Evidence that interglomerular inhibition generates non-monotonic concentration-response relationships in...

The role of intra- and interglomerular networks in the olfactory bulb (OB) in transforming olfactory receptor neuron (ORN) input across concentration changes remains poorly understood. We addressed this question by implementing a mathematical model of the OB input-output transformation in which the output of each glomerulus is a function of its ORN input, local and lateral inhibition. The model produced outputs with concentration-response relationships that depended on the input ORN Hill coefficient and half-activation value. Some glomeruli responded with monotonic increases or decreases, while others responded with non-monotonic decreases then increases or increased then decreased. The model yielded several novel predictions that challenged recent findings in the field, including the existence of an abundance of non-monotonic responses and that inhibition across the interglomerular network should increase with excitation. We tested these predictions using single and dual-color in vivo 2-photon Ca²⁺ imaging from ORN and MTC glomeruli in awake mice. MTC glomeruli responded to odors with monotonic and non-monotonic concentration-response relationships in an odor-specific manner. Notably the mean excitation and suppression across the glomerular population were significantly correlated with one another and half of the MTC glomeruli exhibited some degree of non-monotonicity. The magnitude of non-monotonicity in MTC glomeruli was significantly correlated with the affinity of its ORN input and decreasing MTC glomeruli were innervated by low affinity or non-responsive ORN input. The results support a model in which rising levels of local and lateral inhibition will generate heterogeneous concentration-response relationships, which we propose will facilitate odor discrimination.