Investigating the molecular and neuronal basis of olfactory plasticity in C. elegans.

 描述(由申请人提供)：有机体探测和响应环境刺激的能力对其生存至关重要。对于动物来说，为了调整行为反应和最大限度地适应环境，纳入背景信息(如内部状态或外部线索)尤其重要。这种行为可塑性在很大程度上是在学习或适应的背景下进行的研究。然而，环境线索如何调节对幼稚刺激的先天反应的价态仍然知之甚少。行为可塑性可能源于神经功能的遗传、分子和电路水平的变化，最终导致有机体在动态环境中茁壮成长的能力。本论文的总体目标是研究线虫嗅觉可塑性的分子和神经机制。我初步发现，虽然在稀疏培养条件下生长的线虫避免了高浓度的挥发性化学物质1-己醇，但在高种群密度下生长的动物反而强烈地被这种气味所吸引。我的结果表明，嗅觉反应的这种可塑性是由信息素介导的，信息素可能是种群密度的线索。我将利用线虫的实验适应性来确定对1-己醇的反应背后的基因、神经元和电路，并研究这些反应是如何被上下文线索和经验改变的。为此，我将利用一种新的量化方法和高分辨率的数据分析算法。这项研究的洞察力将阐明与感觉可塑性有关的保守的分子和神经元通路。许多神经疾病--从自闭症等发育障碍到阿尔茨海默氏症和帕金森氏症等神经退行性疾病--都源于神经可塑性的潜在缺陷。因此，除了在健康的背景下理解可塑性的机制外，这项工作对于理解疾病状态的潜在机制也具有重要的意义。

 DESCRIPTION (provided by applicant): An organism's ability to detect and respond to environmental stimuli is critical for its survival. It is particularly important for animals to incorporate contextual information, such as internal state or external cues, in order to modify behavioral responses and maximize fitness. This behavioral plasticity has largely been studied in the context of learning or adaptation. However, how environmental cues modulate the valence of innate responses to naïve stimuli remains poorly understood. Behavioral plasticity can stem from genetic, molecular, and circuit level changes in neural function, ultimately leading to an organism's ability to thrive in a dynamic environment. The overall goal of my thesis is to investigate the molecular and neuronal mechanisms underlying olfactory plasticity in C. elegans. Preliminarily, I have found that while C. elegans grown under sparse culture conditions avoid high concentrations of the volatile chemical 1-hexanol, animals grown at high population density are instead robustly attracted to this odorant. My results indicate that this plasticity in olfactoy responses is mediated by pheromones, which may serve as a population density cue. I will exploit the experimental amenability of C. elegans to identify the genes, neurons and circuits that underlie the responses to 1-hexanol, and investigate how these responses are modified by contextual cues and experience. To do so, I will utilize a novel quantitative approach and high-resolution data analysis algorithms. Insights from this research will shed light on conserved molecular and neuronal pathways involved in sensory plasticity. Many neurological disorders-from developmental disorders such as autism to neurodegenerative diseases such as Alzheimer's and Parkinson's-stem from underlying deficits in neuroplasticity. Therefore, in addition to understanding the mechanisms of plasticity in a healthy context, this work has important implications for understanding the mechanisms underlying disease states.