Navigation, finding food sources, and avoiding danger critically depend on the identification
and spatial localization of airborne chemicals. When monitoring the olfactory environment,
rodents spontaneously engage in active olfactory sampling behavior, also referred
to as exploratory sniffing [1]. Exploratory sniffing is characterized by stereotypical
high-frequency respiration, which is also reliably evoked by novel odorant stimuli
[2, 3]. To study novelty-induced exploratory sniffing, we developed a novel, non-contact
method for measuring respiration by infrared (IR) thermography in a behavioral paradigm
in which novel and familiar stimuli are presented to head-restrained mice. We validated
the method by simultaneously performing nasal pressure measurements, a commonly used
invasive approach [2, 4], and confirmed highly reliable detection of inhalation onsets.
We further discovered that mice actively orient their nostrils toward novel, previously
unexperienced, smells. In line with the remarkable speed of olfactory processing reported
previously [3, 5, 6], we find that mice initiate their response already within the
first sniff after odor onset. Moreover, transecting the anterior commissure (AC) disrupted
orienting, indicating that the orienting response requires interhemispheric transfer
of information. This suggests that mice compare odorant information obtained from
the two bilaterally symmetric nostrils to locate the source of the novel odorant.
We further demonstrate 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 important role in the internostril difference
comparison underlying rapid odor source localization.