Much of our work is focused on the columnar circuitry of the olfactory bulb (OB) and trying to understand the factors that drive its organization and function. Previous work has shown that the neurons within an olfactory bulb odor column exhibit a high level of plasticity with many of the components capable of continuous regeneration. Recently we have been concentrating on three broad factors that seem to play an interrelated function in organizing and maintaining OB column organization: sensory activity, network plasticity and neuronal regeneration. We have found that direct perturbation or modulation of any one of these factors induces alteration in the other two. Using naris occlusion we previously showed that blocking olfactory sensory activity causes disruption of the OB intrabulbar network as well as loss of regenerating interneurons. In a complementary study we also showed that specific elimination of adult born interneurons also produces a disruption of intrabulbar connectivity. Currently we are exploring the role of odorant induced activity patterns both spatial and temporal patterns in organizing and maintaining the OB network. In a parallel study we are using in vivo imaging to measure activity dependent changes in the OB glomerular network, which is situated at the apex of the odor column, and find that sensory activity plays a very direct role in modulating synaptic dynamics. Current efforts are centered on the functional and behavioral related role of this synaptic plasticity. Through collaborations we continue to utilize techniques such as MRI to study OB network plasticity in live intact animals. We have recently incorporated Micron-sized Iron-oxide Particles with MRI to detect the migration of neuroblasts from the subventricular zone to the OB and measure the flow rate in intact animals. We are now determining the affect of sensory activity in modulating the migration and integration of these new neurons in the OB. Together these studies center on better understanding the link between sensory activity, network plasticity and neuronal regeneration in the olfactory system.

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13
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2015
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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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