Electrophysiological Analysis of Olfactory Representations in Drosophila

 描述(申请人提供)：所有感觉回路，包括嗅觉系统，从感觉外围上升到更高的大脑区域，在那里刺激以稀疏的、刺激特定的活动模式表示。这种稀疏格式对于准确的记忆形成和检索非常有用。然而，鉴于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某个下游位置会聚。 在神经网络的收敛端，我们对稀疏表示的下游感觉处理知之甚少。果蝇蘑菇体是研究嗅觉系统稀疏表征的重要模型系统。新的遗传标记工具显示，MB的2000个Kenyon细胞(KCs)汇聚到总共只有35MB的输出神经元(MBON)上。我们将使用这些新工具来针对MBON进行电生理记录和钙成像，以检查从感觉到运动开始转换的网络的几乎整个层。使用成像来获得活动模式的总体级别的视图，我们将确定当电路从KCs过渡到MBON时，气味表示如何重新格式化。许多MBON可以使用这些遗传标签进行唯一识别。这使我们能够比较不同类型嗅觉体验的苍蝇对同一神经元的反应特性，以检查可塑性如何塑造这一层的气味表示。此外，神经调节剂多巴胺被认为在KC-MBON突触的信号传递中发挥重要作用。通过光基因控制这些特定的多巴胺能输入，我们可以研究这种神经调节剂如何调节通过这一层电路的嗅觉信息流。这项工作的见解将为理解感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在帕金森氏症等疾病状态下感觉-运动耦合是如何受损的。

 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.