他皮质区域内的回响回路。然而，最近的研究表明，细胞内信号和蛋白质去磷酸化对工作记忆至关重要。本文将综述关于调节性神经递质及其受体参与工作记忆的最新研究。将讨论这些受体激活的细胞内信号通路，以及表明G(q)起始的磷脂酰肌醇-磷脂酶C（PI-PLC）和钙依赖性蛋白磷酸酶钙调神经磷酸酶活性在工作记忆中起作用的证据。此外，还将综述钙依赖性和环磷酸腺苷（cAMP）依赖性蛋白激酶（即钙/钙调蛋白依赖性蛋白激酶II（CaMKII）、钙/二酰基甘油激活的蛋白激酶C（PKC）和cAMP依赖性蛋白激酶A（PKA））活性对工作记忆的负面影响。将介绍这些实验结果对观察到的D(1)受体刺激与工作记忆之间的倒U形关系以及与年龄相关的工作记忆功能障碍的影响。最后，我们将讨论针对工作记忆障碍开发临床治疗方法时的注意事项。
