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

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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.