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

Abstract

Most sensory systems are primarily specialized to detect one sensory modality. Here we report that olfactory sensory neurons (OSNs) in the mammalian nose can detect two distinct modalities transmitted by chemical and mechanical stimuli. As revealed by patch-clamp recordings, many OSNs respond not only to odorants, but also to mechanical stimuli delivered by pressure ejections of odorfree Ringer solution. The mechanical responses correlate directly with the pressure intensity and show several properties similar to those induced by odorants, including onset latency, reversal potential and adaptation to repeated stimulation. Blocking adenylyl cyclase or knocking out the cyclic nucleotide-gated channel CNGA2 eliminates the odorant and the mechanical responses, suggesting that both are mediated by a shared cAMP cascade. We further show that this mechanosensitivity enhances the firing frequency of individual neurons when they are weakly stimulated by odorants and most likely drives the rhythmic activity (theta oscillation) in the olfactory bulb to synchronize with respiration.Receptor cells within each sensory system are specialized to detect a certain modality (for example, vision, hearing, touch, taste or smell) and to convert external stimuli into intracellular signals. Odor detection via the olfactory system relies on a large family of odorant receptors expressed in the olfactory sensory neurons (OSNs) within the neuroepithelium of the nose 1 . These odorant receptors initiate a cAMP pathway that enables olfactory signal transduction 2 . Binding of odor molecules to odorant receptors sequentially activates a specific G protein (Golf) and adenylyl cyclase type III (ACIII), which increases the intracellular cAMP level. Later opening of specific cyclic nucleotide-gated (CNG) channels by cAMP depolarizes the sensory neurons and triggers action potentials, which then permits odor information to reach the olfactory bulb in the brain.In addition to processing the convergent odor inputs from numerous OSNs, the olfactory bulb shows rhythmic activity (theta-band oscillation) coupled with respiration even in the absence of odorants, suggesting that the bulb also receives airflow information 3-8 . The mechanism underlying the rhythmic activity is not fully understood, although both peripheral and centrifugal sources are implicated 6,9-12 . Nonetheless, air intake, especially in the form of Correspondence should be addressed to M.M. (minghong@mail.med.upenn.edu.). AUTHOR CONTRIBUTIONS X.G. performed the recordings in the septal organ, L.C.S. performed the recordings in the main olfactory epithelium, J.T. performed the recordings in the olfactory bulb, M.L. supervised the bulb recordings, and M.M. supervised the whole project and drafted the manuscript. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. We show that the mechanosensitivity enhances the neuronal activity of individual OSNs when they are weakly stimulated by odorants. Furthermore, the mechanosensitivity of the...

G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons

“…The higher excitability is presumably attributed to functional compensation for the loss of ACIII mediated activity in these cells. These results indicate that ACIII is required for mechanosensitivity in OSNs (11), consistent with the pharmacological evidence obtained by an adenylyl cyclase blocker (4).…”

“…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). To determine whether the odor transduction cascade underlies both chemical and mechanical sensitivity in OSNs, we tested whether ablating targets upstream of the CNG channel would also eliminate mechanical responses.…”

Grueneberg Ganglion Neurons Are Finely Tuned Cold Sensors

“…But how can they be reconciled with the results of Brechbühl et al (2008)? 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). The newly characterized cGMP pathway is likely to underlie GGN chemoresponsivity, a conjecture that remains to be tested.…”

ϒ Spike-Field Coherence in a Population of Olfactory Bulb Neurons Differentiates between Odors Irrespective of Associated Outcome

“…5 A, B). In addition, we also studied LFP (4 -12 Hz) because it is somewhat, but not always, related to sniffs (Kay, 2005;Grosmaitre et al, 2007;Khan et al, 2012;Manabe and Mori, 2013). Indeed Figure 5C shows examples of the relationship of sniffs and LFP, and Figure 5D shows that there was a strong coherence of the sniff and the LFP.…”

“…In mammals, ϒ LFP responses in the OB are thought to carry information on odor identity (Nusser et al, 2001;Beshel et al, 2007;Lepousez and Lledo, 2013;Kay, 2014). 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, 2011;Wa-chowiak, 2011;Blauvelt et al, 2013). Finally, neuronal oscillation related to the LFP has been implicated to underlie extraction of information on odor identity (Laurent, 2002;Brody and Hopfield, 2003).…”