Tully T
Cold Spring Harbor Laboratory, NY 11724, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13460-7. doi: 10.1073/pnas.93.24.13460.
The biological bases of learning and memory are being revealed today with a wide array of molecular approaches, most of which entail the analysis of dysfunction produced by gene disruptions. This perspective derives both from early "genetic dissections" of learning in mutant Drosophila by Seymour Benzer and colleagues and from earlier behavior-genetic analyses of learning and in Diptera by Jerry Hirsh and coworkers. Three quantitative-genetic insights derived from these latter studies serve as guiding principles for the former. First, interacting polygenes underlie complex traits. Consequently, learning/memory defects associated with single-gene mutants can be quantified accurately only in equilibrated, heterogeneous genetic backgrounds. Second, complex behavioral responses will be composed of genetically distinct functional components. Thus, genetic dissection of complex traits into specific biobehavioral properties is likely. Finally, disruptions of genes involved with learning/memory are likely to have pleiotropic effects. As a result, task-relevant sensorimotor responses required for normal learning must be assessed carefully to interpret performance in learning/memory experiments. In addition, more specific conclusions will be obtained from reverse-genetic experiments, in which gene disruptions are restricted in time and/or space.
如今，学习与记忆的生物学基础正通过一系列分子方法得以揭示，其中大多数方法都涉及对基因破坏所产生功能障碍的分析。这一观点既源于西摩·本泽及其同事早期对突变果蝇学习行为的“遗传剖析”，也源于杰里·赫什及其同事早期对双翅目昆虫学习行为的行为遗传学分析。后一类研究得出的三个数量遗传学见解为前一类研究提供了指导原则。首先，复杂性状由相互作用的多基因决定。因此，与单基因突变相关的学习/记忆缺陷只有在平衡的、异质的遗传背景中才能得到准确量化。其次，复杂的行为反应将由基因上不同的功能成分组成。因此，将复杂性状进行遗传剖析以得到特定的生物行为特性是有可能的。最后，与学习/记忆相关的基因破坏可能会产生多效性影响。因此，在解释学习/记忆实验中的表现时，必须仔细评估正常学习所需的与任务相关的感觉运动反应。此外，从反向遗传学实验中可以得出更具体的结论，在这类实验中，基因破坏在时间和/或空间上受到限制。
