Progress in understanding the neurobiological basis of olfaction has been enhanced by development of neuroimaging methods in the olfactory bulb. These methods have provided quite convincing evidence to suggest that information carried by odorant molecules is partially encoded in spatial activity patterns of glomeruli, and significant progress has been made to obtain the structural, functional, and molecular basis of these glomerular patterns. However, noticeable gaps in understanding arise from the absence of full 3D localizations of neural activity in individual glomerulae and the neuroenergetic basis of these maps. The functional MRI (fMRI) method allows 3D mapping with relatively high temporal and spatial resolution. In the previous funding period we developed and applied this technology to the study of olfaction, and we obtained reproducible glomerular level fMRI data at 7T from the rat olfactory bulb. In the present proposal we propose to take advantage of these developments and findings to address the following questions about the functional neuroarchitecture of the bulb. How is information about odorant identity and concentration encoded in the glomerular spatial activity pattern? Is there feedback inhibition of the glomerular and inner layers of the bulb during odorant exposure? What is the neuroenergetic cost of spatial activity patterns in the bulb? This last question is important for understanding olfactory bulb function because our recent 13C studies have shown that neuronal activity is energetically expensive in the cerebral cortex. In this grant we propose to further develop the fMRI methodology to provide glomerular resolution maps with high temporal ana spatial resolution. The fMRI signal will be calibrated and then validated using 13C methods we pioneered in studying the somatosensory cortex to provide quantitative maps of functional neuroenergetics and neuronal activity (as measured by extracellular electrical recordings and Ca2+ imaging of neurotransmitter release at the glomerulus). The 3D maps of individual glomerular function will be used to explore the dependence of the spatial activity patterns on odorant structure, concentration, and the mechanisms of time-dependent adaptation and feedback inhibition on these glomerular patterns. Activity of single glomeruli can help elucidate mechanisms of olfactory processing.
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