Browsing by Subject "Smell"
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Item Paradoxically Sparse Chemosensory Tuning in Broadly-Integrating External Granule Cells in the Mouse Accessory Olfactory Bulb(2020-05-01T05:00:00.000Z) Zhang, Xingjian; Pfeiffer, Brad E.; Roberts, Todd; Xu, Wei; Bezprozvanny, Ilya; Meeks, Julian P.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.Item Physiology and Circuitry of Bile Acid Detection Within the Accessory Olfactory System(2021-05-01T05:00:00.000Z) Wong, Wen Mai; Lai, Helen; Pfeiffer, Brad E.; Konopka, Genevieve; Meeks, Julian P.The mouse accessory olfactory system (AOS) supports social and reproductive behavior through the sensation of environmental chemosignals. These chemosensory cues provide a vast amount of information that the olfactory systems must then encode and translate into behaviorally relevant outputs. The initial detection of olfactory stimuli in the accessory olfactory system (AOS) is mediated by the vomeronasal sensory neurons (VSNs) in the vomeronasal organ (VNO), which relay the signals to the accessory olfactory bulb (AOB). Impaired vomeronasal signaling results in deficits in social communication and other behaviors. Despite decades of research, our understanding of how odors are encoded and processed within the AOS is still severely limited. For example, the extent to which the AOS discriminates and encodes chemosensory information at the peripheral level of the VNO is currently unknown. Furthermore, how the tuning of VSNs is then translated into a behaviorally relevant representation in the brain is still unclear. Understanding how the AOS processes and encodes chemosensory information will advance our understanding of how external cues can generate internal chemosensory representations that are critical for survival. Sensory adaptation is a source of experience-dependent feedback that impacts responses to environmental cues. In the mammalian main olfactory system (MOS), adaptation influences sensory coding at its earliest processing stages. However, sensory adaptation in the accessory olfactory system (AOS) remains relatively controversial, leaving many aspects of the phenomenon unclear. Thus, I investigated sensory adaptation in vomeronasal sensory neurons (VSNs) using in situ Ca2+ imaging. I found evidence for sensory adaptation in response to the monomolecular ligands, cholic acid (CA) and deoxycholic acid (DCA). These Ca2+ imaging experiments also revealed the presence of a slower form of VSN adaptation that accumulated over dozens of stimulus presentations delivered over tens of minutes. These studies help establish the presence of VSN sensory adaptation and provide a foundation for future inquiries into the molecular and cellular mechanisms of this phenomenon and its impact on mammalian behavior. A growing number of excreted steroids have been shown to be potent AOS cues, including bile acids (BAs) found in feces. As is still the case with most AOS ligands, the specific receptors used by vomeronasal sensory neurons (VSNs) to detect BAs remain unknown. To identify VSN BA receptors, we first performed a deep analysis of VSN BA tuning using volumetric GCaMP6f/s Ca2+ imaging. These experiments revealed multiple distinct populations of BA-receptive VSNs with submicromolar sensitivities. I then developed a new physiology-forward approach for identifying AOS ligand-receptor interactions, which I term Fluorescence Live Imaging for Cell Capture and RNA sequencing, or FLICCR-seq. FLICCR-seq analysis revealed five specific V1R family receptors enriched in BA-sensitive VSNs. These studies introduce a powerful new approach for ligand-receptor matching and reveal biological mechanisms underlying mammalian BA chemosensation. Finally, I've spent the remainder of my thesis laying the groundwork for exploring BA-mediated behaviors and the circuitry of BA information as it travels through the AOS. Importantly, my work opens many avenues for future studies. Here, I show evidence that five specific V1R receptors are BA-sensitive. The identification of ligands that can modulate the activity of orphan VRs is paramount to understanding their function and in turn understanding chemosensation. We now have more tools in the toolbox to understanding and studying the activation of VRs, their signal transduction, and their function.