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

嗅球(OB)是大脑中第一个处理嗅觉信息的站点。这个皮质下区域将信息发送到几个嗅觉皮质中心，并接受直接的背部投射，形成广泛的皮质-皮质下环路。到目前为止，这些环的确切生理功能还没有得到很好的描述。一项来自计算模型的重要理论表明，嗅觉皮质-皮质下环路将气味诱发的神经元活动传递回OB，从而增强了对嘈杂背景中“前景”气味的检测。这种“图形-背景分离”对于许多感觉处理方式来说是必不可少的。在Rothermel和Schwarz实验室的这个串联方案中，我们将研究OB和IST相关皮质中心之间的相互神经元活动关系，以揭示它们对图形-背景分离的贡献。具体地说，我们将从功能上比较OB和前嗅核(AON)以及OB和梨状皮质(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钙成像(目标1)来研究它们在不同嗅觉任务中的时空关系。这些实验的数据将被用来改进现有的体形背景分离的OB-嗅觉皮质模型(目标2)。在目标3中，我们将为嗅皮层建立一种依赖活动的标记方法。对活性AON和APC神经元的气味依赖标记将使人们能够使用光片荧光扩展显微镜(LSFEM)以前所未有的细节深入了解它们的不同连接/投射成分。最后，光发生致动器在活性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形背景分离中的因果关系(目标4)。这个项目的成功完成将从根本上增加我们对OB-大脑皮层环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.