Modulation of recurrent processing within olfactory bulb glomerular columns via granule cells, including their centrifugal glutamatergic inputs from PC and AON

嗅球颗粒细胞(GCs)通过相互突触形成的短距离经常性联系，在调节球主要神经元--二尖瓣细胞和簇状细胞(MTCs)的气味诱发活动中发挥重要作用，并被远程离心力输入大量靶向。先前的工作表明，GC在OB的很大一部分与MTC相连，GC介导的抑制是塑造OB活动的关键因素。此外，GC互易脊椎的工作原理已被阐明到一定程度，从而可以建立关于这一最紧凑的递归微电路功能的假设。然而，在我们对GCs在嗅觉处理中的作用的理解上-在单个突触的水平和球部网络功能之间-仍然有很大的差距。这个项目的总体目标是描绘OB中GC介导的抑制逻辑，即GC上突触的功能组织，允许使用逆行病毒标记、大规模电子显微镜和同步辐射X射线断层扫描，对激活的肾小球如何相互作用以及如何与不同群体的离心性输入进行解剖学预测。这一详细的解剖学分析将产生输入分布模式，然后将其用于通过多部位3D去势刺激GC。这一办法将使我们能够解决地方经常性投入和离心性投入如何协调行动以调整组织预算办公室的信息处理的问题。

Granule cells (GCs) of the olfactory bulb (OB) play a major role in modulating the odour-evoked activity of bulbar principal neurons, the mitral and tufted cells (MTCs), via short-range recurrent connections formed by reciprocal synapses, and are massively targeted by long-range centrifugal inputs. Previous work has shown that GCs are connected to MTCs across large portions of the OB and that GC-mediated inhibition is a key player in shaping OB activity. Also, the operational principles of GC reciprocal spines have been elucidated to a degree that allows building hypotheses on the function of this most compact recurrent microcircuit. However, there is still a substantial gap in our understanding of the role of GCs in olfactory processing - between the level of individual synapses and the bulbar network function. The general aim of this project is to delineate the logic of GC-mediated inhibition in the OB, i.e. the functional organisation of synapses onto GCs, allowing anatomical predictions as to how activated glomerular columns interact with each other as well as with different populations of centrifugal inputs, using retrograde viral labelling, large scale volume electron microscopy and synchrotron X-ray tomography. This detailed anatomical analysis will yield input distribution patterns that will then be used to stimulate GCs with multisite 3D uncaging. This approach will allow us to address the question of how local recurrent and centrifugal inputs act in concert to modulate information processing in the OB.