Electrophysiological Analysis of Olfactory Representations in Drosophila

果蝇嗅觉表征的电生理分析

• 批准号: 8888697
• 负责人: Dinu Florentin ALBEANU
• 金额: $ 44.34万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8888697
• 关键词: Animal Model; Animals; Area; Arousal; Behavioral; Biological Models; Biological Neural Networks; Brain; Calcium; Categories; Cells; Code; Coupling; Disease; Dopamine; Drosophila genus; Electrophysiology (science); Environment; Genes; Genetic; Image; Invertebrates; Label; Learning; Lobe; Maps; Mediating; Memory; Monitor; Motor; Motor Neurons; Motor output; Mushroom Bodies; Neuromodulator; Neurons; Odors; Olfactory Pathways; Output; Parkinson Disease; Pattern; Perception; Plastics; Play; Population; Process; Property; Retrieval; Role; Satiation; Sensory; Sensory Process; Shapes; Side; Signal Transduction; Site; Staging; Stimulus; Synapses; System; Testing; Work; base; behavioral response; experience; flexibility; fly; insight; neuroregulation; optogenetics; public health relevance; response; sensory input; tool; transmission process

 DESCRIPTION (provided by applicant): All sensory circuits, including the olfactory system, ascend from the sensory periphery to higher brain areas where stimuli are represented in sparse, stimulus-specific activity patterns. This sparse format is useful for accurate memory formation and retrieval. However, these specific signals must converge at some downstream site, given the limited numbers of motor neurons that represent the ultimate output of the circuit. We know very little about sensory processing downstream of sparse representations, on the converging side of neural networks. The Drosophila mushroom body (MB) has been an important model system for studying sparse representations in the olfactory system. New genetic labeling tools have revealed that the 2000 Kenyon cells (KCs) of the MB converge down onto a total of only 35 MB Output Neurons (MBONs). We will use these new tools to target MBONs for both electrophysiological recordings and calcium imaging, to examine nearly the entire layer of the network where the transition from sensory to motor begins. Using imaging to get a population-level view of activity patterns, we will determine how odor representations are reformatted as the circuit transitions from KCs to MBONs. Many of the MBONs are uniquely identifiable using these genetic labels. This enables us to compare their response properties of the same neuron across flies that have had different types of olfactory experience, to examine how plasticity shapes odor representations at this layer. Additionally, the neuromodulator dopamine is thought to play an important role in signal transmission across the KC-MBON synapse. By optogenetically controlling these specific dopaminergic inputs, we can examine how this neuromodulator regulates the flow of olfactory information across this layer of the circuit. Insights from this work will provide an important conceptual framework to understand how sensory perception is turned into action, and potentially contribute to our understanding of how sensory-motor coupling is impaired in disease states such as Parkinson's.

 描述（由申请人提供）：所有感觉回路，包括嗅觉系统，从感觉外围上升到较高的大脑区域，其中刺激以稀疏的、刺激特异性的活动模式表示。这种稀疏格式对于准确的记忆形成和检索很有用。然而，考虑到代表电路最终输出的运动神经元数量有限，这些特定信号必须在下游某个位点汇聚。 我们对神经网络收敛端稀疏表示下游的感觉处理知之甚少。果蝇蘑菇体（MB）一直是研究嗅觉系统稀疏表征的重要模型系统。新的基因标记工具显示，MB 的 2000 个 Kenyon 细胞 (KC) 汇聚成总共只有 35 个 MB 输出神经元 (MBON)。我们将使用这些新工具针对 MBON 进行电生理记录和钙成像，以检查从感觉到运动转变开始的几乎整个网络层。使用成像来获取群体水平的活动模式视图，我们将确定当电路从 KC 转换到 MBON 时如何重新格式化气味表示。许多 MBON 可以使用这些基因标签进行唯一识别。这使我们能够比较具有不同类型嗅觉体验的果蝇相同神经元的反应特性，以检查可塑性如何塑造这一层的气味表征。此外，神经调节剂多巴胺被认为在 KC-MBON 突触信号传输中发挥着重要作用。通过光遗传学控制这些特定的多巴胺能输入，我们可以检查这种神经调节剂如何调节嗅觉信息在这一层电路中的流动。这项工作的见解将为理解感官知觉如何转化为行动提供一个重要的概念框架，并可能有助于我们理解帕金森氏症等疾病状态下感觉-运动耦合如何受损。