Our studies center upon a defined central circuit within the mouse olfactory bulb (OB) that is organized into an odor column. The odor column circuitry centers on the glomerulus which receives input directly from olfactory sensory neurons (OSNs) in the nose and sends its output via mitral / tufted cells directly to the olfactory cortex. Studies have shown that the OB circuitry maintains a high level of plasticity and that sensory experience and regeneration play a role in the reorganizing that circuitry (reviewed, Cummings and Belluscio, 2008). Thus, recent work has focused on measuring the anatomical and functional changes within the distinct components of the odor column circuit. Our previous work showed that odorant induced activity can modulate the refinement of OSN axons within the glomerular circuitry (Kerr and Belluscio, 2006). To determine the basis of this plasticity we are now utilizing a transgenic mouse line in which OSN axons and their synaptic terminals are labeled with distinct fluorescent molecules. This enables us to visibly detect changes in connectivity over time and measure those changes in vivo. We are also using a similar time lapse imaging approach combined with static time points to analyze the turnover of interneurons in the OB in response to changes in sensory activity. Studies have shown that sensory deprivation resulting from naris block causes both reorganization and loss of OB interneurons but the mechanistic basis is unclear. Our studies are currently exploring the involvement of microglia both in the pruning and elimination of these OB neurons. At a functional level, we have shown that the medial and lateral halves of an olfactory bulb respond to odorant stimuli with small timing differences that shift with changes in odorant concentration (Zhou and Belluscio, 2012). While timing has been shown to play a critical role in many sensory systems the role of these intrabulbar timing differences remain unclear particularly within the broader context of the network. Thus, we are conducting multi-electrode recording experiments within the OB to determine how changes in odorant concentration affects the broader OB network.

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12
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2014
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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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