Our lab seeks to understand the development formation and refinement of neural circuits within the mammalian brain. Our current focus is on a defined central circuit within the mouse olfactory bulb (OB) that specifically links iso-functional regions within each bulb. Since olfactory sensory input is organized through a set of stereotyped maps in the medial and lateral bulb understanding the formation of this circuitry and the nature of intrabulbar communication becomes central to understanding olfactory function. Previously we showed that the OB circuitry maintains a high level of plasticity particularly with regard to intrabulbar projections (reviewed, Cummings and Belluscio, 2008). We showed that the intrabulbar map that is mediated by these projections reorganizes its connectivity throughout life in an activity dependent manner. We are now utilizing in vivo time-lapse imaging to determine the precise neuronal subtypes and signaling molecules that regulate intrabulbar plasticity. At a functional level we recently showed that the medial and lateral halves of the OB receive olfactory sensory input that is temporally shifted and is modulated by odorant concentration (Zhou and Belluscio, 2012). Currently, we are using multielectrode recordings coupled with Optogenetic techniques to determine the role of intrabulbar projections in modulating this medial lateral olfactory bulb timing for coding in the pyriform cortex. Through our collaborative efforts with the Ibanez Lab at the Karolinska Institute we have also explored the molecular basis of OB circuit formation. We showed that Glial Derived Neurotrophic Factor (GDNF) is involved in OB development in particular signaling through the GFRa1 receptor (Marks et al., 2012). We are now investigating the role of such factors in intrabulbar plasticity as well.

Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2013
Total Cost
$907,051
Indirect Cost
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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 16:1115-25
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
Cheetham, Claire E J; Park, Una; Belluscio, Leonardo (2016) Rapid and continuous activity-dependent plasticity of olfactory sensory input. Nat Commun 7:10729
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
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
Cheetham, Claire E; Belluscio, Leonardo (2014) Neuroscience. An olfactory critical period. Science 344:157-8
Lodovichi, Claudia; Belluscio, Leonardo (2012) Odorant receptors in the formation of the olfactory bulb circuitry. Physiology (Bethesda) 27:200-12
Bagley, J A; Belluscio, L (2010) Dynamic imaging reveals that brain-derived neurotrophic factor can independently regulate motility and direction of neuroblasts within the rostral migratory stream. Neuroscience 169:1449-61
Chuang, Kai-Hsiang; Belluscio, Leonardo; Koretsky, Alan P (2010) In vivo detection of individual glomeruli in the rodent olfactory bulb using manganese enhanced MRI. Neuroimage 49:1350-6
Nguyen, Minh Q; Marks, Carolyn A; Belluscio, Leonardo et al. (2010) Early expression of odorant receptors distorts the olfactory circuitry. J Neurosci 30:9271-9

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