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

Mechanosensitive cells are essential for organisms to sense the external and internal environments, and a variety of molecules have been implicated as mechanical sensors. Here we report that odorant receptors (ORs), a large family of G protein-coupled receptors, underlie the responses to both chemical and mechanical stimuli in mouse olfactory sensory neurons (OSNs). Genetic ablation of key signaling proteins in odor transduction or disruption of OR-G protein coupling eliminates mechanical responses. Curiously, OSNs expressing different OR types display significantly different responses to mechanical stimuli. Genetic swap of putatively mechanosensitive ORs abolishes or reduces mechanical responses of OSNs. Furthermore, ectopic expression of an OR restores mechanosensitivity in loss-of-function OSNs. Lastly, heterologous expression of an OR confers mechanosensitivity to its host cells. These results indicate that certain ORs are both necessary and sufficient to cause mechanical responses, revealing a previously unidentified mechanism for mechanotransduction.

Insulin modulates network activity in olfactory bulb slices: impact on odour processing.

Odour perception depends closely on nutritional status, in animals as in humans. Insulin, the principal anorectic hormone, appears to be one of the major candidates for ensuring the link between olfactory abilities and nutritional status, by modifying processing in the olfactory bulb (OB), one of its main central targets. The present study investigates whether and how insulin can act in OB, by evaluating its action on the main output neurons activities, mitral cells (MCs), in acute rat OB slices. Insulin was found to act at two OB network levels: (1) on MCs, by increasing their excitability, probably by inhibiting two voltage-gated potassium (K(+)) channels; (2) on interneurons by modifying the GABAergic and on glutamatergic synaptic activity impinging on MCs, mainly reducing them. Insulin also altered the olfactory nerve (ON)-evoked excitatory postsynaptic currents in 60% of MCs. Insulin decreased or increased the ON-evoked responses in equal proportion and the direction of its effect depended on the initial neuron ON-evoked firing rate. Indeed, insulin tended to decrease the high and to increase the low ON-evoked firing rates, thereby reducing inter-MC response firing variability. Therefore, the effects of insulin on the evoked firing rates were not carried out indiscriminately in the MC population. By constructing a mathematical model, the impact of insulin complex effects on OB was assessed at the population activity level. The model shows that the reduction of variability across cells could affect MC detection and discrimination abilities, mainly by decreasing and, less frequently, increasing them, depending on odour quality. Thus, as previously proposed, this differential action of insulin on MCs across odours would allow this hormone to put the olfactory function under feeding signal control, given the discerning valence of an odour as a function of nutritional status.

Spontaneous and sensory-evoked activity in mouse olfactory sensory neurons with defined odorant receptors.

Sensory systems need to tease out stimulation-evoked activity against a noisy background. In the olfactory system, the odor response profile of an olfactory sensory neuron (OSN) is dependent on the type of odorant receptor it expresses. OSNs also exhibit spontaneous activity, which plays a role in establishing proper synaptic connections and may also increase the sensitivity of the cells. However, where the spontaneous activity originates and whether it informs sensory-evoked activity remain unclear. We addressed these questions by examining patch-clamp recordings of genetically labeled mouse OSNs with defined odorant receptors in intact olfactory epithelia. We show that OSNs expressing different odorant receptors had significantly different rates of basal activity. Additionally, OSNs expressing an inactive mutant I7 receptor completely lacked spontaneous activity, despite being able to fire action potentials in response to current injection. This finding strongly suggests that the spontaneous firing of an OSN originates from the spontaneous activation of its G protein-coupled odorant receptor. Moreover, OSNs expressing the same receptor displayed considerable variation in their spontaneous activity, and the variation was broadened upon odor stimulation. Interestingly, there is no significant correlation between the spontaneous and sensory-evoked activity in these neurons. This study reveals that the odorant receptor type determines the spontaneous firing rate of OSNs, but the basal activity does not correlate with the activity induced by near-saturated odor stimulation. The implications of these findings on olfactory information processing are discussed.

Odor information processing by the olfactory bulb analyzed in gene-targeted mice.

In mammals, olfactory sensory neurons (OSNs) expressing a specific odorant receptor (OR) gene project with precise stereotypy onto mitral/tufted (M/T) cells in the main olfactory bulb (MOB). It remains challenging to understand how incoming olfactory signals are transformed into outputs of M/T cells. By recording from OSNs expressing mouse I7 receptor and their postsynaptic neurons in the bulb, we found that I7 OSNs and their corresponding M/T cells exhibit similarly selective tuning profiles at low concentrations. Increasing the concentration significantly reduces response selectivity for both OSNs and M/T cells, although the tuning curve of M/T cells remains comparatively narrow. By contrast, interneurons in the MOB are broadly tuned, and blocking GABAergic neurotransmission reduces selectivity of M/T cells at high odorant concentrations. Our results indicate that olfactory information carried by an OR is channeled to its corresponding M/T cells and support the role of lateral inhibition via interneurons in sharpening the tuning of M/T cells.

Modulation of spontaneous and odorant-evoked activity of rat olfactory sensory neurons by two anorectic peptides, insulin and leptin.

In mammals, the sense of smell is modulated by the status of satiety, which is mainly signaled by blood-circulating peptide hormones. However, the underlying mechanisms linking olfaction and food intake are poorly understood. Here we investigated the effects of two anorectic peptides, insulin and leptin, on the functional properties of olfactory sensory neurons (OSNs). Using patch-clamp recordings, we analyzed the spontaneous activity of rat OSNs in an in vitro intact epithelium preparation. Bath perfusion of insulin and leptin significantly increased the spontaneous firing frequency in 91.7% (n = 24) and 75.0% (n = 24) of the cells, respectively. When the activity was electrically evoked, both peptides shortened the latency to the first action potential by approximately 25% and decreased the interspike intervals by approximately 13%. While insulin and leptin enhanced the electrical excitability of OSNs in the absence of odorants, they surprisingly reduced the odorant-induced activity in the olfactory epithelium. Insulin and leptin decreased the peak amplitudes of isoamyl acetate-induced electroolfactogram (EOG) signals to 46 and 38%, respectively. When measured in individual cells by patch-clamp recordings, insulin and leptin decreased odorant-induced transduction currents and receptor potentials. Therefore by increasing the spontaneous activity but reducing the odorant-induced activity of OSNs, an elevated insulin and leptin level (such as after a meal) may result in a decreased global signal-to-noise ratio in the olfactory epithelium, which matches the smell ability to the satiety status.