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

嗅球是嗅觉信息在大脑中的第一个处理站。这个皮层下区域将信息发送到几个嗅觉皮层中心，并接收直接的反向投射，形成广泛的皮层-皮层下回路。到目前为止，这些回路的精确生理功能还没有得到很好的描述。一个突出的理论来自计算模型表明，嗅觉皮质-皮质下回路中继气味诱发的神经元活动回OB，从而提高检测的“前景”的气味在嘈杂的背景。这种“图形-背景分离”对于许多感觉处理方式是必不可少的。在Rothermel和施瓦茨实验室之间的串联提议中，我们将研究OB和ist相关皮层中心之间的相互神经元活动的关系，以揭示它们对图形-背景分离的贡献。具体来说，我们将功能比较OB和前嗅核（AON），以及OB和前梨状皮质（APC）之间形成的皮质回路。为此，我们将采用双色2 PCa 2+成像的皮层纤维和OB输出神经元同时（目的1），探讨其在不同的嗅觉任务的时空关系。这些实验的数据将被用来完善现有的OB-嗅觉皮层模型的数字背景分离（目标2）。在目标3中，我们将建立嗅觉皮层的活动依赖性标记方法。活性AON和APC神经元的气味依赖性标记将允许使用光片荧光放大显微镜（LSFEM）以前所未有的细节深入了解它们的差异连接/投射组成。最后，光遗传致动器在活性标记神经元中的表达将使我们能够探索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-皮层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.