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8. BBS4 is required for intraflagellar transport coordination and basal body number in mammalian olfactory cilia.

Author

Uytingco, Cedric R., Williams, Corey L., Chao Xie, Shively, Dana T., Green, Warren W., Ukhanov, Kirill, Zhang, Lian, Nishimura, Darryl Y., Sheffield, Val C., and Martens, Jeffrey R.

Subjects
CILIA & ciliary motion, OLFACTORY receptors, GENETIC mutation
Abstract

Bardet-Beidl syndrome (BBS) manifests from genetic mutations encoding for one or more BBS proteins. BBS4 loss impacts olfactory ciliation and odor detection, yet the cellular mechanisms remain unclear. Here, we report that Bbs4-/- mice exhibit shorter and fewer olfactory sensory neuron (OSN) cilia despite retaining odorant receptor localization. Within Bbs4-/- OSN cilia, we observed asynchronous rates of IFT-A/B particle movements, indicating miscoordination in IFT complex trafficking. Within the OSN dendritic knob, the basal bodies are dynamic, with incorporation of ectopically expressed centrin-2 and γ-tubulin occurring after nascent ciliogenesis. Importantly, BBS4 loss results in the reduction of basal body numbers separate from cilia loss. Adenoviral expression of BBS4 restored OSN cilia lengths and was sufficient to re-establish odor detection, but failed to rescue ciliary and basal body numbers. Our results yield a model for the plurality of BBS4 functions in OSNs that includes intraciliary and periciliary roles that can explain the loss of cilia and penetrance of ciliopathy phenotypes in olfactory neurons. [ABSTRACT FROM AUTHOR]

Published
2019
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11. The neuroanatomical organization and chemosensory response characteristics of the olfactory bulb in the sea lamprey (Petromyzon marinus)

Author

Green, Warren W.

Subjects
nervous system, Neurobiology, Physiology, Neurosciences, sense organs
Abstract

Olfactory information is utilized for a variety of behaviours including feeding, migration and spawning. The olfactory bulb is the initial site of odour information processing in the central nervous system. The OB organizes this information along parallel processing pathways using topographic and temporal coding. In general, little is known about the neural substrate involved in transforming olfactory information into behavioural responses. In the sea lamprey ( Petromyzon marinus ) the responses of olfactory sensory neurons in the peripheral olfactory organ are transmitted along two distinct pathways to the medial and non-medial regions of the OB. The neural substrate for olfactory-locomotor transformation was recently identified in the sea lamprey, and demonstrated that projection neurons (PNs) in the medial OB region initiated movements by connecting to locomotor control centers. In contrast, PNs in the non-medial OB region projected to forebrain regions including the pallium. This thesis examines previously unknown anatomical and physiological characteristics of PNs in these medial and non-medial OB regions and relates the findings to these functionally distinct parallel output pathways. The medial PNs were anatomically isolated within the glomerular neuropil, exhibited varied somal shape, and had larger somata than non-medial PNs. Furthermore, the bulbar region containing these medial PNs responded to several different classes of odours with local field potentials (LFPs) being a mixture of transient and sustained responses and relatively short multiunit responses. The somata of non-medial PNs were below the glomerular neuropil and also exhibited varied shapes, but were smaller than the somata of the medial PNs. The LFP and multiunit recordings suggested that within the non-medial OB region, the dorsal territory responded differentially to lamprey sex pheromones and migratory pheromones while lateral recordings exhibited sustained LFP responses and long multiunit responses largely to basic amino acids. These findings suggest that neural organization in the medial OB may be optimized for the initiation of olfactory-locomotor movements in response to diverse odours, while the nonmedial regions exhibit odour specificity and may be optimized for other functional processes such as odour information integration.

Published
2013

13. cProgress towards the development of a chemosensory-based biotic ligand model in fathead minnows (Pimephales promelas) and wild yellow perch (Perca flavescens)

