Electrophysiological Analysis of Olfactory Representations in Drosophila

 描述（由申请人提供）：所有感觉回路，包括嗅觉系统，从感觉外周上升到更高的大脑区域，其中刺激以稀疏的刺激特异性活动模式表示。这种稀疏的格式对于准确的记忆形成和提取是有用的。然而，这些特定的信号必须在某个下游站点收敛，因为代表回路最终输出的运动神经元数量有限。 我们对稀疏表示下游的感觉处理知之甚少，在神经网络的收敛方面。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（KC）收敛到总共只有35个MB输出神经元（MBON）。我们将使用这些新工具来靶向MBON进行电生理记录和钙成像，以检查从感觉到运动的过渡开始的几乎整个网络层。使用成像得到一个人口水平的活动模式的看法，我们将确定如何气味表征重新格式化的电路从KC到MBON的过渡。许多MBON使用这些遗传标记是唯一可识别的。这使我们能够比较具有不同类型嗅觉体验的果蝇的相同神经元的反应特性，以研究可塑性如何在这一层塑造气味表征。此外，神经调质多巴胺被认为在跨KC-MBON突触的信号传递中起重要作用。通过光遗传学控制这些特定的多巴胺能输入，我们可以研究这种神经调节剂如何调节嗅觉信息在这一层回路中的流动。这项工作的见解将提供一个重要的概念框架，以了解感官知觉如何转化为行动，并可能有助于我们了解在帕金森氏症等疾病状态下感觉-运动耦合如何受损。

 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.