In contrast, weakly sorbed odorants—for example the terpene d-limonene, a principal component of orange odor—absorb slowly onto the epithelium and so tend to remain in the air stream as inhaled odorant passes through the nasal cavity. For these compounds, increasing flow rate will have little effect on odorant deposition. Thus, responses to a strongly-sorbed odorant should increase as flow rate increases, while responses to a weakly sorbed odorant should remain constant or even decrease (Hahn et al., 1994). Such effects have been measured at the level of the olfactory epithelium in reduced rodent preparations (Kent et al., 1996 and Scott-Johnson et al., 2000) and,

recently, in the OB using artificial inhalation (Oka et al.,

2009). The sorption hypothesis remains untested during natural odor sampling, however, with earlier studies relying primarily on steady-state flow rates, selleck chemicals not the transient changes in flow that occur during natural respiration and active sniffing. Thus, whether animals modulate sniff flow rate in order to actively modulate odorant response patterns remains unclear. A second way in which sniffing behavior can alter ORN response patterns is through changes in sniff frequency. High-frequency (6–10 Hz) sniff bouts lasting up to several seconds are one of the most distinctive odor sampling strategies in mammals, particularly during exploratory behavior (Macrides, 1975 and Welker, 1964). High-frequency sniffing shapes ORN responses in unexpected ways. An intuitive prediction GSK1349572 in vitro is that increases in sniff frequency lead to increased ORN responses—and perhaps recruitment of activation of new

ORN populations—due to an increased odorant influx. This prediction however has been tested using presynaptic calcium imaging from ORN axon terminals in the OB of awake rats, which sampled the same odorant during low frequency (1–2 Hz) respiration or during high-frequency (4–8 Hz) exploratory sniffing (Verhagen et al., 2007). Surprisingly, sampling an odorant at high-frequency only weakly enhanced the initial response to the odorant and did not recruit activation of new ORN populations. More importantly, sustained high-frequency sniffing of odorant led to a strong attenuation of ORN response magnitude ( Figure 4A). Sniff frequency-dependent attenuation is rapidly reversible, with ORN response magnitudes recovering within one second after sniffing returns to below 4 Hz. A likely cellular mechanism mediating the frequency-dependent attenuation of ORN inputs to the OB is simple adaptation. At low respiration rates, ORNs can recover from adaptation in the interval between successive inhalations, but higher sniff frequencies allow less time for recovery between cycles ( Reisert and Matthews, 2001).