Mechanisms of short term habituation in C. elegans

虽然许多研究者关注长期记忆的机制，但关注短期记忆机制的研究者较少。本提案中所描述的研究目标是专注于发现一种非常简单的学习形式的短期记忆的机制，在一个非常简单的模型系统中，线虫的习惯化。习惯化包括学习忽略重复的、没有任何意义的刺激（比如交通的声音、房间里风扇的声音、树上树叶的移动）。所有的动物都能学会这个。我们将在行为水平，神经回路水平和基因水平上研究这种学习的机制。对于拟议研究的行为方面，我们将尝试将行为分解为其组成部分，以调查除了刺激间隔（刺激频率）之外，习惯化的反应幅度和反应频率的哪些特征是独立介导的。在神经元水平上，我们将使用工具来评估已识别神经元(即。绿色荧光蛋白，Western blots，定量实时PCR，转基因细胞特异性突变拯救)，重点关注介导习惯化不同方面的机制是在感觉神经元还是中间神经元。最后，在基因水平上，我们将使用遗传筛选来鉴定在秀丽隐杆线虫的习惯化中起作用的大量基因。此外，我们将分析我们识别的突变体中的经典条件反射，看看影响习惯化的基因是否也影响经典条件反射。通过这种方式，我们将研究习惯化和经典条件作用之间的关系。

Although many researchers focus on the mechanisms of long-term memory, there are fewer researchers who focus on the mechanisms of short-term memory. The objectives of the research described in this proposal are to focus on discovering the mechanisms underlying short-term memory for a very simple form of learning, habituation in a very simple model system, the nematode C. elegans. Habituation involves learning to ignore stimuli that are repeated and that do not have any meaning (i.e. traffic sounds, the sound of a fan in the room, the movement of leaves on a tree). All animals can learn this. We will approach studying the mechanism of this type of learning at the level of behaviour, at the level of the neural circuit and at the level of genes. For the behavioural aspects of the proposed research we will try to break the behaviour down into its component parts in order to investigate which features in addition to interstimulu interval (stimulus frequency), response magnitude and response frequency of habituation are independently mediated. At the level of the neurons we will use tools to assess gene activation in identified neurons (ie. green fluorescent protein, Western blots, quantitative real time PCR, transgenic cell specific rescues of mutations) to focus on whether the mechanisms mediating different aspects of habituation are in the sensory neurons or the interneurons in origin. Finally at the level of the gene we will use a genetic screen to identify a large number of genes that play a role in habituation in C. elegans. In addition we will analyze classical conditioning in the mutants we identify to see whether genes that affect habituation also affect classical conditioning. In this way we will investigate the relationship between habituation and classical conditioning.