Our lab seeks to understand the development, formation, and refinement of neural circuits within the olfactory system. Our current focus has been on the organizational maps of the olfactory system and in particular the circuitry of the odor column, which connects the olfactory maps and is considered to be the basic functional unit of the olfactory bulb. Since the odor column is a vertically oriented, translaminar structure that extends from the glomeruli at surface of the bulb to the granule cell layer it is comprised of many cell types including input, output and modulatory neurons. Our goal is to understand how each of these cell types contributes to signal processing within the odor column and how they are involves in olfactory circuit plasticity. Previously we showed that the olfactory bulb maintains a high level of plasticity particularly within the circuitry of the intrabulbar map (reviewed, Cummings and Belluscio, 2008). We also showed that this high level of plasticity is maintained throughout adulthood and that sensory induced activity is continuously re-organizing the connections. Our recent findings demonstrate that broad non-specific neural activity can suppress postnatal refinement of the intrabulbar map and also disrupt the organization of a fully matured map. Normal odorant induced activity can again restore organization but do so in conjunction with the interneurons of the bulb. Functional studies in the olfactory bulb have revealed that the odorant stimuli activate the olfactory bulb with different spatio-temporal patterns that distinguish the medial and lateral halves of the bulb. We are now determining the purpose of this medial lateral distinction. Using a genetic approach we have developed a series of transgenic mice that can eliminate different parts of the olfactory bulb circuitry. These animals will prove invaluable in helping us elucidate both olfactory circuit development and function. In our collaboration with Dr. Nick Ryba's lab at NIDCR we showed that premature expression of odorant receptors in immature OSNs disrupts their projections to the olfactory bulb and are continuing to characterize the effects on other parts of the odor column circuitry. Since the circuitry of the olfactory bulb undergoes continuous anatomical change simply due to the regeneration of interneurons, we have established a collaboration with Dr. Alan Koretsky's lab in NINDS to use MRI time-lapse imaging to measure these changes in living animals. In other studies, we are exploring the role of growth factors in the development of the olfactory bulb circuitry in collaboration with Dr. Carlos Ibanez at the Karolinska Institute and also trying to understand the axonal signaling of odorant receptors with Dr. Claudia Lodovichi at the VIMM (reviewed, Lodovichi and Belluscio, 2012). Together these studies have provided a better understanding of olfactory circuit formation and also helped us develop new molecular and functional imaging tools to facilitate future studies in neural development.
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