Dynamics of Glutamatergic Drive Underlie Diverse Responses of Olfactory Bulb OutputsIn Vivo

Abstract

Mitral/tufted (MT) cells of the olfactory bulb (OB) show diverse temporal responses to odorant stimulation that are thought to encode odor information. Much of this diversity is thought to arise from inhibitory OB circuits, but the dynamics of excitatory input to MT cells, which is driven in a feedforward manner by sensory afferents, may also be important. To examine the contribution of excitatory input dynamics to generating temporal diversity in MT cells, we imaged glutamate signaling onto MT cell dendrites in anesthetized and awake mice. We found surprising diversity in the temporal dynamics of these signals. Inhalation-linked glutamate transients were variable in onset latency and duration, and in awake mice the degree of coupling to inhalation varied substantially with odorant identity and concentration. Successive inhalations of odorant produced nonlinear changes in glutamate signaling that included facilitating, adapting and suppressive responses and which varied with odorant identity and concentration. Dual-color imaging of glutamate and calcium signals from MT cells in the same glomerulus revealed highly correlated presynaptic and postsynaptic signals across these different response types. Suppressive calcium responses in MT cells were nearly always accompanied by suppression in the glutamate signal, providing little evidence for MT cell suppression by lateral or feedforward inhibition. These results indicate a high degree of diversity in the dynamics of excitatory input to MT cells, and suggest that these dynamics may account for much of the diversity in MT cell responses that underlies OB odor representations.

The Mammalian Olfactory Bulb Contributes to the Adaptation of Odor Responses: A Second Perceptual Computation Carried Out by the Bulb

“…Clearly, olfactory receptor neurons exhibit synaptic depression under some conditions, which would be transmitted to the mitral/tufted cells. The relative proportion of mitral/tufted cell adaptation that can be attributed to depression at the olfactory receptor neuron synapse needs to be addressed in future work using either sensors of synaptic vesicle release ( Bozza et al, 2004 ; Wachowiak et al, 2005 ) or glutamate targeted to postsynaptic neurons ( Marvin et al, 2013 , 2018 ; Moran et al, 2021 ).…”

Circuit contributions to sensory-driven glutamatergic drive of olfactory bulb mitral and tufted cells during odorant inhalation

“…The copyright holder for this preprint this version posted September 17, 2021. ; https://doi.org/10.1101/2021.09.15.460561 doi: bioRxiv preprint significant change in onset or peak latency (see Fig. 1G legend), the magnitude of the change in these experiments (<10 ms) was negligible compared to the range of onset and peak latencies seen across different glomeruli in the same preparation, which ranges over a span of 200 -250 ms (Moran et al, 2021). These results confirm that GABAB-mediated inhibition regulates the strength of glutamatergic signaling from presynaptic sources onto MT cells in vivo (McGann et al, 2005;Wachowiak et al, 2005;Brunert et al, 2016), and suggest that presynaptic inhibition contributes little to the inhalation-linked timing of these signals.…”

“…Potential OB circuit mechanisms for shaping MT cell output dynamics have been well-characterized using OB slice preparations, and include modulation of glutamate release from ET cells onto MT cells (Hayar et al, 2004a;De Saint Jan et al, 2009;Gire et al, 2012) as well as feedforward inhibition via several distinct inhibitory interneuron pathways (Murphy et al, 2005;Gire and Schoppa, 2009;Shao et al, 2012). In a recent study using glutamate and Ca 2+ imaging from the mouse OB in vivo (Moran et al, 2021), we found that glutamatergic signaling onto MT cells showed complex dynamics both within and across inhalations and that the slower temporal patterning was well-correlated with that of MT cell Ca 2+ signals, highlighting the importance of excitatory pathways in generating MT cell patterning.…”

“…5A). This protocol yielded inhalation-triggered average waveforms that showed substantial variation in onset and peak latency as well as duration, as we have reported previously (Short and Wachowiak, 2019;Moran et al, 2021). Finally, in a subset of mice (n = 2), we used dualcolor imaging to simultaneously image presynaptic glutamate transients and postsynaptic Ca 2+ signals in the apical glomerular tufts of overlapping MT cell populations (Fig.…”

“…Finally, we sought to further examine the role of direct versus multisynaptic excitation in shaping the dynamics of glutamatergic input to MT cells during repeated odorant sampling. We have shown previously that glutamate signals on MT cells show diverse temporal patterns across repeated inhalations of odorant that include adaptation, facilitation and even suppression depending on odorant identity and concentration (Moran et al, 2021). To capture this diversity, we used a 12-odorant panel (delivered concentrations ranging from 0.03 -15 ppm) and 3 Hz artificial inhalation, comparing response patterns before and after application of APV+NBQX (1 mM/0.5 mM).…”