Our lab seeks to understand the development, formation, and refinement of neural circuits within the olfactory system. Our current focus has been on the organizational maps of the olfactory system and in particular the circuitry of the odor column which connects these maps and is considered by many to be the basic functional unit of the olfactory bulb. An odor column is a vertically oriented translaminar structure that extend from the surface of the bulb to the granule cell layer and consists of a glomerulus together its associated output and modulatory components below. Studies have shown that the glomerular and intrabulbar maps of the olfactory bulb are in part organized by the expression of odorant receptors in the olfactory sensory neurons (OSNs) of the nasal epithelium (Wang et al., Cell, 1998, Belluscio et al., Nature, 2002). Thus, to study the process by which odorant receptors help guide the formation of the odor column circuitry we have developed a transgenic method to express specific odorant receptors throughout the olfactory epithelium (Nguyan et al., Cell, 2007). Our recent experiments in conjunction with the Ryba lab in NIDCR we have shown that broad early expression of a single odorant receptor in immature OSNs disrupts the glomerular map and results in distorted activity patterns throughout the olfactory bulb (Nguyan et al., J. Neurosci., 2010). It is still unclear what the consequences of this glomerular disruption are on the organization of the intrabulbar map. In a second set of studies conducted in collaboration with the Koretsky lab in NINDS we have successfully detected the activation and downstream signaling patterns elicited by individual odorants in live anesthetized mice using Manganese-Enhanced MRI (MEMRI). These experiments demonstrated that MEMRI can be used to image odorant-induced activity throughout the entire olfactory bulb at the resolution of a single glomerulus (Chueng et al., Neuroimage, 2009;2010). In addition, since MEMRI is essentially non-invasive we use it to re-image the same olfactory bulb circuitry multiple times to study changes associated with odorant induced activity. Together, these studies have not only revealed new information about the formation of olfactory circuitry but also helped to develop new molecular and functional imaging tools that will facilitate our future studies of olfactory plasticity within that circuitry.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2010
Total Cost
$914,559
Indirect Cost
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State
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Pothayee, Nikorn; Cummings, Diana M; Schoenfeld, Timothy J et al. (2017) Magnetic resonance imaging of odorant activity-dependent migration of neural precursor cells and olfactory bulb growth. Neuroimage 158:232-241
Fan, Jianguo; Jia, Li; Li, Yan et al. (2017) Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse. Proc Natl Acad Sci U S A 114:E4271-E4280
Cheetham, Claire E J; Park, Una; Belluscio, Leonardo (2016) Rapid and continuous activity-dependent plasticity of olfactory sensory input. Nat Commun 7:10729
Grier, Bryce D; Belluscio, Leonardo; Cheetham, Claire E J (2016) Olfactory Sensory Activity Modulates Microglial-Neuronal Interactions during Dopaminergic Cell Loss in the Olfactory Bulb. Front Cell Neurosci 10:178
D'Hulst, Charlotte; Mina, Raena B; Gershon, Zachary et al. (2016) MouSensor: A Versatile Genetic Platform to Create Super Sniffer Mice for Studying Human Odor Coding. Cell Rep 16:1115-1125
Cheetham, Claire E J; Grier, Bryce D; Belluscio, Leonardo (2015) Bulk regional viral injection in neonatal mice enables structural and functional interrogation of defined neuronal populations throughout targeted brain areas. Front Neural Circuits 9:72
Cheetham, Claire E; Belluscio, Leonardo (2014) Neuroscience. An olfactory critical period. Science 344:157-8
Cummings, Diana M; Snyder, Jason S; Brewer, Michelle et al. (2014) Adult neurogenesis is necessary to refine and maintain circuit specificity. J Neurosci 34:13801-10
Marks, Carolyn; Belluscio, Leonardo; Ibáñez, Carlos F (2012) Critical role of GFR?1 in the development and function of the main olfactory system. J Neurosci 32:17306-20
Zhou, Zhishang; Belluscio, Leonardo (2012) Coding odorant concentration through activation timing between the medial and lateral olfactory bulb. Cell Rep 2:1143-50

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