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 the olfactory maps and is considered to be the basic functional unit of the olfactory bulb. Since the odor column is a vertically oriented translaminar structure that extend from the glomeruli at surface of the bulb to the granule cell layer it is comprised of many cell types including input, output and modulatory neurons. Our goal is to understand how each of these cell types contributes to signal processing within the odor column and how they are involves in olfactory circuit plasticity. Previously we showed that the olfactory bulb maintains a high level of plasticity particularly within the circuitry of the intrabulbar map (reviewed, Cummings and Belluscio, 2008). More, recently we demonstrated that this high level of plasticity is maintained throughout adulthood and that sensory induced activity can be used to organize the connections (Cummings and Belluscio, 2010). Using a genetic approach we have developed a series of transgenic mice that can express different genes within different parts of the olfactory bulb circuitry. These animals will prove invaluable in helping us elucidate both olfactory circuit development and function. In our collaboration with Dr. Nick Ryba's lab at NIDCR we showed that premature expression of odorant receptors in immature OSNs disrupts their projections to the olfactory bulb (Nguyan et al., J. Neurosci., 2010) and are continuing to characterize the effect on other parts of the odor column circuitry. Given that the circuitry of the olfactory bulb undergoes tremendous anatomical change simply in response to the regeneration of interneurons we also established an in vitro brain slice preparation to measure neural reorganization through fluorescent time-lapse imaging (Bagley and Belluscio;2010). In collaboration with Dr. Alan Koretsky's lab in NINDS we are now performing MRI studies in living animals to further measure these changes in response to odorant induced activity. In other studies, we are exploring the role of growth factors in the development of the olfactory bulb circuitry in collaboration with Dr. Carlos Ibanez at the Karolinska Institute, as well as the role of the Mitf1 in collaboration with Dr. Eirkur Steingrimsson at the University of Iceland. Together, these studies have not only revealed new information about the formation of olfactory circuitry but also helped us develop new molecular and functional imaging tools to facilitate future studies.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2011
Total Cost
$1,024,907
Indirect Cost
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State
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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
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
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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