Our lab studies the role of sensory input on the formation and refinement of neural circuits within the olfactory system. Our current focus is on understanding the basis of a robust form of cellular plasticity exhibited by a class of neurons in the olfactory bulb called external tufted cells which give rise to an intrabulbar map and ask how this plasticity is modulated by olfactory stimuli. We have previously described the anatomical basis of this plasticity showing that odorant induced activity is necessary for the development and maintenance of the intrabulbar map which has no critical period (Marks et al., 2006). We are now extending these studies to determine if the organization of the intrabulbar map can be restored once it is disrupted. In addition, we are investigating the functional role of intrabulbar projections in the olfactory process through both electrophysiological and behavioral experiments. In one study we developed a slice preparation that maintains intrabulbar projection intact which enabled us to determine that they can function as a timing-based gate to modulate olfactory bulb output (Zhou and Belluscio, 2008). We are now investigating this role in vivo. Finally, at a molecular level we have developed a genetic means to over-express any individual odorant receptor throughout the olfactory epithelium thus enabling us to activate the entire olfactory system with a single odorant (Nguyan et al., 2007). This strategy will enable us to study the developmental and functional affects of broad odorant induced stimulation on the circuitry of the olfactory system.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2009
Total Cost
$1,327,686
Indirect Cost
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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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