Biophysics of forward and lateral connections in a genetically-tractable circuit

遗传可控回路中前向和横向连接的生物物理学

• 批准号: 7544695
• 负责人: Hokto Kazama
• 金额: $ 4.96万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7544695
• 关键词: Address; Affect; Animals; Axon; Biological Models; Biophysics; Brain; Brain region; Cells; Characteristics; Chromosome Pairing; Data; Defect; Dendrites; Depth; Disease; Dorsal; Drosophila genus; Enhancers; Event; Figs - dietary; Genetic; In Vitro; Insecta; Interneurons; Intervention; Investigation; Label; Lateral; Lobe; Measures; Mental Depression; Molecular; Neurons; Neurosciences; Numbers; Odors; Olfactory Nerve; Olfactory Receptor Neurons; Physiology; Population; Probability; Problem Solving; Process; Property; Research; Role; Sensory; Sensory Process; Side; Site; Smell Perception; Staging; Stimulus; Synapses; Synaptic Transmission; System; Testing; Training; analog; in vivo; neural circuit; olfactory bulb; patch clamp; postsynaptic; presynaptic; prevent; receptor; response; sensory neuroscience; size; tool

DESCRIPTION (provided by applicant): Understanding how sensory representations are transformed in the brain is a fundamental problem in neuroscience. An important step in solving this problem is understanding the synaptic interactions within the neural circuit that carries out these transformations. Despite many studies of synaptic transmission in vitro, it remains unclear specifically which aspects of synaptic computation are critical in transforming natural sensory information encoded in spike trains in vivo. This project addresses this question in the Drosophila antennal lobe, where it is possible to characterize the physiology of synapses made between identified neurons whose responses to natural stimuli are well documented in vivo. The Drosophila antennal lobe, an analogue of the vertebrate olfactory bulb, consists of morphologically discrete modules called glomeruli, where axons of olfactory receptor neurons (ORNs) make synaptic contacts with the dendrites of projection neurons (PNs). Local interneurons (LNs) interconnect multiple glomeruli. Prior investigations have already characterized odor-evoked responses from both ORNs and PNs in vivo, and as a result the sensory transformations that occur in this brain region are beginning to be understood. This project examines the synaptic mechanisms underlying these sensory transformations. ORN-PN synaptic transmission will be characterized by recording from identified PNs while electrically stimulating the olfactory nerve. Interglomerular interactions among PNs and LNs will be characterized using genetically encoded "triggers" to selectively stimulate specific neurons in the brain while recording from other genetically-labeled neurons. Specific Aim #1 tests the hypothesis that the specific properties of ORN-PN synapses partially explain several key features of olfactory transformation in the antennal lobe. Specific Aim #2 tests the hypothesis that some characteristics of ORN-PN synaptic transmission are heterogeneous across glomeruli. Specific Aim #3 tests the hypothesis that PNs and LNs interact with each other across glomeruli. This study should substantially contribute to understanding sensory processing in the brain. Specifically, it should help us understand the role of specific synaptic properties in sensory computations. This in turn should inform the study of defects in synaptic transmission (synaptopathies) that affect specific sensory regions in the brain, and may ultimately be useful in the search for molecular interventions to remedy these defects. In addition, research into insect olfaction should help us understand and prevent the spread of insect-borne diseases.

描述（由申请人提供）：了解大脑中的感觉表征如何转变是神经科学的一个基本问题。解决这个问题的一个重要步骤是了解执行这些转换的神经回路内的突触相互作用。尽管对体外突触传递进行了许多研究，但目前尚不清楚突触计算的哪些方面对于转换体内尖峰序列中编码的自然感觉信息至关重要。该项目在果蝇触角叶中解决了这个问题，在那里可以描述已识别神经元之间形成的突触的生理学特征，这些神经元对自然刺激的反应在体内得到了很好的记录。果蝇触角叶是脊椎动物嗅球的类似物，由形态上离散的模块组成，称为肾小球，嗅觉受体神经元 (ORN) 的轴突与投射神经元 (PN) 的树突进行突触接触。局部中间神经元 (LN) 互连多个肾小球。先前的研究已经描述了体内 ORN 和 PN 的气味诱发反应，因此我们开始了解该大脑区域中发生的感觉转变。该项目研究了这些感觉转换背后的突触机制。 ORN-PN 突触传递的特征是在电刺激嗅觉神经的同时记录已识别的 PN。 PN 和 LN 之间的肾小球间相互作用将使用基因编码的“触发器”来表征，以选择性地刺激大脑中的特定神经元，同时记录其他基因标记的神经元。具体目标#1 测试了这样一个假设：ORN-PN 突触的特定属性部分解释了触角叶嗅觉转换的几个关键特征。具体目标 #2 测试以下假设：ORN-PN 突触传递的某些特征在肾小球之间是异质的。具体目标#3 检验 PN 和 LN 跨肾小球相互作用的假设。这项研究应该大大有助于理解大脑的感觉处理。具体来说，它应该帮助我们理解特定突触特性在感觉计算中的作用。这反过来应该为影响大脑特定感觉区域的突触传递缺陷（突触病）的研究提供信息，并最终可能有助于寻找分子干预措施来弥补这些缺陷。此外，对昆虫嗅觉的研究应该有助于我们了解和预防虫媒疾病的传播。