Author

Green, Warren W., Wood, C.M., Pyle, G.G., and Biology

Subjects
Biology
Abstract

Elevated metal concentrations in the aquatic environment may pose a threat to fishes through acute lethal and chronic sub-lethal exposures. To assess the impact of anthropogenic metal contamination on aquatic fauna the Biotic Ligand Model (BLM), a model based on metal-binding to the gills, is now considered to be the best approach for predicting site-specific metal toxicity. The olfactory epithelium (OE) of fishes is exposed directly to the aquatic environment and is vulnerable to waterborne exposures to sublethal metal concentrations. These exposures have been shown to impair the olfactory function of fishes. The goal of this thesis was to begin the development of a chemosensory-based BLM (cbBLM) to predict sub-lethal metal toxicity using laboratory based experiments with fathead minnows (Pimephales promelas, FHM) and yellow perch (Percaflavescens, YP), the latter chronically exposed to metals in the wild. Our results demonstrate that Cu and Cd binding to the OE of fathead minnows was saturable and that increasing waterborne Ca decreases metal accumulation in the OE. The binding of Cd to the OE of wild yP was saturable but the binding of Cu was not. Acute exposure of the OE to Cu impaired peripheral olfactory function in FHM as demonstrated by a decreased electrophysiological response but this was not observed for exposures to Cd. Moreover, the peripheral and central olfactory system functions of chronically metal-exposed wild YP were also impaired as indicated by an elevated electrophysiological response and a lack of behavioural response to conspecific skin extracts. This is the first study to examine the binding characteristics of Cu and Cd to the OE of fishes and to relate this metal accumulation in the OE to the impairment of peripheral olfactory function. This information can now be used to begin development of a cbBLM. A cbBLM would use metal-OE binding constants, site-specific water chemistry, and ethological or ecological endpoints. Such models would be useful in devising environmental regulations to predict and therefore prevent chronic, sub-lethal metal toxicity in fishes and improve ecological risk assessment. Master of Science (MS)

Published
2007

18. The Neuroanatomical Organization of Projection Neurons Associated with Different Olfactory Bulb Pathways in the Sea Lamprey, Petromyzon marinus.

Author

Green, Warren W., Basilious, Alfred, Dubuc, Réjean, and Zielinski, Barbara S.

Subjects
*SEA lamprey, *NEUROANATOMY, *OLFACTORY bulb, *INTERNEURONS, *SENSORY neurons, *BRAIN anatomy, *CEREBRAL cortex
Abstract

Although there is abundant evidence for segregated processing in the olfactory system across vertebrate taxa, the spatial relationship between the second order projection neurons (PNs) of olfactory subsystems connecting sensory input to higher brain structures is less clear. In the sea lamprey, there is tight coupling between olfaction and locomotion via PNs extending to the posterior tuberculum from the medial region of the olfactory bulb. This medial region receives peripheral input predominantly from the accessory olfactory organ. However, the axons from olfactory sensory neurons residing in the main olfactory epithelium extend to non-medial regions of the olfactory bulb, and the non-medial bulbar PNs extend their axons to the lateral pallium. It is not known if the receptive fields of the PNs in the two output pathways overlap; nor has the morphology of these PNs been investigated. In this study, retrograde labelling was utilized to investigate the PNs belonging to medial and non-medial projections. The dendrites and somata of the medial PNs were confined to medial glomerular neuropil, and dendrites of non-medial PNs did not enter this territory. The cell bodies and dendrites of the non-medial PNs were predominantly located below the glomeruli (frequently deeper in the olfactory bulb). While PNs in both locations contained single or multiple primary dendrites, the somal size was greater for medial than for non-medial PNs. When considered with the evidence-to-date, this study shows different neuroanatomical organization for medial olfactory bulb PNs extending to locomotor control centers and non-medial PNs extending to the lateral pallium in this vertebrate. [ABSTRACT FROM AUTHOR]

Published
2013
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19. The Neuroanatomical Organization of Projection Neurons Associated with Different Olfactory Bulb Pathways in the Sea Lamprey, Petromyzon marinus.

Author

Green, Warren W., Basilious, Alfred, Dubuc, Réjean, and Zielinski, Barbara S.

Subjects
SEA lamprey, NEUROANATOMY, OLFACTORY bulb, INTERNEURONS, SENSORY neurons, BRAIN anatomy, CEREBRAL cortex
Abstract

Although there is abundant evidence for segregated processing in the olfactory system across vertebrate taxa, the spatial relationship between the second order projection neurons (PNs) of olfactory subsystems connecting sensory input to higher brain structures is less clear. In the sea lamprey, there is tight coupling between olfaction and locomotion via PNs extending to the posterior tuberculum from the medial region of the olfactory bulb. This medial region receives peripheral input predominantly from the accessory olfactory organ. However, the axons from olfactory sensory neurons residing in the main olfactory epithelium extend to non-medial regions of the olfactory bulb, and the non-medial bulbar PNs extend their axons to the lateral pallium. It is not known if the receptive fields of the PNs in the two output pathways overlap; nor has the morphology of these PNs been investigated. In this study, retrograde labelling was utilized to investigate the PNs belonging to medial and non-medial projections. The dendrites and somata of the medial PNs were confined to medial glomerular neuropil, and dendrites of non-medial PNs did not enter this territory. The cell bodies and dendrites of the non-medial PNs were predominantly located below the glomeruli (frequently deeper in the olfactory bulb). While PNs in both locations contained single or multiple primary dendrites, the somal size was greater for medial than for non-medial PNs. When considered with the evidence-to-date, this study shows different neuroanatomical organization for medial olfactory bulb PNs extending to locomotor control centers and non-medial PNs extending to the lateral pallium in this vertebrate. [ABSTRACT FROM AUTHOR]

Published
2013
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