We have developed two extremely powerful genetic techniques that permit us for the first time to manipulate the survival and synaptic transmission of specific subsets of olfactory neurons in a temporally and spatially regulated manner. Our ability to kill or synaptically silence olfactory neurons during embryonic development, early postnatal life as well as adulthood provides us with unprecedented tools and opportunities to dissect the olfactory system as thoroughly as has been accomplished for other sensory systems. The goal of this proposal is to use these two novel and powerful techniques to investigate how precise connections between the periphery and the brain are established and continually maintained to preserve the integrity of the olfactory sensory maps, to examine whether there is modularity in the assembly of these maps and to probe the role of activity-dependent plasticity. Specifically, we wish to determine whether a) the olfactory bulb map is re-established after carefully controlled genetic ablation of all olfactory neurons. b) there is neuronal competition during the formation of the olfactory bulb map. c) synaptic contact between olfactory axons and mitral cells is necessary for the formation and differentiation of the mitral cell dendritic field d) primary olfactory input is required for the formation and maintenance of the olfactory cortex map. e) there is activity dependent competition for targets during the formation and maintenance of the olfactory cortex map. How order emerges in the development of the olfactory maps, while interesting in its own right, may apply broadly to other parts of the brain and provide a general understanding of the development of topographic patterns in brain. Moreover, understanding the mechanisms that underlie the matching patterns of connections from one brain structure to another is fundamental to our understanding of the pathology of neural diseases and may provide valuable insight into the fidelity of synapse formation when stem cells are used to cure neurological disorders.
| Cao, Luxiang; Dhilla, Alefiya; Mukai, Jun et al. (2007) Genetic modulation of BDNF signaling affects the outcome of axonal competition in vivo. Curr Biol 17:911-21 |
| Yu, C Ron; Power, Jennifer; Barnea, Gilad et al. (2004) Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map. Neuron 42:553-66 |
