Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors

“The SO was recently shown to respond to multiple volatile odorants that are also detected by the main olfactory epithelium (Grosmaitre et al., 2007; Ma et al., 2003).”

“This is evident in clean-air sniff-induced activity at the olfactory epithelium (Grosmaitre et al. 2007), bulb (Adrian 1942), and cortex (Sobel et al. 1998, Zelano et al. 2005).”

“Of note, while neuronal activity locked to sensory afferents depends on nasal airflow, the stimulating air need not contain odorants [51].”

“Importantly, several of these areas are activated during sniffing in the absence of odorant, presumably by the airflow-driven, somatosensory component of a sniff (Adrian, 1942; Sobel et al., 1998a; Grosmaitre et al., 2007).”

“The mechanical sensitivity of OSNs is also observed in the MOE and has been hypothesized to serve at least two functions: (a) to modulate sensory responses of OSNs with respect to airflow and (b) to synchronize rhythmic activity in the olfactory bulb with respiration (153).”

“To assess timing of the respiratory cycle, a pressure sensor mounted in a nasal cannula can measure nasopharyngeal airflow (Zelano et al., 2016), indexing activation of mechano-sensitive olfactory sensory neurons (Grosmaitre, Santarelli, Tan, Luo, & Ma, 2007).”

“In some OSNs, activity is modulated by the sniff cycle in the absence of overt odour stimulation, perhaps responding to airflow or background odou”

“This sniV-driven activity may partly reXect an often-overlooked property of olfactory receptors, namely their possible dual-function as mechanoreceptors that sense air Xow (Adrian 1942; Grosmaitre et al. 2007).”

“Further studies suggested that the relevant stimulus for slow OB oscillations is nasal airflow rather than specific odor stimuli: indeed, olfactory sensory neurons do react to mechanical stimulation by odorless airflow (Grosmaitre et al., 2007).”

“(legend continued on next page) 1222 Neuron 80, 1218–1231, December 4, 2013 ª2013 Elsevier Inc. to the mechanosensory properties of olfactory sensory neurons (Grosmaitre et al., 2007).”

“07, n= 8, paired two-tailed Student’s t test t(7)= 5.”

“Because control stimuli (pure air or air from the mineral oil) occasionally elicited weak responses from some cells (Grosmaitre et al., 2007), we further subtracted the value of response strength to controls from that of the cell to odorants.”

“In turn, the resulting rhythmic airflow through the nasal cavity activates olfactory sensory neurons (Grosmaitre et al., 2007; Verhagen et al., 2007) and imposes a reafferent periodicity in downstream olfactory areas (Adrian, 1942).”

“, 2003) or be uncoupled from respirations (Grosmaitre et al., 2007).”

“CNGA2 is implicated in olfactory functioning (Grosmaitre et al. 2007) which, given the assumed importance of pheromonal cues for Pacific lamprey (e.g. Yun et al. 2011), may help explain the predictive power of latitude for variation at this locus.”

“These feedback signals not only encode odour information in olfactory receptor cells [37], but also mechanical stimulation of mechanoreceptors triggered by nasal airflow [38].”

“Additional, smaller sensory structures include a group of neurons at the tip of the nose, the Grueneberg ganglion, which is thought to detect alarm pheromones and structurally related predator odorants [100,101], and a patch of olfactory neurons on the nasal septum that largely express a single broadly-tuned OR andmay…”

“In the olfactory system, the respiratory rhythmicity is predominantly imposed by the temporal variation in odor sampling and nasal mechanoreceptor activation ( 8 – 10 , 12 , 13 ).”

“Because MTCs show no inhalation-linked patterning in the absence of artificial inhalation and inhalation without odorant elicits weak sensory inputs to the OB (Grosmaitre et al., 2007; Carey et al., 2009), we interpret inhalation-linked MTC activity as reflecting weak sensory-evoked responses.”

“Even when there is no odor, mammalian olfactory sensory neurons detect the mechanical pressure caused by airflow in the nostril (Grosmaitre et al., 2007).”

