CRCNS: Odor processing by cortical neural circuits

项目摘要 神经细胞类型的巨大多样性是大脑的一个决定性特征。不同 神经回路由无数不同的细胞类型组成，每种细胞都有特定的固有属性 以及突触连接的模式，它们将神经输入转换并将信息传递给 下游目标。然而，尽管它们在神经处理中具有基本的重要性，我们的 了解不同类型的细胞对神经回路功能的不同贡献 计算仍然很差。在这里，调查人员利用了一种高度易处理的神经回路，即 小鼠嗅觉(梨状，PCX)皮质，以确定气味刺激的信息是如何编码的， 转化，并输送到其不同的下游目标区。这项提议的目的是 是将在PCX神经元中观察到的不同气味反应记录到已识别的神经细胞类型上， 由它们的形态、内在属性和连通性来定义。这将通过一个 协作、多学科、迭代计算-实验方法，涉及 计算建模、体内双光子成像、体外电生理学、行为学、 化学遗传学和解码分析。研究人员的工作假设是不同的 气味的特征--其特性、强度和价态--被有选择地提取和编码 通过PCX神经元的不同子集，通过其不同的内在和局部电路 属性，然后有选择地传输到不同的目标区域。 在提出的两个目标中，研究人员将成像不同气味引起的活动 清醒、行为正常的小鼠PCX神经元亚群中的多种浓度。他们会比较 他们在计算模型中模拟气味诱发活动的成像数据，在该模型中 结合了这些神经元局部突触连接的特定固有属性和模式 PCX神经元亚群。在Aim1中，研究人员将对气味反应进行成像和建模 两种形态截然不同的主要神经元亚型：半月形细胞和浅表型 锥体细胞。在目标2中，他们使用了类似的方法，但使用了PCX神经元亚群 由其特定的投射目标定义。老鼠将会发出一种去/不去的气味 成像过程中的辨别任务，允许表征对不同气味的反应 同一性、浓度或价态。这种实验-计算方法将决定 在多大程度上不同的固有属性和特定的连接模式 细胞类型解释了它们对气味反应的不同。至关重要的是，模型之间的不匹配 实验结果将揭示这些单元和电路的其他属性，这些属性可能 确定他们的气味反应，这可以并将进行实验测试。实现以下目标： 因此，这一建议将提供一个连贯的框架，以了解不同的功能 可以选择性地提取、编码气味刺激并将其传送到适当的下游 目标。

Project Summary The enormous diversity of neural cell types is a defining characteristic of the brain. Different neural circuits consist of a myriad of distinct cell types, each with specific intrinsic properties and patterns of synaptic connectivity, which transform neural input and convey this information to downstream targets. However, despite their fundamental importance in neural processing, our understanding of how individual cell types differentially contribute to neural circuit function and computation remains poor. Here, the investigators leverage a highly tractable neural circuit, the mouse olfactory (piriform, PCx) cortex, to determine how information about odor stimuli is encoded, transformed, and conveyed to its different downstream target areas. The objective of this proposal is to register diverse odor responses observed in PCx neurons onto identified neural cell types, defined by their morphology, intrinsic properties, and connectivity. This will be achieved via a collaborative, multidisciplinary, iterative computational-experimental approach, involving computational modeling, in vivo two­ photon imaging, in vitro electrophysiology, behavior, chemogenetics and decoding analyses. The investigators' working hypothesis is that different features of an odor - its identity, intensity, and valence - are selectively extracted and encoded by distinct subsets of PCx neurons by virtue of their different intrinsic and local circuit properties, and then selectively transmitted to different target areas. In the two aims proposed, the investigators will image activity evoked by different odorants at multiple concentrations in subpopulations of PCx neurons in awake, behaving mice. They will compare their imaging data with simulated odor-evoked activity in a computational model in which they incorporate the specific intrinsic properties and patterns of local synaptic connectivity of these subpopulations of PCx neurons. In Aim1, the investigators will image and model odor responses in two morphologically distinct subtypes of principal neurons, semilunar cells and superficial pyramidal cells. In Aim 2 they use a similar approach, but with subpopulations of PCx neurons defined by their specific projection targets. Mice will be performing a go/no go odor discrimination task during imaging, allowing characterization of responses to odors with different identities, concentrations or valence. This experimental-computational approach will determine the extent to which the distinct intrinsic properties and specific connectivity patterns of different cell-types accounts for differences in their odor responses. Crucially, mismatches between modeling and experimental results will reveal additional properties of these cells and circuitry that may determine their odor responses, which can and will be tested experimentally. Achieving the goals of this proposal will therefore provide a coherent framework for understanding how different features of an odor stimulus can be selectively extracted, encoded and conveyed to appropriate downstream targets.