Synaptic Processes Mediating Cortical Odor Coding

项目概要（见说明）：摘要嗅觉信息是由嗅球小球的组合编码的，它们分别代表不同气味的不同化学特征。这些信息被传递到梨状皮质，在那里它驱动神经元的激活，这些神经元的协同活动被认为导致整体的气味感知。梨状神经元也通过丰富的循环回路相互连接。在这里，我们建议扩展我们以前的工作解剖的细胞机制，塑造这些corticalensembles。我们对浓度不变性问题特别感兴趣。气味剂受体特异性取决于配体浓度，在更高的气味剂浓度下激活更多的受体。然而，气味在很大的浓度范围内保持它们的特性，这要求气味表示相对于沿着嗅觉通路的沿着某处的浓度被归一化。这种正常化发生在整个大脑的神经回路中，尽管这种正常化背后的细胞机制仍然知之甚少。最近的实验表明，梨状皮质中的气味诱发活动是相对浓度不变的，与气味感受器的相对浓度不变的性质相一致。在指导阶段的这个奖项，我们检查了经常性的梨状神经网络在体外，并发现了这个电路的功能，准备在塑造气味诱发的皮层活动中发挥重要作用，并提出了一个电路级的解决方案，以影响浓度不变性。在这里，我们将定量表征的气味表示从嗅球梨状皮质的转化，在体内使用双光子显微镜图像气味诱发的活动在人群中的嗅球僧帽细胞和主要神经元梨状皮质（目标1）。我们将建立一个实验约束的网络级计算模型，以测试我们的电路级模型是否足以影响浓度不变性（目标2）。最后，我们将使用遗传和病毒策略来选择性地消除循环回路，以直接测试这些回路在介导浓度不变性中的作用（目标3）。这项研究计划采用了丰富的概念和技术方法，

PROJECT SUMMARY (See instructions); Abstract Olfactory information is encoded by combinations of olfactory bulb glomeruli, which individually represent distinct chemical features of different odorants. This information is transmitted to the piriform cortex, where it drives activation of ensembles of neurons whose concerted activity is thought to lead to a holistic odor percept. Piriform neurons are also interconnected by a rich recurrent circuitry. Here, we propose to extend our previous work dissecting the cellular mechanisms that shape these corticalensembles. We are particularly interested in the problem of concentration invariance. Odorant receptor specificity depends on ligand concentration, with more receptors being activated at higher odorant concentrations. However, odors retain their identity over a large range of concentrations, requiring that odor representations be normalized with respect to concentration somewhere along the olfactory pathway. Such normalization occurs in neural circuits throughout the brain, although the cellular mechanisms underlying this normalization remain poorly understood. Recent experiments suggest odor-evoked activity in piriform cortex is relatively concentration invariant, consistent with the relatively concentration-invariant quality of the odor percept. In the mentored phase of this award we examined the recurrent piriform network in vitro and discovered features of this circuit that are poised to play a major role in shaping odor-evoked cortical activity and suggest a circuit-level solution to effecting concentration invariance. Here, we will quantitatively characterize the transformation of odor representations from olfactory bulb to piriform cortex using in vivo two-photon microscopy to image odor-evoked activity in populations of olfactory bulb mitral cells and principal neurons in piriform cortex (Aim 1). We will build an experimentally constrained, network-level computational model to test the sufficiency of our circuit-level model for effecting concentration invariance (Aim 2). Finally, we will use genetic and viral strategies to selectively eliminate the recurrent circuitry to directly test the role of these circuits in mediating concentration invariance (Aim 3). This research program employs a rich arsenal of conceptual and technical approaches that have