Our incomplete understanding of the brain makes it challenging to understand the mechanisms that underlie sensory deficits and other psychiatric disorders. The olfactory system is an established model for understanding the basic mechanisms of sensory processing, although its specific role(s) in olfactory processing and perception remain unclear. In the olfactory bulb, thousands of olfactory receptor neurons each expressing the same receptor protein converge onto one or two regions of bulb neuropil called glomeruli. There these cells synapse onto the apical dendrites of a few dozen mitral and tufted cells which only innervate that glomerulus, and whose axons provide all of the output to higher brain regions. Thus, the bulb?s input and output are defined anatomically and they spatially overlap in glomeruli. This input-output transformation is shaped by more than 20 different interneuron cell types and feedback from several brain regions. Decades of studying the bulb has led to a number of suggestions that its complex synaptic network may be involved in generating olfactory perceptions like odorant recognition, discrimination and adaptation. The goal of this project is to define the role of the olfactory bulb in olfactory perception, and to understand the mechanisms that underlie those functions. Comparing the signals from the olfactory receptor neuron input and the mitral and tufted cell output can provide definitive statements about the information transformations that occur in the olfactory bulb, and will guide further studies of its synaptic network. We have developed a novel imaging approach to determine this input-output transfer function by comparing the activity signals of both the input and the output of individual glomeruli using voltage and calcium sensors. Our preliminary data using this approach revealed that the glomerular output maps and signal amplitude were much less sensitive to changes in odorant concentration than the input maps. This result suggests that the olfactory bulb contributes to the perception of concentration invariance (i.e., that an odorant is considered the same over a range of concentrations). Here we propose to use our approach to examine the role of the olfactory bulb in an additional olfactory perceptual dimension, and to begin to investigate the mechanism(s) behind these transformations. We will image the voltage or calcium response of the glomerular olfactory receptor neuron input, and the glomerular or individual mitral and tufted cell output in each of these aims. These experiments will generate the first mapping of the glomerular input maps onto the glomerular output maps. At the same time we will optimize our approach for comparing output with input. We expect that our approach will have application to other brain regions.
Compromised olfactory function is associated with the aging process, as well as a number of human diseases including Alzheimers and Parkinsons (65, 66). Understanding the mechanisms that underlie these deficits is difficult, in part due to an incomplete understanding of how neural circuits generate perception. The proposed experiments will begin to characterize the neuronal substrates that generate olfactory perception.
|Sepehri Rad, Masoud; Choi, Yunsook; Cohen, Lawrence B et al. (2017) Voltage and Calcium Imaging of Brain Activity. Biophys J 113:2160-2167|
|Storace, Douglas A; Cohen, Lawrence B (2017) Measuring the olfactory bulb input-output transformation reveals a contribution to the perception of odorant concentration invariance. Nat Commun 8:81|