Effect of Sniffing on the Temporal Structure of Mitral/Tufted Cell Output from the Olfactory Bulb

Abstract

Neural activity underlying odor representations in the mammalian olfactory system is strongly patterned by respiratory behavior; these dynamics are central to many models of olfactory information processing. We have previously found that sensory inputs to the olfactory bulb change both their magnitude and temporal structure as a function of sniff frequency. Here, we asked how sniff frequency affects responses of mitral/tufted (MT) cells – the principal olfactory bulb output neuron. We recorded from MT cells in anesthetized rats while reproducing sniffs recorded previously from awake animals and varying sniff frequency. The dynamics of a sniff-evoked response were consistent from sniff to sniff but varied across cells. Compared to the dynamics of receptor neuron activation by the same sniffs, the MT response was shorter and faster, reflecting a temporal sharpening of sensory inputs. Increasing sniff frequency led to moderate attenuation of MT response magnitude and significant changes in the temporal structure of the sniff-evoked MT cell response. Most MT cells responded with a shorter duration and shorter rise-time spike burst as sniff frequency increased, reflecting increased temporal sharpening of inputs by the olfactory bulb. These temporal changes were necessary and sufficient to maintain respiratory modulation in the MT cell population across the range of sniff frequencies expressed during behavior. These results suggest that the input-output relationship in the olfactory bulb varies dynamically as a function of sniff frequency, and that one function of the postsynaptic network is to maintain robust temporal encoding of odor information across different odor sampling strategies.

Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb

“…Naturalistic "sensory" inputs to the models consisted of dynamic synaptic inputs that were derived from odorant-evoked ORN presynaptic calcium signals during natural sampling (i.e., "sniffing") of odorants Carey and Wachowiak 2011). Finally, model output (in the form of MC spiking patterns) was tuned by varying synaptic strength parameters (see MATERIALS AND METHODS) and evaluated by comparison to an experimental dataset consisting of extracellular recordings from presumptive MCs responding to odorants sampled at 1 Hz with the same naturalistic waveforms used to activate ORN inputs (Carey and Wachowiak 2011). Thus model construction and evaluation were both constrained by experimental data.…”

“…Dynamic sensory inputs to all model circuits were derived from ORN responses recorded from anesthetized rats using published data taken from calcium imaging from ORN presynaptic terminals (Carey and Wachowiak 2011), in which odorants were naturalistically sampled using a "sniff playback" approach to reproduce intranasal pressure transients generated (and previously recorded from) awake, head-fixed rats (Cheung et al 2009). A total of 25 ORN input traces were used, with each trace representing the presynaptic calcium signal imaged from a distinct glomerulus.…”

“…Sniff-triggered spike time histograms [peristimulus time histograms (PSTHs), bin size, 20 ms] were generated for each model MC, and temporal response parameters (peak firing rate, response duration, response latency) were measured from a double-sigmoid curve fit to each PSTH, as described previously for experimental data (Carey and Wachowiak 2011). For visual comparison of model and experimental MC response dynamics, for each unit instantaneous firing rate was calculated from each interspike interval and interpolated between spike times to generate a continuous firing rate trace (Carey and Wachowiak 2011). These traces were then averaged across all model or experimental units.…”

“…Output from the OB via mitral/tufted cells (MCs) is also transient and linked to inhalation but is distinct from the simple excitatory bursts of ORN input, with MCs showing odorant-and cell-specific sequences of excitation and inhibition (Carey and Wachowiak 2011;Cury and Uchida 2010;Shusterman et al 2011). At the population level, odorant-evoked excitatory responses of MCs show a shorter duration and shorter rise time than do those of ORNs (Carey and Wachowiak 2011). This "temporal sharpening" of respiration-linked excitation is a key feature of the input-output transformation performed by the OB network.…”

“…Using biophysically-based models of major OB circuit elements, we asked what are the minimal circuits necessary to transform inhalation-driven packets of sensory input into temporally-sharpened bursts of MC output. Model simulation and evaluation were highly integrated with experimental data: we used dynamic input patterns derived from recordings of ORN population responses during naturalistic odorant sampling (i.e., sniffing), then used single-unit recordings from MC responses evoked by the same naturalistic odorant sniffs to evaluate the accuracy of model output (Carey and Wachowiak 2011). This approach identified several features of glomerular circuits that shape MC spiking responses with realistic inhalation-coupled temporal structure, including slow-onset and slowly-decaying inhibition and parallel feedforward excitation via ORNs and ET cells.…”