Molecular Neurophysiology and Biophysics Unit, NICHD, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892-4995, USA.
Mol Neurobiol. 2012 Jun;45(3):478-87. doi: 10.1007/s12035-012-8265-x. Epub 2012 Apr 22.
Discovering the etiology of pathophysiologies and aberrant behavior in many central nervous system (CNS) disorders has proven elusive because susceptibility to these diseases can be a product of multiple factors such as genetics, epigenetics, and environment. Advances in molecular biology and wide-scale genomics have shown that a large heterogeneity of genetic mutations are potentially responsible for the neuronal pathologies and dysfunctional behaviors seen in CNS disorders. Despite this seemingly complex array of genetic and physiological factors, many disorders of the CNS converge on common dysfunctions in memory. In this review, we propose that mechanisms underlying the development of many CNS disorders may share an underlying cause involving abnormal dendritic integration of synaptic signals. Through understanding the relationship between molecular genetics and dendritic computation, future research may uncover important links between neuronal physiology at the cellular level and higher-order circuit and network abnormalities observed in CNS disorders, and their subsequent affect on memory.
发现许多中枢神经系统(CNS)疾病的病理生理学和异常行为的病因一直难以捉摸,因为这些疾病的易感性可能是多种因素的产物,如遗传、表观遗传和环境。分子生物学的进步和大规模基因组学研究表明,大量的遗传突变可能是导致 CNS 疾病中神经元病理和功能障碍的原因。尽管存在这种看似复杂的遗传和生理因素的多样性,但许多 CNS 疾病都集中在记忆方面的共同功能障碍上。在这篇综述中,我们提出,许多 CNS 疾病的发展机制可能有一个共同的潜在原因,即突触信号的异常树突整合。通过了解分子遗传学和树突计算之间的关系,未来的研究可能会揭示细胞水平的神经元生理学与 CNS 疾病中观察到的高级回路和网络异常之间的重要联系,以及它们对记忆的后续影响。