Olfactory memory trace formation in Drosophila

描述(申请人提供)：这项研究项目的目标是定义大脑在其组成神经元中组织不同类型记忆的逻辑。该项目对比了大脑如何组织与奖励线索相关的嗅觉记忆和与厌恶线索相关的嗅觉记忆，并深入探讨了一些潜在的机制。这项研究项目使用了黑腹果蝇模型系统，因为利用嗅觉线索调节果蝇很容易，而且能够窥视活着动物的大脑，观察不同组神经元的活动。后一种方法，功能光学细胞成像，利用携带表达钙内流、突触传递或其他神经元事件的转基因报告的苍蝇，来监测表达神经元在条件化前后的神经元反应特性的变化。到目前为止，已经使用厌恶嗅觉条件反射定义了六种不同的细胞记忆痕迹。这些痕迹在嗅觉神经系统的不同神经元中形成，并以不同的时间动力学发生。在一次有益的嗅觉条件作用事件之后，这些神经元中出现的记忆痕迹将与记忆痕迹形成的分子机制一起被研究。由于几乎每一种神经精神障碍都会影响记忆的形成，这些研究将有助于理解正常大脑和疾病大脑中的记忆形成。 公共卫生相关性：大多数人类神经和精神疾病涉及学习和记忆障碍。这个项目将研究大脑如何编码不同类型记忆的逻辑，将与奖赏线索相关的记忆与与厌恶线索相关的记忆进行对比，并详细说明潜在的分子机制。我们将利用黑腹果蝇模型--因为研究这种有机体的记忆形成很容易，而且能够窥探它的大脑，观察学习过程中神经元的活动--来获得有助于理解大脑，包括人类大脑，如何组织不同类型的记忆，以及大脑紊乱如何扰乱学习和记忆的知识。

DESCRIPTION (provided by applicant): The goal of this research project is to define the logic by which the brain organizes different types of memories among its component neurons. The project contrasts how the brain organizes olfactory memories learned in association with a rewarding cue and those learned in association with an aversive cue, and delves into some of the underlying mechanisms. The research project utilizes the model system Drosophila melanogaster because of the ease in conditioning the fly using olfactory cues and because of the ability to peer into the brain of living animals and watch the activity of different sets of neurons. The latter approach, functional optical cellular imaging, employs flies carrying transgenes expressing reporters for calcium influx, synaptic transmission, or other neuronal events, to monitor changes in neuronal response properties among the expressing neurons before and after conditioning. To date, six different cellular memory traces have been defined using aversive olfactory conditioning. These traces form in different sets of neurons in the olfactory nervous system and occur with differing temporal dynamics. The memory traces that occur within these same neurons after a rewarding olfactory conditioning event will be examined along with the molecular mechanisms underlying memory trace formation. Since nearly every neuropsychiatric disorder affects memory formation, these studies will aid in understanding memory formation in the normal brain as well as in the diseased brain. PUBLIC HEALTH RELEVANCE: The majority of human neurological and psychiatric disorders involve impairment in learning and memory. This project will examine the logic of how the brain encodes different types of memories, contrasting memories associated with rewarding cues versus memories associated with aversive cues, along with detailing the underlying molecular mechanisms. We will utilize the model Drosophila melanogaster - because of the ease of studying memory formation in this organism and the ability to peer into its brain and watch the activity of neurons during learning - to obtain knowledge that will contribute to understanding how the brain, including the human brain, organizes different types of memories and how brain disorders disrupt learning and memory.