The general goal of my lab is to understand the molecular and functional mechanisms that generate the precise neural patterns of the olfactory bulb and how those patterns change during learning. In mammals, the olfactory system detects and discriminates tens of thousands of odorants using a large family of receptors expressed by sensory neurons in the nasal epithelium. Over a decade ago, molecular experiments established that axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli generating two mirror-symmetric maps of odorant receptor projections on the surface of each bulb. This organization is a feature not found in the initial topographic maps of other sensory systems. My research focuses on elucidating the synaptic circuitry that is established during initial bulb development, and defining the factors that cause its reorganization during neonatal learning. We have used an in-vivo optical imaging technique called Intrinsic Signal Imaging (ISI), to acquire a series of odorant induced functional maps showing the local activation patterns in the olfactory bulbs. Define the functional organization of the bulbs allowed us to draw parallels to the organizational properties of the previously defined molecular maps. By then utilizing this approach on genetically modified mice we were able to establish the first direct link between functional and molecular maps. Through these studies we also uncovered an exciting new intrabulbar map consisting of a precise point-to-point topographic link between the two mirror-symmetric olfactory bulb maps leading to the hypothesis of a unified bulbar map. Thus, rather than each olfactory bulb containing two mirror-symmetric maps, we propose that the olfactory bulb actually contains a single integrated map in which isofunctional odor columns are connected through an intrabulbar link, analogous to the specific horizontal connections linking iso-orientation columns in primary visual cortex. Currently, I am extending this work at the NIH using multi-photon laser scanning microscopy to perform in-vivo studies on the formation of olfactory bulb circuits as they are being established during bulb development. The three main aspects to my research plan are: 1) to assess the anatomical formation of specific neural circuits through repeated long-term imaging of fluorescently tagged neurons in the olfactory bulb; 2) to perform electrophysiological dual recordings from isofunctional glomerular pairs to assess the interactive properties of the two mirror symmetric maps, and 3) to train neonatal pups through olfactory conditioning and determine the morphological and physiological changes to olfactory circuits using a combined imaging and electrophysiological approach. As olfactory dysfunction is commonly associated with many neurological disorders this work will certainly have clinical application.
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| Nguyen, Minh Q; Zhou, Zhishang; Marks, Carolyn A et al. (2007) Prominent roles for odorant receptor coding sequences in allelic exclusion. Cell 131:1009-17 |
| Kerr, Mariel A; Belluscio, Leonardo (2006) Olfactory experience accelerates glomerular refinement in the mammalian olfactory bulb. Nat Neurosci 9:484-6 |
| Marks, Carolyn A; Cheng, Kai; Cummings, Diana M et al. (2006) Activity-dependent plasticity in the olfactory intrabulbar map. J Neurosci 26:11257-66 |
| Lodovichi, Claudia; Belluscio, Leonardo; Katz, Lawrence C (2003) Functional topography of connections linking mirror-symmetric maps in the mouse olfactory bulb. Neuron 38:265-76 |
