Temporal dynamics of inhalation-linked activity across defined subpopulations of mouse olfactory bulb neurons imaged in vivo

ABSTRACT In mammalian olfaction, inhalation drives the temporal patterning of neural activity that underlies early olfactory processing, and a single inhalation of odorant is sufficient for odor perception. However, how the neural circuits that process incoming olfactory information are activated in the context of inhalation-linked dynamics remains poorly understood. To better understand early olfactory processing in vivo, we used an artificial inhalation paradigm combined with two-photon calcium imaging to compare the dynamics of activity evoked by odorant inhalation across major cell types of the mouse olfactory bulb. Transgenic models and cell-type specific genetic tools were used to express GCaMP6f or jRGECO1a in mitral and tufted cell subpopulations, olfactory sensory neurons and two major juxtaglomerular interneuron classes, and responses to a single inhalation of odorant were compared. Activity in all cell types was strongly linked to inhalation, and all cell types showed some variance in the latency, rise-times and durations of their inhalation-linked response patterns. The dynamics of juxtaglomerular interneuron activity closely matched that of sensory neuron inputs, while mitral and tufted cells showed the highest diversity in dynamics, with a range of latencies and durations that could not be accounted for by heterogeneity in the dynamics of sensory input. Surprisingly, temporal response patterns of mitral and superficial tufted cells were highly overlapping such that these two subpopulations could not be distinguished on the basis of their inhalation-linked dynamics, with the exception of a subpopulation of superficial tufted cells expressing the peptide transmitter cholecystokinin. Overall, these results support a model in which diversity in inhalation-linked patterning of OB output arises first at the level of OSN inputs to the OB and is enhanced by feedforward inhibition from juxtaglomerular interneurons which differentially impacts different subpopulations of OB output neurons.