“The activation of granule cells within bilaterally symmetric regions in contralateral MOB strongly suggested odorant-driven activation of contralateral granule cells instead of nonselective activation by enhanced mechanosensory input following naris occlusion (Grosmaitre et al., 2007).”

“and recordings in (B) and (C) are taken from (Grosmaitre et al., 2007).”

“Such a process may be mediated by mechanosensitivity of olfactory cilia [48].”

“Both in wild-type mice and in gene-targeted mice, there is a close correlation between broad responsiveness and mechanosensitivity (Grosmaitre et al., 2007).”

“The OSNs appear to respond to both odorant binding at the receptors and mechanical stimulation (Grosmaitre et al., 2007), which in turn sends a volley of activity through the olfactory nerve that reaches the OB.”

“We recently discovered that a subset of mouse OSNs exhibited responses to both odor and mechanical force, but these responses were absent in OSNs from CNG channel knockout mice (4).”

“Stimulation of ORNs in the mucosa by odorants or airflow (Grosmaitre et al. 2007) generates action potentials that travel along the olfactory nerve and arrive at glomeruli, releasing glutamate and depolarizing the apical dendrites of M/T cells.”

“This not only yields coordinated patterns of behavior, but also coordinated activity in associated neural circuits (Kay, 2005; Grosmaitre et al., 2007; Cury and Uchida, 2010; Shusterman et al., 2011; Deschênes et al., 2012; Miura et al., 2012; Moore et al., 2013).”

“A single dose–response curve is then fit based on the data from all neurons within each age group, using a modified Hill equation, Inorm (I Ibaseline)/Imax 1/(1 (K1/2/C) , where I represents the peak current, Ibaseline the nonzero mechanical response induced by a Ringer puff (Grosmaitre et al., 2007), Imax the maximum…”

“2) There is odorant-independent activation, for example a mechanosensitive-OSN response to changes in flow [45] (unlikely as the cells didn’t respond to a pulse of DMSO).”

“Nasal airflow is hypothesized to activate mechanical receptors of ORNs and modulate patterns of excitatory synaptic inputs to OB glomeruli (Spors and Grinvald, 2002; Grosmaitre et al., 2007; Carey et al., 2009; Oka et al., 2009).”

“Inhalation alone evokes weak OSN inputs to the OB (Grosmaitre et al., 2007; Carey et al., 2009), which are presumably relayed to the AON and which may, as our recordings suggest, trigger inhalation-coupled AON feedback even in the absence of odorant.”

“Distance and pressure were adjusted to minimize mechanical responses (Grosmaitre et al., 2007).”

“recently that they do not only respond to odorants but also to mechanical stimuli (Grosmaitre et al., 2007).”

“Also, accumulating evidence shows that many OSNs robustly respond to mechanical stimuli produced by the nasal airflow (Chen et al., 2012; Connelly et al., 2015; Grosmaitre et al., 2007; Iwata et al., 2017).”

“…et al., 2009) or in vivo after tracheotomy (Ravel and Pager, 1990; Fontanini et al., 2003), pharmacological blockade of the sensory input (Stakic et al., 2011), or uncoupling from the respiratory cycle (Grosmaitre et al., 2007) suggests that slow rhythmic activity is also intrinsic to OB circuits.”

“Similar dual functioning neurons integrating chemical information with touch have been described in nematodes (Kaplan and Horvitz, 1993), mammalian olfactory receptors (Grosmaitre et al., 2007), and vertebrate nociceptor systems (Besson and Chaouch, 1987; Woolf and Walters, 1991).”

“The specific function of the septal organ has not been established; its neurons may also have mechanosensory abilities (Grosmaitre et al., 2007).”

“1B,D), presumably reflecting responses to weak activation of OSNs by inhalation alone (Grosmaitre et al., 2007; Carey et al., 2009).”

“However, because I7 neurons responded to odor-free Ringer solution puffs under this condition, we had to move the puffing pipette to ϳ70 ␮m away to eliminate the mechanical responses elicited by pressure ejection (Grosmaitre et al. 2007).”

