More than a rhythm of life: breathing as a binder of orofacial sensation

Kleinfeld, David; Deschênes, Martin; Wang, Fan; Moore, Jeffrey D.

doi:10.1038/nn.3693

Cited by 97 publications

(102 citation statements)

References 52 publications

(74 reference statements)

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“…Consistent with this notion, a subset of glomeruli and mitral/tufted cells (the projection neurons in the olfactory bulb) exhibits spontaneous activities coupled to respiration in the absence of odors (33,39,40). Because mitral/tufted cells project diffusely to cortical regions, OSNs may indirectly provide a driving force to synchronize the activity of these cortical regions with respiration and serve as a common clock that binds orofacial sensation (5,41). We also speculate that respiration-related rhythmic activity may play a role in higher brain functions beyond sensory perception.…”

Section: Discussionmentioning

confidence: 78%

“…(1)(2)(3), but our understanding of the mechanical sensors is still limited. We previously discovered that some OSNs in the mammalian nose responded to mechanical stimulation (4), a feature that may allow the nose to carry an afferent signal of breathing to the brain and facilitate binding of orofacial sensation (5). In the current study, we aim to identify the mechanical sensor(s) and mechanotransduction pathway in OSNs.…”

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confidence: 98%

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

Connelly

Grosmaître

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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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. , but our understanding of the mechanical sensors is still limited. We previously discovered that some OSNs in the mammalian nose responded to mechanical stimulation (4), a feature that may allow the nose to carry an afferent signal of breathing to the brain and facilitate binding of orofacial sensation (5). In the current study, we aim to identify the mechanical sensor(s) and mechanotransduction pathway in OSNs.In mammals, smell perception depends on a large family of ORs expressed in OSNs. Out of a repertoire of >1,000 ORs (6, 7), each OSN expresses a single type, which determines its response profile and central target in the brain. Binding of odorant molecules with specific ORs activates the olfactory G protein G olf , which in turn activates type III adenylyl cyclase (ACIII). ACIII activation causes increased production of cAMP, which opens a cyclic nucleotide-gated cation (CNG) channel. The inward current via the CNG channel is further amplified by Cl − outflow through a calcium-activated Cl − channel. This transduction cascade leads to depolarization of OSNs, which fire action potentials carrying the odor information to the brain (8). OSNs expressing the same OR are scattered in one of the few broadly defined zones in the olfactory epithelium, but their axons typically converge onto a pair of glomeruli in the olfactory bulb (9).Here we report that disruption of the olfactory signal transduction cascade completely eliminates mechanical responses in OSNs. OSNs expressing different receptor types display differential responses to mechanical stimuli. For instance, I7, M71, and SR1 neurons have much stronger mechanical responses than MOR23 and mOR-EG neurons. Loss-of-function mutation of the I7 receptor, genetic switch of the M71 receptor, or ablation of the SR1 receptor, abolishes or dramatically reduces mechanical responses in the host OSNs. Furthermore, ectopic expression of the I7 receptor restores mechanosensitivity in loss-of-function mutant I7 cells. ...

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 98%

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

Connelly

Grosmaître

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…These circuits for breathing have remarkable adaptive and emergent properties (Devinney et al 2013;Lindsey et al 1992Lindsey et al , 2012Ramirez et al 2012) and participate in the generation of numerous other behaviors (Bartlett and Leiter 2012), including vocal communication (McLean et al 2013), coughing and swallowing, and their coordinated expression as a metabehavioral response to aspiration Shannon et al 2000). Breathing may also bind orofacial sensations (Kleinfeld et al 2014) and be involved in hippocampal processes for learning and memory (Lockmann and Belchior 2014).…”

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confidence: 99%

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network

Segers

Nuding

Ott

et al. 2015

Journal of Neurophysiology

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113: 352-368, 2015. First published October 15, 2014 doi:10.1152/jn.00542.2014.-Models of brain stem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that "tonic" pericolumnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multielectrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by crosscorrelogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pairwise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In five animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons.

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“…Presumably, the clock could function as part of a larger circuit that involves interactions between motor and premotor neuronal centers, as well as environmental and proprioceptive feedback signals. For the case of exploratory movements, the use of a common clock to actively sample the sensory environment could simplify the problem of binding inputs arising from different modalities, e.g., smell, touch, and taste (Kleinfeld et al 2014). …”

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confidence: 99%

The Brainstem Oscillator for Whisking and the Case for Breathing as the Master Clock for Orofacial Motor Actions

Kleinfeld

Moore

Wang

et al. 2014

Cold Spring Harb Symp Quant Biol

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Whisking and sniffing are predominant aspects of exploratory behavior in rodents. We review evidence that these motor rhythms are coordinated by the respiratory patterning circuitry in the ventral medulla. A recently described region in the intermediate reticular zone of the medulla functions as an autonomous whisking oscillator, whose neuronal output is reset upon each breath by input from the preBötzinger complex. Based on similarities between this neuronal circuit architecture and that of other orofacial behaviors, we propose that the preBötzinger complex, which projects broadly to premotor regions throughout the intermediate reticular zone of the medulla, functions as a master clock to coordinate multiple orofacial actions involved in exploratory and ingestive behaviors. We then extend the analysis of whisking to the relatively slow control of the midpoint of the whisk. We conjecture, in a manner consistent with breathing as the “master clock” for all orofacial behaviors, that slow control optimizes the position of sensors while the breathing rhythms provides a means to perceptually bind the inputs from different orofacial modalities.

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More than a rhythm of life: breathing as a binder of orofacial sensation

Cited by 97 publications

References 52 publications

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

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

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network

The Brainstem Oscillator for Whisking and the Case for Breathing as the Master Clock for Orofacial Motor Actions

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