Heterogeneous monotonic and non-monotonic responses to odor in mitral/tufted glomeruli of the mouse olfactory bulb

Animals can recognize and discriminate between different odors and the same odor over a range of concentrations. Processing within the mouse olfactory bulb (OB) may be involved, yet the underlying mechanisms remain unclear. Each olfactory receptor neuron (ORN) type maps to the OB in olfactory receptor specific channels called glomeruli where they connect with the dendrites of mitral/tufted cells (MTCs), which project their axons to the rest of the brain. Differences between input and output define the functions carried out by a brain region. Using in vivo dual-color 2-photon Ca2+ imaging from the ORNs and MTCs innervating the same glomeruli in the mouse OB, we identified a novel MTC response type with a non-monotonic concentration-response relationship. We used mathematical modeling to demonstrate that non-monotonic response types are consistent with a form of interglomerular processing, which we propose is a mechanism to facilitate odor discrimination and the ability to achieve concentration-invariant odor perception. Graphical AbstractThe olfactory bulb input-output transformation was imaged using dual-color 2-photon imaging. (Top) Cartoon and histological examples of labeling the olfactory bulb input and output using spectrally distinct optical sensors. (Middle) Modeling and experimental work reveal that input neurons that respond with primarily monotonic concentration-response relationships are transformed into a mix of monotonic and non-monotonic responses. (Bottom) Olfactory bulb output state space for a population of 3 glomeruli with exclusively monotonic responses (black), and with both monotonic and non-monotonic responses (red). Each trajectory represents a cloud of points that reflects variations in the fluctuations of molecular components present in natural odor stimuli. Monotonic responses alone cluster together, while multiple response types broaden coverage of MTC state space. Greater coverage of state space makes it easier to discriminate one odor from another, even though the dimension of olfactory bulb state space is larger than 3. Key PointsO_LIAlthough the olfactory bulb is the first stage of olfactory sensory processing, its role in transforming sensory information remains poorly understood. C_LIO_LIDifferent olfactory receptor neuron types map to the olfactory bulb in olfactory receptor specific channels called glomeruli, where they interact with the dendrites of mitral/tufted cells, which project to the rest of the brain. C_LIO_LIWe used dual-color 2-photon Ca2+ imaging to image the input-output transformation olfactory receptor neuron (ORN) and mitral/tufted (MTC) glomeruli across a wide concentration range. C_LIO_LIThe ORN input to all tested glomeruli responded to increasing concentration changes with monotonic increases, while the corresponding MTCs outputs of each glomerulus responded with monotonic and non-monotonic changes. C_LIO_LIThe results were consistent with a mathematical model of the olfactory bulb incorporating feed-forward and lateral inhibition. C_LI