Using functionally-defined glomeruli to probe circuit function in the mammalian olfactory bulb

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PROJECT SUMMARY We seek to better understand how the brain processes olfactory information by focusing on how circuits of the olfactory bulb control two fundamental aspects of sensory processing: the relationship between sensory input and olfactory bulb output as a function of stimulus intensity, and tuning of response specificity by lateral inhibition. Models of how olfactory bulb circuits mediate these operations exist, but generating and testing rigorous predictions from them has been limited by a lack of understanding of how circuits are organized with respect to olfactory bulb glomeruli. Glomeruli represent individual odorant receptors and so constitute the fundamental unit of information processing at this stage. Our strategy is to overcome this gap by, first, better defining the functional map of odor 'space' across glomeruli of the dorsal olfactory bulb. To achieve this we will functionally define glomeruli in terms of the odorants to which they have maximal sensitivity as well as their relative sensitivities across a carefully-selected odorant panel, yielding the first `odor sensitivity' map of the dorsal olfactory bulb and allowing for the rapid and reliable identification of individual glomeruli across animals. We will use these data to uncover new insights into the organization of glomerular odor maps and to generate a public resource for further exploration by the neuroscience community. We will next use this knowledge to rigorously test alternative models for how specific circuits shape the input-output functions of the olfactory bulb by comparing intensity-response functions of sensory inputs and glomerular outputs and by selectively removing particular interneuron types from the olfactory bulb network. We will also test alternative models for how inhibitory connections between different glomeruli are organized and how they may be shaped by odor experience, using odorants that selectively activate different combinations of identified glomeruli. Our experimental strategy builds on innovative approaches that are key to achieving a new level of understanding of how odor representations are transformed by olfactory bulb circuits. First, we are able to repeatedly identify and target many glomeruli across the dorsal olfactory bulb using a small number of diagnostic odorants and to efficiently map responses to many odorants in a single experiment. Second, we are able to selectively image from sensory inputs to glomeruli, projection neuron outputs from glomeruli, or both simultaneously, allowing us to precisely characterize input-output transformations by olfactory circuits. Finally, we will develop an improved model of the olfactory bulb network that is highly constrained by experimental data and which should lead to new insights into how this network alters odor representations and enable new predictions that can be tested with further circuit manipulations or behavioral assays.