Mutational Analyses of Learning and Memory

我们的目标是利用现代突变分子遗传学的力量和特异性来揭示学习和记忆的组成过程。突变体分析有两种途径：候选基因靶向（反向遗传学）和筛选（正向遗传学）方法。候选靶向方法包括识别在学习或记忆中起重要作用的特定基因，然后测试这些基因的靶向突变（自然发生的或实验者诱导的）在各种学习模式中的效果。特别是，首先，我们将在我们几年前分离的lrn-1和lrn-2突变蠕虫中找到确切的突变基因。为了做到这一点，我们将利用一种学习和记忆的测定法，该测定法采用了对病原菌的学习性回避。对这些基因的特异性识别将使我们能够揭示这些基因通常在哪里表达，以及它们在哪些神经元中起作用以允许学习发生。第二，我们建议筛选新的遗传突变体，在我们最有效的学习试验中，采用蠕虫避免苯甲醛的气味时，这种气味预示着没有食物。这些新的突变体将使学习和记忆过程的结构成分得以揭示。

Our goal is to use the power and specificity of modern mutational molecular genetics to reveal the component processes of learning and memory. There are two routes to mutant analysis: candidate gene targeting (reverse genetics) and screening (forward genetics) approaches. The candidate targeting approach involves identifying specific genes that are candidates for important roles in learning or memory, and then testing the effects of targeted mutations of these genes (naturally occurring or experimenter induced) in various learning paradigms.In particular, first, we will find the exact gene mutated in the lrn-1 and lrn-2 mutant worms that we isolated several years ago. To do this, we will take advantage of an assay of learning and memory employing the learned avoidance of pathogenic bacteria. The specific identification of these genes will enable us to reveal where the genes normally are expressed and in which neurons they function to allow learning to take place. Second, we propose to screen for novel genetic mutants that have deficits in learning in our most potent learning assay that employs the worms avoidance of the smell of benzaldehyde when that smell predicts the absence of food. These new mutants will allow the structural components of the learning and memory processes to be revealed.