The olfactory system provides a uniquely powerful environment in which to explore sensory plasticity in mammals, because the earliest central processing in the olfactory system takes place in the glomeruli of the olfactory bulb, a structure that is physically and optically accessible in vivo in animal models, and because recent advances in molecular genetic technology have produced excellent experimental tools for studies in this area. Using a combination of molecular genetic tools and in vivo optical imaging techniques, I have recently shown that the olfactory system exhibits rapid feedback presynaptic inhibition of transmitter release from the olfactory nerve. I hypothesize that the rapid plasticity of this circuit provides adaptive gain control for the primary sensory input from the nose, and thus plays a major role in the encoding of odorant concentration and the perception of odor intensity. Moreover, preliminary data suggest that this inhibitory circuitry may change over time to accommodate changes in the olfactory environment. The first aim of these experiments is to test the hypothesis that this presynaptic modulation of primary sensory input to the olfactory bulb contributes to the encoding of odor concentration. The second aim of these experiments is to use optical imaging techniques to test the hypothesis that changes in sensory environment induces plasticity in the representation of odors at the input to the olfactory bulb. The final aim of these experiments is to use behavioral assays to test how this plasticity affects the perception of odor quality and intensity. Relevance to Public Health: Mammalian sensory systems constantly change to adapt to their environment and experience. While adaptation in some sensory organs is well understood, much less is known about how circuitry in the brain changes to handle different sensory situations. Basic research into this question is needed to better inform the treatment of patients with sensory problems and to enhance the development of artificial sensors and other potential therapies. [unreadable] [unreadable] [unreadable] [unreadable]