Author:

Abstract:

Food source localization, danger avoidance, and navigation critically depend on the identification and spatial localization of airborne chemicals. When monitoring the olfactory environment, rodents spontaneously orient their sensory organs and engage in active olfactory sampling behavior, also referred to as orienting reflex (Welker, 1964). Olfactory orienting is characterized by two orofacial behaviors, a stereotypical high-frequency respiration and nose movements which are also reliably evoked by novel odorant stimuli (Wesson, Carey, et al., 2008; Wesson, Donahou, et al., 2008). To study novelty-induced olfactory orienting, we developed a novel, non-contact method for measuring respiration frequency by infrared (IR) thermography in a behavioral paradigm, in which we present novel and familiar stimuli to awake and head-restrained mice. We validated the method by simultaneously performing nasal pressure measurements, a commonly used invasive approach (Reisert et al., 2014; Wesson, Donahou, et al., 2008), and confirmed the highly reliable detection of inhalation onsets. I further discovered that mice actively orient their nostrils towards novel, previously unexperienced, smells. In line with the remarkable speed of olfactory processing reported previously (Resulaj & Rinberg, 2015; Uchida et al., 2006; Wesson, Carey, et al., 2008), I found that mice initiate their orienting response within the first sniff after odor onset. Moreover, by transecting the anterior commissure (AC), I disrupted the nasal orienting response, indicating that it requires an interhemispheric transfer of information and suggests mice compare odorant information obtained from the two bilaterally symmetric nostrils to locate the source of the novel odorant. I further demonstrated that asymmetric activation of the anterior olfactory nucleus (AON) is both necessary and sufficient for eliciting orienting responses. These findings support the view that the AON plays an essential role in the internostril difference comparison underlying rapid odor source localization. I performed viral circuit tracing techniques of the AON projections to shed light on the long-range AON connectivity to the rest of the brain, focusing on the areas controlling orienting behaviors. I described previously unknown AON projections to midbrain and brainstem areas and confirmed the AON projects to selected targets previously involved in orienting behaviors. Finally, I optogenetically stimulated an AON circuit related to breathing changes, and proved the existence of an AON-KF-preBötzinger circuit. In summary, the results showed that the AON is a fundamental olfactory structure involved in the neural circuit(s) responsible for rapid olfactory orienting to novel smells, opening new avenues of research to study AON function and connectivity.