The role of short-term synaptic plasticity in sensory processing and behavior

短期突触可塑性在感觉加工和行为中的作用

• 批准号: 9193874
• 负责人: Katherine Nagel
• 金额: $ 35.28万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9193874
• 关键词: Affect; Afferent Neurons; Animal Model; Back; Behavior; Behavioral; Behavioral Paradigm; Biological Models; Cells; Characteristics; Chemical Synapse; Code; Computer Simulation; Data; Defect; Development; Disease; Drosophila genus; Excitatory Synapse; Exhibits; Feedback; Flying body movement; Frequencies; Genetic; Goals; Inhibitory Synapse; Interneurons; Lead; Light; Lobe; Measures; Mental Depression; Mental disorders; Modeling; Molecular; Muscle; Neurons; Odors; Olfactory Pathways; Olfactory Receptor Neurons; Output; Presynaptic Receptors; Process; Property; Role; Sensory; Sensory Process; Shapes; Stimulus; Synapses; Synaptic Transmission; Synaptic plasticity; Testing; base; behavioral response; fly; genetic manipulation; insight; prevent; receptor; research study; response; sensory stimulus; synaptic depression; synaptic function; tool; transmission process

Chemical synapses exhibit various forms of short-term plasticity that determine what information they transmit to downstream circuits. Although the molecular mechanisms underlying this plasticity have been studied extensively, its consequences for circuit function and behavior are unclear. Here we propose to use the first olfactory relay of Drosophila as a model to understand the computational and behavioral consequences of short-term synaptic plasticity. Recently we found that each major synapse type in this circuit exhibits distinct forms of short-term plasticity. We developed a computational model that relates plasticity at these synapses to the ability of the circuit to encode fluctuating odor stimuli, such as the odor plumes a fly encounters in the natural world. In preliminary results, we have shown that we can use genetic manipulations to alter the dynamics of synaptic transmission at particular synapse types. In addition, we have developed a behavioral paradigm that allows us to measure behavioral responses to fluctuating odors with high temporal precision. We will leverage the powerful genetic tools available in Drosophila to manipulate short-term plasticity specifically at each synapse type in this circuit, and to measure the consequences of these manipulations for sensory encoding and behavior. We will compare the experimental effects of these manipulations to the predictions of our computational model. These experiments will allow us to quantitatively assess the contribution of synaptic processes to sensory coding and behavior, and will provide insight into the effects of synaptic perturbations in disease states.

化学突触表现出各种形式的短期可塑性，这些可塑性决定了它们传递什么信息 到下游电路。尽管这种可塑性的分子机制已经被研究过了， 广泛地说，它对电路功能和行为的影响尚不清楚。在这里，我们建议使用第一个 果蝇的嗅觉中继作为理解嗅觉的计算和行为后果的模型 短期突触可塑性最近我们发现，在这个回路中，每种主要的突触类型都表现出不同的 短期的可塑性。我们开发了一个计算模型，将这些突触的可塑性与 电路编码波动气味刺激的能力，例如苍蝇在空气中遇到的气味羽流。 自然界在初步结果中，我们已经表明，我们可以使用遗传操作来改变 特定突触类型的突触传递动力学。此外，我们还开发了一种行为 这一范例使我们能够以高时间精度测量对波动气味的行为反应。 我们将利用果蝇中强大的遗传工具来操纵短期可塑性 特别是在这个回路中的每种突触类型，并测量这些操作的后果， 感觉编码和行为。我们将比较这些操作的实验效果， 我们的计算模型的预测。这些实验将使我们能够定量评估 突触过程对感觉编码和行为的贡献，并将提供对 疾病状态中的突触扰动。