Paradoxically Sparse Chemosensory Tuning in Broadly-Integrating External Granule Cells in the Mouse Accessory Olfactory Bulb

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2020-05-01T05:00:00.000Z

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Zhang, Xingjian

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Abstract

Most terrestrial animal species heavily rely on non-volatile chemosignals for conspecific and heterospecific communication. The sensory system responsible for detecting such signals is especially important in guiding animal behavior. Such sensory system in rodents is called accessory olfactory system (AOS). The chemostimulation detection is done by the vomeronasal sensory neurons in the vomeronasal organ (VNO), with their ligand-specific receptors. The electrophysiological signals generated here are then projected to the accessory olfactory bulb (AOB), where the local circuit performs preliminary filtering to the signal. GABAergic interneurons are known to exert their signal sculpturing effect onto principal cells in many brain areas. However, the roles of the AOB GABAergic interneurons are poorly understood. Here, I focus on one genetically defined subtype of GABAergic interneuron, called external granule cell (EGC). Using fast non-ratiometric Ca2+ indicator GCaMP6f specifically expressed in target cell populations on a specialized ex vivo preparation that preserves the functional connections of VNO and AOB, I characterized and compared the tuning properties of EGC and the mitral cells (MC). EGCs show generally narrow tuning preferences towards naturalistic stimulation such as mouse fecal extract and urinal extract, but MCs are much more excitable upon monomolecular sulfated steroid ligands. The result on its appearance contradicts the integrative model as indicated by the circuitry architecture, in which individual EGC broadly connects with MCs by dendrodendritic reciprocal synapses. One explanation is that EGC activation has relatively high threshold. In the presence of sulfated steroids, the excitatory inputs from the activated MCs may not be strong enough to elicit action potentials. Nevertheless, such inputs should be reflected by membrane potential recording of EGCs, in the form of subthreshold depolarizations. To verify this hypothesis, I performed ex vivo electrophysiological recording on EGCs upon the chemostimulation. As expected, subthreshold activities were reliably triggered by sulfated steroid ligands, displaying a 'tuning' profile indistinguishable from that of MCs as indicated by GCaMP6f imaging. AOB granule cells are widely believed to be the information gating module under various behavioral contexts. This unexpected discovery of EGCs might suggest a unique information processing logic of AOS fitting the purpose of rodent social communication.

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The file named "ZHANG-PRIMARY-2022-1.pdf" is the primary dissertation file. Seven (7) supplemental video files are also available and may be viewed individually.

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