Sniff Olfactometry: Temporal effects on odorant mixture perception in humans

10.26434/chemrxiv.10293395 ◽

2019 ◽

Author(s):

Kaifeng Ding ◽

Xiaoyuan Wang ◽

Dmitry Rinberg ◽

Terry Acree

Keyword(s):

Olfactory Bulb ◽

Linear Function ◽

Binary Mixtures ◽

Temporal Resolution ◽

Olfactory Epithelium ◽

Temporal Structure ◽

Odor Perception ◽

Temporal Effects ◽

Recognition Probability ◽

Human Odor

There is evidence in mice and honeybees that signals initiated by odorants at the olfactory epithelium arrive downstream in the olfactory bulb between 10 and 200ms later and that these latencies are ligand dependent. It has recently been proposed that these latencies could be used by mice to identify or classify. Here we demonstrate that humans are sensitive to the timing of individual of odorant presentation. Using a two-alternate forced choice (2AFC) paradigm—subjects chose which odorant they recognized first after they experienced two 70ms puffs separated in time by some interval in the range of -450ms to +450ms. All subject recognition probabilities yielded the same linear function of latency (p<0.05) even though they differed in their recognition thresholds for the components and their recognition probability to detect them in binary mixtures. These results indicate that temporal structure of odor delivery affects human odor perception and sniff olfactometry (SO) has the temporal resolution necessary to measure these effects. <div><br></div>

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Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

10.1101/2020.03.25.009084 ◽

2020 ◽

Cited By ~ 65

Author(s):

David H. Brann ◽

Tatsuya Tsukahara ◽

Caleb Weinreb ◽

Marcela Lipovsek ◽

Koen Van den Berge ◽

...

Keyword(s):

Olfactory Bulb ◽

Olfactory Epithelium ◽

Neuronal Cell ◽

Cell Types ◽

Cell Entry ◽

Common Symptom ◽

Supporting Cells ◽

Odor Perception ◽

Human Olfactory Mucosa ◽

Human Primate

AbstractAltered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing revealed that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing and immunostaining demonstrated ACE2 expression in support cells, stem cells, and perivascular cells; in contrast, neurons in both the olfactory epithelium and bulb did not express ACE2 message or protein. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

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Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1505068112 ◽

2015 ◽

Vol 112 (41) ◽

pp. 12846-12851 ◽

Cited By ~ 24

Author(s):

Filomene G. Morrison ◽

Brian G. Dias ◽

Kerry J. Ressler

Keyword(s):

Olfactory Bulb ◽

Learning And Memory ◽

Olfactory Epithelium ◽

Olfactory System ◽

Structural Changes ◽

Freezing Behavior ◽

Extinction Training ◽

Odor Stimulus ◽

Main Olfactory Epithelium ◽

Odor Learning

Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learning-induced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.

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Water response of the frog olfactory epithelium as observed from the olfactory bulb.

The Journal of Physiology ◽

10.1113/jphysiol.1978.sp012364 ◽

1978 ◽

Vol 279 (1) ◽

pp. 605-619 ◽

Cited By ~ 5

Author(s):

H Arito ◽

M Iino ◽

S F Takagi

Keyword(s):

Olfactory Bulb ◽

Olfactory Epithelium ◽

Water Response

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Nonlinear effects of noradrenergic modulation of olfactory bulb function in adult rodents

Journal of Neurophysiology ◽

10.1152/jn.00960.2010 ◽

2011 ◽

Vol 105 (4) ◽

pp. 1432-1443 ◽

Cited By ~ 42

Author(s):

Christiane Linster ◽

Qiang Nai ◽

Matthew Ennis

Keyword(s):

Olfactory Bulb ◽

Nonlinear Effects ◽

Main Olfactory Bulb ◽

Odor Perception ◽

Different Types ◽

Species Specific ◽

Odor Preferences ◽

Noradrenergic Modulation ◽

Specific Odor

The mammalian main olfactory bulb receives a significant noradrenergic input from the locus coeruleus. Norepinephrine (NE) is involved in acquisition of conditioned odor preferences in neonatal animals, in some species-specific odor-dependent behaviors, and in adult odor perception. We provide a detailed review of the functional role of NE in adult rodent main olfactory bulb function. We include cellular, synaptic, network, and behavioral data and use computational simulations to tie these different types of data together.

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Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

Science Advances ◽

10.1126/sciadv.abc5801 ◽

2020 ◽

Vol 6 (31) ◽

pp. eabc5801 ◽

Cited By ~ 84

Author(s):

David H. Brann ◽

Tatsuya Tsukahara ◽

Caleb Weinreb ◽

Marcela Lipovsek ◽

Koen Van den Berge ◽

...

Keyword(s):

Olfactory Bulb ◽

Neuronal Cell ◽

Cell Types ◽

Cell Entry ◽

Common Symptom ◽

Supporting Cells ◽

Odor Perception ◽

Sustentacular Cells ◽

Human Olfactory Mucosa ◽

Human Primate

Abstract:Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

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Circuit Properties Generating Gamma Oscillations in a Network Model of the Olfactory Bulb

Journal of Neurophysiology ◽

10.1152/jn.01141.2005 ◽

2006 ◽

Vol 95 (4) ◽

pp. 2678-2691 ◽

Cited By ~ 71

Author(s):

Brice Bathellier ◽

Samuel Lagier ◽

Philippe Faure ◽

Pierre-Marie Lledo

Keyword(s):

Olfactory Bulb ◽

Firing Rate ◽

Lateral Inhibition ◽

Temporal Structure ◽

Gamma Oscillations ◽

Synaptic Organization ◽

Neural Basis ◽

Sensory Inputs ◽

Model Based

The study of the neural basis of olfaction is important both for understanding the sense of smell and for understanding the mechanisms of neural computation. In the olfactory bulb (OB), the spatial patterning of both sensory inputs and synaptic interactions is crucial for processing odor information, although this patterning alone is not sufficient. Recent studies have suggested that representations of odor may already be distributed and dynamic in the first olfactory relay. The growing evidence demonstrating a functional role for the temporal structure of bulbar neuronal activity supports this assumption. However, the detailed mechanisms underlying this temporal structure have never been thoroughly studied. Our study focused on gamma (40–100 Hz) network oscillations in the mammalian OB, which is a form of temporal patterning in bulbar activity elicited by olfactory stimuli. We used computational modeling combined with electrophysiological recordings to investigate the basic synaptic organization necessary and sufficient to generate sustained gamma rhythms. We found that features of gamma oscillations obtained in vitro were identical to those of a model based on lateral inhibition as the coupling modality (i.e., low irregular firing rate and high oscillation stability). In contrast, they differed substantially from those of a model based on lateral excitatory coupling (i.e., high regular firing rate and instable oscillations). Therefore we could precisely tune the oscillation frequency by changing the kinetics of inhibitory events supporting the lateral inhibition. Moreover, gradually decreasing GABAergic synaptic transmission decreased the degree of relay neuron synchronization in response to sensory inputs, both theoretically and experimentally. Thus we have shown that lateral inhibition provides a mechanism by which the dynamic processing of odor information might be finely tuned within the OB circuit.

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