Synaptic Processes Mediating Cortical Odor Coding

项目总结（见说明书）；嗅觉信息是由嗅球肾小球的组合编码的，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群的激活，这些神经元的协同活动被认为导致了整体的气味感知。梨状神经元也通过丰富的循环电路相互连接。在这里，我们建议扩展我们之前的工作，剖析形成这些皮质整体的细胞机制。我们对集中不变性问题特别感兴趣。气味受体的特异性取决于配体的浓度，在更高的气味浓度下，更多的受体被激活。然而，气味在很大的浓度范围内保持其特性，这就要求气味表征在嗅觉通路的某个地方对浓度进行标准化。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，梨状皮质的气味诱发活动是相对浓度不变的，这与气味感知的相对浓度不变的质量一致。在本奖项的指导阶段，我们在体外研究了反复发作的梨状网络，并发现了该回路的特征，这些特征在形成气味诱发的皮层活动中起着重要作用，并提出了影响浓度不变性的回路级解决方案。在这里，我们将定量表征气味表征从嗅球到梨状皮质的转化，使用体内双光子显微镜来成像嗅球二尖瓣细胞和梨状皮质主要神经元群体的气味诱发活动（Aim 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对影响浓度不变性的充分性（目标2）。最后，我们将使用遗传和病毒策略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（目的3）。这个研究项目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