“Is not deprivation in an impoverished environment of less moment than deprivation in an enriched environment? Considering these facts it is interesting that OSNs, in addition to responding to odor ligands, are exquisite mechanoreceptors [90].”

“Recent work suggests that the septal organ is both broadly tuned to various volatile odors and also shows a unique sensitivity to mechanical stimulation [38].”

“In addition, in the frequency, the LFP partially follows sniffing (Grosmaitre et al., 2007; Rosero and Aylwin, 2011; Gschwend et al., 2012; Khan et al., 2012), and sniffing has been postulated to provide a temporal basis to extract odor identity (Cury and Uchida, 2010; Shusterman et al.”

“The most intriguing explanation is that GGNs may act as multimodal sensors that are responsive to both thermo- and chemostimuli, thus joining an only recently discovered group of mammalian olfactory neurons with dual or multiple functions (Grosmaitre et al., 2007; Zufall and Munger, 2010).”

“On the basis of its broad spectrum for odor detection (Marshall and Maruniak 1986 ), the pronounced mechanosensitivity of its ORNs (Grosmaitre et al. 2007) and its distinct projection pattern to the ventral olfactory bulb (Levai and Strotmann 2003), the SO has been suggested to raise alertness to…”

“Recent in vitro electrophysiological study has shown that OSNs have the ability to respond to mechanical stimulation, suggesting that mechanical and odorant responses may be integrated in the OSN (Grosmaitre et al., 2007).”

“Thus, a reduction in the number of mature OSNs would result in less glutamatergic innervation of M/T cells, leading to reduced excitation and theta oscillations seen in the present study [52, 53], in addition to decreased EOG amplitude.”

“For example, Masera’s organ, which expresses only a fraction of the OR repertoire (Kaluza et al. 2004; Tian and Ma 2004), is extremely sensitive to a wide variety of odorant stimuli (Grosmaitre et al. 2007; Marshall and Maruniak 1986).”

“These observations make sense, since OB -cycles result from air movements on the olfactory epithelium, at the back of the nasal cavity (Grosmaitre et al. 2007).”

“In the absence of odor stimulation, 27% (119 of 440 cells recorded) of AON neurons showed respiration phase-locked spike discharges which were presumably induced by room air odorants or periodic mechanical stimulation of the olfactory sensory neurons resulting from nasal airflow (Grosmaitre et al., 2007).”

“A subset of OSNs in the mouse olfactory epithelium can respond to mechanical stimulation in addition to odors [45].”

“These data are consistent with other no-odor or “sniff-related” activity that has been observed at (1) the olfactory epithelium [Grosmaitre et al., 2007]; (2) the bulb [Adrian, 1942]; and (3) the cortex [Sobel et al., 1998a,b; Zelano and Sobel, 2005].”

“It is worth noticing that this drive is also provided by the mechanical stimulation through nasal air movement, even in the absence of odors (Grosmaitre et al., 2007; Connelly et al., 2015).”

“For these cells, it has been proposed that an increased airflow in the nose during sniffing could mechanically sensitize these neurons for a chemical stimulus (Grosmaitre et al. 2007).”

“Patterned activity to air alone may be explained by recent work on mechanosensitive properties of ORNs (Grosmaitre et al., 2007).”

“In this case, the mechanical impact of the air in the nose upon each breath cycle is picked up by the olfactory sensory neurons (Grosmaitre et al. 2007), which results in the neural OB’s respiratory rhythm.”

“To do so, we used UNO, a procedure that provides a simple method for reproducibly reducing olfactory stimulation (broadly defined here as both odor- and mechanically derived; Grosmaitre et al., 2007) on the closed side of the OE, as well as a within-animal control (the open side of the OE).”

“As anticipated in the Introduction, the aim of the study was that of driving brain electrical activity and modulating consciousness by delivering rhythmic pressurized-air stimulations to the olfactory epithelium, whose receptors have been shown to be sensitive also to mechanical stimuli 4 .”

“Indeed, these neurons respond not only to odorant binding but also to mechanical (pressure) stimuli 182 , with both mechanosensitivity and chemosensitivity being mediated by the same membrane receptors 182,183 .”