The smell of fear: innate threat of 2,5-dihydro-2,4,5-trimethylthiazoline, a single molecule component of a predator odor.

Jeffrey B Rosen,Arun Asok,Trisha Chakraborty

doi:10.3389/fnins.2015.00292

Abstract

In the last several years, the importance of understanding what innate threat and fear is, in addition to learning of threat and fear, has become evident. Odors from predators are ecologically relevant stimuli used by prey animals as warnings for the presence of danger. Of importance, these odors are not necessarily noxious or painful, but they have innate threat-like properties. This review summarizes the progress made on the behavioral and neuroanatomical fundamentals of innate fear of the predator odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a component of fox feces. TMT is one of several single molecule components of predator odors that have been isolated in the last several years. Isolation of these single molecules has allowed for rapid advances in delineating the behavioral constraints and selective neuroanatomical pathways of predator odor induced fear. In naïve mice and rats, TMT induces a number of fear and defensive behaviors, including robust freezing, indicating it is an innate threat stimulus. However, there are a number of behavioral constraints that we do not yet understand. Similarly, while some of the early olfactory sensory pathways for TMT-induced fear are being delineated, the pathways from olfactory systems to emotional and motor output regions are less well understood. This review will focus on what we know and what we still need to learn about the behavior and neuroanatomy of TMT-induced fear.

Highlights

In the last several years, the importance of understanding what innate threat and fear is, in addition to learning of threat and fear, has become evident
This review summarizes the progress made on the behavioral and neuroanatomical fundamentals of innate fear of the predator odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a component of fox feces
Isolation of these single molecules has allowed for rapid advances in delineating the behavioral constraints and selective neuroanatomical pathways of predator odor induced fear

Summary

TMT as an Unconditioned Fear Stimulus in Rodents

TMT is a synthetic compound that was originally isolated from fox feces by Vernet-Maury in the 1980s (Vernet-Maury et al., 1984). The studies just reviewed suggest that TMT’s fear inducing qualities are transmitted to the brain via two olfactory systems, there is the possibility that the noxious property of TMT is transduced through the trigeminal nerve to drive the freezing, avoidance, and other behavioral effects of TMT (McGregor et al, 2002; Fendt and Endres, 2008; Galliot et al, 2012) To address this issue, our lab recently demonstrated that olfactory bulb ablation completely blocked the freezing response to TMT, whereas transection of the infraorbital and ethmoidal branches of the trigeminal nerve (eliminating noxious sensations from the nasal cavity, mouth region, and whiskers) had no effect of TMT-induced freezing (Ayers et al, 2013). An interesting article on social aggregation of rats as a defense against prey, demonstrated that rats with a more active response to cat fur odor displayed less c-fos activation in the lateral septum suggesting that the septum may be involved in defensive aggregation (Bowen et al, 2013)

Conditioning Neuroanatomical Pathway

What We Still Need to Learn about the Behavior

Conclusions

Author Contributions