One of the goals of our lab is to study the role of sensory input on the disruption and recovery 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 superficial tufted cells (TC). We have shown that the axonal projections from these centrally derived TCs give rise to an anatomically based intrabulbar map that is extremely specific, yet is also dynamic and is modulated by olfactory stimuli. Our previous studies demonstrated that loss of odorant-induced activity results in disruption and disorganization of intrabulbar circuitry (Marks et al., 2006), leaving it unclear if proper map organization could ever be restored. Our recent studies have revealed the intrabulbar projection do indeed retain the capacity for circuit and map restoration. Furthermore, using a reversible odor-deprivation model we demonstrated that by returning odorant-induced activity it provided all the information necessary to restore the intrabulbar map (Cummings and Belluscio, J. Neurosci., 2010). These studies also showed that in adults the organization of the glomerular map is less sensitive to odorant induced activity and while activity loss did reduce the size of glomeruli within the map the organization was preserved. In a related set of experiments we also sought to understand the regenerative capacity of the intrabulbar circuitry by following olfactory bulb interneurons which are derived from the subventricular zone (SVZ) and migrate to the bulb via the rostral migratory stream (RMS). These interneurons are the post-synaptic targets of the intrabulbar projections (Liu and Shipley, J. Comp. Neurol., 1994) and thus have direct bearing on the plasticity of the intrabulbar map. To better understand the dynamic basis for their incorporation into the olfactory bulb circuitry we developed an in-vitro slice preparation to track and measure the migration of RMS neuroblast using imaging techniques. These studies found that RMS flow is bi-directional and that BDNF signaling is playing an important regulatory role in the migration of new neurons to the olfactory bulb (Bagley and Belluscio, Neuroscience, 2010). Together these studies help us to better understand the mechanisms that regulate circuit plasticity and repair in the olfactory bulb and possibly throughout the brain as well.

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Budget End
Support Year
1
Fiscal Year
2010
Total Cost
$914,559
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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
Cheng, Ning; Jiao, Song; Gumaste, Ankita et al. (2016) APP Overexpression Causes A?-Independent Neuronal Death through Intrinsic Apoptosis Pathway. eNeuro 3:
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
Xydakis, Michael S; Mulligan, Lisa P; Smith, Alice B et al. (2015) Olfactory impairment and traumatic brain injury in blast-injured combat troops: a cohort study. Neurology 84:1559-67
Saar, Galit; Cheng, Ning; Belluscio, Leonardo et al. (2015) Laminar specific detection of APP induced neurodegeneration and recovery using MEMRI in an olfactory based Alzheimer's disease mouse model. Neuroimage 118:183-92
Steuer, Elizabeth; Schaefer, Michele L; Belluscio, Leonardo (2014) Using the olfactory system as an in vivo model to study traumatic brain injury and repair. J Neurotrauma 31:1277-91
Cheng, Ning; Bai, Li; Steuer, Elizabeth et al. (2013) Olfactory functions scale with circuit restoration in a rapidly reversible Alzheimer's disease model. J Neurosci 33:12208-17
Cheng, Kai; Bai, Li; Belluscio, Leonardo (2011) Fas-associated factor 1 as a regulator of olfactory axon guidance. J Neurosci 31:11905-13
Cheng, Ning; Cai, Huaibin; Belluscio, Leonardo (2011) In vivo olfactory model of APP-induced neurodegeneration reveals a reversible cell-autonomous function. J Neurosci 31:13699-704
Cummings, Diana M; Belluscio, Leonardo (2010) Continuous neural plasticity in the olfactory intrabulbar circuitry. J Neurosci 30:9172-80

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