A physicochemical model of odor sampling

Abstract

We present a general physicochemical sampling model for olfaction, based on established pharmacological laws, in which arbitrary combinations of odorant ligands and receptors can be generated and their individual and collective effects on odor representations and olfactory performance measured. Individual odor ligands exhibit receptor-specific affinities and efficacies; that is, they may bind strongly or weakly to a given receptor, and can act as strong agonists, weak agonists, partial agonists, or antagonists. Ligands interacting with common receptors compete with one another for dwell time; these competitive interactions appropriately simulate the degeneracy that fundamentally defines the capacities and limitations of odorant sampling. The outcome of these competing ligand-receptor interactions yields a pattern of receptor activation levels, thereafter mapped to glomerular presynaptic activation levels based on the convergence of sensory neuron axons. The metric of greatest interest is the mean discrimination sensitivity, a measure of how effectively the olfactory system at this level is able to recognize a small change in the physicochemical quality of a stimulus. This model presents several significant outcomes, both expected and surprising. First, adding additional receptors reliably improves the system’s discrimination sensitivity. Second, in contrast, adding additional ligands to an odor scene initially can improve discrimination sensitivity, but eventually will reduce it as the number of ligands increases. Third, the presence of antagonistic ligand-receptor interactions produced clear benefits for sensory system performance, generating higher absolute discrimination sensitivities and increasing the numbers of competing ligands that could be present before discrimination sensitivity began to be impaired. Finally, the model correctly reflects and explains the modest reduction in odor discrimination sensitivity exhibited by transgenic mice in which the specificity of glomerular targeting by primary olfactory neurons is partially disrupted.

Dynamics of spike time encoding in the olfactory bulb

“…Concentration increases, however, generally evoke monotonic increases in the activation levels of individual glomeruli (and also may progressively recruit some new, lower-affinity glomeruli). These increases will not be linearly proportional to one another across glomeruli, but to a substantial extent the ordinal ranking of glomerular activation levels should be preserved (Araneda, Kini, & Firestein, 2000; Gronowitz et al, 2021). Quality differences, in contrast, involve sharply different ordinal rankings of glomerular activation levels.…”

“…These limitations on our understanding persist in part because odorant stimuli are difficult to control. All odorants – even monomolecular odorants – bind to multiple types of primary odorant receptors with different affinities and efficacies (discussed in Gronowitz, Liu, Qiu, Yu, & Cleland, 2021), such that primary olfactory sensory neuron (OSN) activation profiles vary nonlinearly and sometimes non-monotonically with concentration. Moreover, the timing of odor stimulus delivery is imprecise, rendering it difficult to determine whether variations in fine-scale temporal response properties arise from internally regulated OB network dynamics or simply from the undercontrolled timing of odorant delivery to receptors.…”

Activity‐dependent formation of the topographic map and the critical period in the development of mammalian olfactory system

“…that divergent innervation of multiple glomeruli by the same type of axons did not compromise odor detection, discrimination, or associative learning (Qiu, Wu, Ma, Xu, et al, 2021). Discrimination is only affected under extremely challenging conditions, for example, with highly similar odor mixtures (Gronowitz et al, 2021). However, response to innately recognized odors is altered in these mice (Qiu, Wu, Ma, Xu, et al, 2021).…”

“…In one study, by leveraging the requirement of spontaneous activity in establishing the convergent axon innervation pattern, Qiu and colleagues used inducible expression of Kir2.1 to perturb the olfactory map and showed that divergent innervation of multiple glomeruli by the same type of axons did not compromise odor detection, discrimination, or associative learning (Qiu, Wu, Ma, Xu, et al, 2021). Discrimination is only affected under extremely challenging conditions, for example, with highly similar odor mixtures (Gronowitz et al, 2021). However, response to innately recognized odors is altered in these mice (Qiu, Wu, Ma, Xu, et al, 2021).…”

Molecular, Cellular, and Developmental Organization of the Mouse Vomeronasal Organ at Single Cell Resolution

“…The anatomical arrangement in the AOB has strong implications as to how species-specific cues are encoded and how the information is processed. In the MOB, when the convergent glomerular innervation is experimentally perturbed to become divergent, it does not affect detection or discrimination of odorants but diminishes behavioral responses to innately recognized odors 74,75 . Thus, stereotypic projection patterns provide a basis for genetically specified connections in the neural circuitry to enable innate behaviors.…”