Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
Behav Brain Res. 2011 Dec 1;225(2):610-22. doi: 10.1016/j.bbr.2011.08.016. Epub 2011 Aug 22.
Working memory is a highly heritable complex cognitive trait that is critical for a number of higher-level functions. However, the neural substrates of this behavioral phenotype are intricate and it is unknown through what precise biological mechanism variation in working memory is transmitted. In this review we explore different functional and structural components of the working memory circuitry, and the degree to which each of them is contributed to by genetic factors. Specifically, we consider dopaminergic function, glutamatergic function, white matter integrity and gray matter structure all of which provide potential mechanisms for the inheritance of working memory deficits. In addition to discussing the overall heritability of these measures we also address specific genes that may play a role. Each of these heritable components has the potential to uniquely contribute to the working memory deficits observed in genetic disorders, including 22q deletion syndrome, fragile X syndrome, phenylketonuria (PKU), and schizophrenia. By observing the individual contributions of disruptions in different components of the working memory circuitry to behavioral performance, we highlight the concept that there may be many routes to a working memory deficit; even though the same cognitive measure may be a valid endophenotype across different disorders, the underlying cause of, and treatment for, the deficit may differ. This has implications for our understanding of the transmission of working memory deficits in both healthy and disordered populations.
工作记忆是一种高度遗传的复杂认知特征，对许多高级功能至关重要。然而，这种行为表型的神经基础错综复杂，目前尚不清楚工作记忆的变化是通过什么精确的生物学机制传递的。在这篇综述中，我们探讨了工作记忆回路的不同功能和结构成分，以及遗传因素对它们各自的贡献程度。具体而言，我们考虑了多巴胺能功能、谷氨酸能功能、白质完整性和灰质结构，它们都为工作记忆缺陷的遗传提供了潜在的机制。除了讨论这些测量方法的整体遗传性外，我们还讨论了可能起作用的特定基因。这些可遗传的成分中的每一个都有可能独特地导致 22q 缺失综合征、脆性 X 综合征、苯丙酮尿症 (PKU) 和精神分裂症等遗传疾病中观察到的工作记忆缺陷。通过观察工作记忆回路不同成分的破坏对行为表现的个体贡献，我们强调了这样一种概念，即工作记忆缺陷可能有多种途径；即使相同的认知测量在不同的疾病中是有效的内表型，缺陷的潜在原因和治疗方法可能不同。这对我们理解健康和紊乱人群中工作记忆缺陷的传递具有重要意义。
