Combinatorial effects of odorants on mouse behavior

Abstract

The mechanisms by which odors induce instinctive behaviors are largely unknown. Odor detection in the mouse nose is mediated by >1, 000 different odorant receptors (ORs) and trace amine-associated receptors (TAARs). Odor perceptions are encoded combinatorially by ORs and can be altered by slight changes in the combination of activated receptors. However, the stereotyped nature of instinctive odor responses suggests the involvement of specific receptors and genetically programmed neural circuits relatively immune to extraneous odor stimuli and receptor inputs. Here, we report that, contrary to expectation, innate odor-induced behaviors can be context-dependent. First, different ligands for a given TAAR can vary in behavioral effect. Second, when combined, some attractive and aversive odorants neutralize one another's behavioral effects. Both a TAAR ligand and a common odorant block aversion to a predator odor, indicating that this ability is not unique to TAARs and can extend to an aversive response of potential importance to survival. In vitro testing of single receptors with binary odorant mixtures indicates that behavioral blocking can occur without receptor antagonism in the nose. Moreover, genetic ablation of a single receptor prevents its cognate ligand from blocking predator odor aversion, indicating that the blocking requires sensory input from the receptor. Together, these findings indicate that innate odor-induced behaviors can depend on context, that signals from a single receptor can block innate odor aversion, and that instinctive behavioral responses to odors can be modulated by interactions in the brain among signals derived from different receptors.olfaction | behavior | TAAR | odorants

Trace Amines and Their Receptors

“…Thus far, such agonists have been identified for one human, one macaque, six mouse, three rat, and 12 zebrafish TAARs (Table 2 and Table 9) (Liberles and Buck, 2006;Ferrero et al, 2012;Wallrabenstein et al, 2013;Horowitz et al, 2014;Liberles, 2015;Saraiva et al, 2016). In many of these cases, however, further investigation of receptor and species specificity, as well as the physiologic functions mediated by receptor activation, is required to fully validate the identified chemical cues as the true ligands of individual TAAR (Liberles, 2015).…”

“…Recent comprehensive screening for olfactory TAAR ligands and analysis of their attractive and avoidance properties in mice has revealed a complex organization of TAAR-mediated innate behavioral effects. These innate behavioral responses are not only both context and concentration dependent, but they are also subject to modification by other odorants (Saraiva et al, 2016). Thus, it is likely that TAAR-mediated hard-wired behavioral responses to socially relevant odorant cues are further modulated in brain circuitry due to interactions with signals derived from other odorant receptors or environmental cues.…”

“…Potent ligands for TAAR2 are yet to be identified, although several compounds that can activate this receptor at high concentrations were recently reported (Saraiva et al, 2016).…”

“…The archetypal diamine cadaverine is a major component of rotting flesh that potently activates zebrafish TAAR13c present in olfactory sensory neurons that Saraiva et al (2016). c Liberles and Buck (2006).…”

“…3) and these compounds are often associated with metabolic routes that are distinct from those of the compounds traditionally called trace amines. Such compounds include the endogenous thyroid hormone metabolite 3-iodothyronamine (3IT) (Scanlan et al, 2004;Dinter et al, 2015c), the catecholamine neurotransmitter metabolites 3-methoxytyramine (3-MT) and normetanephrine (Bunzow et al, 2001;Sotnikova et al, 2010), trimethylamine (Ferrero et al, 2012;Wallrabenstein et al, 2013;Li et al, 2015), isoamylamine (Liberles and Buck, 2006;Ferrero et al, 2012), the polyamines putrescine and cadaverine (Hussain et al, 2013), and possibly agmatine, spermine, and spermidine (Saraiva et al, 2016). In addition, the N-methylated metabolites of both PEA and TYR, Nmethylphenylethylamine and N-methyltyramine, are also TAAR agonists , as is the N-methyl metabolite of TRP N,N-dimethyltryptamine (DMT); although in this latter instance, this shows a strong species dependence (Simmler et al, 2016).…”