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UBC Theses and Dissertations

Olfactory receptor neurons persist during extensive remodeling of the olfactory bulb following NMDA-induced excitotoxicity Fung, France W.

Abstract

The olfactory epithelium and bulb are thought to contain neurons that are interdependent for survival, similar to other parts of the developing and mature nervous system, yet both sites have demonstrated distinct cellular plasticity in a variety of lesion models. Here, we have used NMDA-mediated excitotoxicity to specifically remove NMDAR-bearing neurons in the intact olfactory bulb. Here, we show that NMDA infusion induces a wave of apoptosis in multiple neuronal subtypes throughout the mouse olfactory bulb. This is followed by astrogliosis and cavity formation (characteristic of CNS lesion), and extensive rearrangement of both neuronal and glial cytoarchitecture of the olfactory bulb. OB glomeruli undergo extensive synaptic remodeling, with many glomeruli withdrawing into an extensive nerve fibre layer, while others persist and enlarge. Most ORNs survive in the absence of their major target cells, and their glomerular contacts appear to be maintained by a surviving periglomerular neuron population. In the absence of mitral/tufted cells, migrating neuroblasts cease radial migration and become stalled in the granule layer of the olfactory bulb, where they attempt a tissue remodeling response. A subset of ORNs undergoes delayed apoptosis 4 days after lesion, resulting in a small, but sustained, increase in neurogenesis throughout the OE, reflected in an increasing GAP43+ axonal population in the olfactory bulb, even in the absence of all targets in the olfactory bulb other than periglomerular neurons.

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