Role of cortico-subcortical loops in olfactory stimulus detection and figure background separation

嗅球（OB）是大脑中嗅觉感觉信息的第一个处理站。这个皮层下区域向几个嗅觉皮层中心发送信息，并接受直接的反向投射，形成广泛的皮层-皮层下回路。到目前为止，这些回路的确切生理功能还没有得到很好的描述。一个来自计算模型的重要理论表明，嗅觉皮质-皮质下环将气味诱发的神经元活动传递回OB，从而增强了在嘈杂背景下对“前景”气味的检测。这种“图像-背景分离”对于许多感觉处理方式是必不可少的。在Rothermel和Schwarz实验室的联合提议中，我们将研究OB和ist相关皮层中心之间的互反神经元活动关系，以揭示它们对图像-背景分离的贡献。具体来说，我们将在功能上比较OB和前嗅核（AON）以及OB和前梨状皮质（APC）之间形成的皮质环。为此，我们将同时使用皮质纤维和OB输出神经元的双色2P Ca2+成像（目的1）来研究它们在不同嗅觉任务中的时空关系。这些实验的数据将用于改进现有的ob -嗅皮质图像背景分离模型（目的2）。在目标3中，我们将为嗅觉皮层建立一种活动依赖的标记方法。对活性AON和APC神经元的气味依赖性标记将使我们能够利用荧光扩展显微镜（LSFEM）以前所未有的细节了解它们的不同连接组/投射组组成。最后，光致动器在活动标记神经元中的表达将使我们能够探讨AON/APC活性在气味检测和图像背景分离中的因果关系（目的4）。这个项目的成功完成将从根本上增加我们对ob -皮质回路对嗅觉处理和气味引导行为的生理意义的理解。

The olfactory bulb (OB) is the first processing station of olfactory sensory information in the brain. This subcortical area sends information to several olfactory cortical centers and receives direct back projections forming extensive cortico-subcortical loops. So far, the precise physiological function of these loops is poorly described. A prominent theory derived from computational modeling suggests that olfactory cortico-subcortical loops relay odor-evoked neuronal activity back to the OB, thereby enhancing the detection of "foreground" odors in noisy backgrounds. This ‘Figure-background separation’ is essential for many sensory processing modalities. In this tandem proposal between the Rothermel and Schwarz labs, we will study the relation of reciprocal neuronal activity between OB and ist associated cortical centers to uncover their contribution to figure-background separation. Specifically, we will functionally compare the cortical loops formed between OB and anterior olfactory nucleus (AON), as well as OB and anterior piriform cortex (APC). To this end, we will employ dual-color 2P Ca2+ imaging of cortical fibers and OB output neurons simultaneously (Objective 1) to investigate their spatio-temporal relation in different olfactory tasks. Data from these experiments will be used to refine existing OB-olfactory cortex models of figure background separation (Objective 2). In Objective 3 we will then establish an activity-dependent labeling approach for the olfactory cortex. Odor-dependent labeling of active AON and APC neurons will allow insights into their differential connectomic/projectomic composition in unprecedented detail using light sheet fluorescence expansion microscopy (LSFEM). Finally, the expression of optogenetic actuators in activity-tagged neurons will allow us to probe into the causal relationship of AON/APC activity in odor detection and figure background separation (Objective 4). Successful completion of this project will fundamentally increase our understanding of the physiological implications of OB-cortical loops for olfactory processing and odor-guided behaviors.