Browsing by Subject "Olfactory Bulb"
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Item Encoding and Processing of Accessory Olfactory System Odorants(2017-11-02) Doyle, Wayne Ian; Roberts, Todd; Meeks, Julian P.; Gibson, Jay R.; Kavalali, Ege T.; Smith, Dean P.The accessory olfactory system is a mouse olfactory subsystem dedicated to the processing of nonvolatile odors originating from the excretions of other animals. Accessory olfactory system activity drives behaviors critical for mouse survival such as mating, aggression, and predator avoidance. Odorants are detected by sensory neurons in a specialized structure called the vomeronasal organ, and these neurons project to the accessory olfactory bulb. The accessory olfactory bulb is the first site of information integration and processing within the accessory olfactory system, and this processing can be regulated by noradrenaline and other neuromodulators. Despite years of targeted research, there are only a few known ligands for this system limiting our ability to understand how odorants are processed. Part of my thesis has focused on the discovery of novel ligands for this system. I discovered that feces are a novel and potent source of accessory olfactory system odorants. Fecal-driven responses in the accessory olfactory bulb are unique from other known odorant sources and exhibit sex-selectivity, indicating that feces are a potentially rich source of information for the mouse. I determined that bile acids, which vary in identity and concentration by both sex and species, are one class of fecal chemosignals. Accessory olfactory bulb responses to bile acids show patterns of overlapping and specific activity, supportive of a bile acid combinatorial code. During my thesis I have also studied the role of noradrenaline on stimulus processing in the accessory olfactory bulb. I found that noradrenaline has different effects on spontaneous and stimulus-evoked activity. In a small subset of cells noradrenaline increases spontaneous activity, while the majority of cells show suppressed stimulus-evoked activity. This suppression is not consistent across stimulus responses. Some responses are immediately suppressed; some require multiple exposures to stimuli, while others are completely resistant to noradrenaline. Theses results indicate that noradrenaline can have heterogeneous and nuanced actions on accessory olfactory bulb activity.Item Investigating Experience-Dependent Plasticity in the Accessory Olfactory Bulb(2018-04-03) Cansler, Hillary Lauren; Roberts, Todd; Meeks, Julian P.; Huber, Kimberly M.; Monteggia, LisaChemosensory information processing in the mouse accessory olfactory system (AOS) guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC-interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit. Here, we describe a population of AOB internal granule cells (IGCs) that upregulate expression of the immediate early gene Arc following the resident-intruder paradigm in an AOS-dependent manner. Targeted electrophysiological studies revealed that Arc-expressing IGCs in acute AOB slices from resident males displayed stronger excitation than non-expressing neighbors when sensory inputs are stimulated. The increased excitability of Arc-expressing IGCs was not correlated with changes in the strength or number of excitatory synapses with MCs, but was instead associated with increased intrinsic excitability and decreased HCN channel-mediated IH currents. Consistent with increased inhibition by IGCs, MCs responded to sensory input stimulation with decreased depolarization and spiking following resident-intruder encounters. Different populations of IGCs are activated following exposure to males and females, suggesting they are activated in an input-specific fashion. We also describe multiple behavioral paradigms that have been designed to assay social recognition following resident-intruder behavior in conjunction with in vivo manipulation of Arc-expressing IGCs. Together, these results reveal that non-mating behaviors drive AOB inhibitory plasticity, and indicate that increased MC inhibition involves intrinsic excitability changes in Arc-expressing interneurons.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.