Papers relevant to the olfactory nerve - limbic system sensitization hypothesis of UARS

[nataliezzz]

The effects of nasal anesthesia on breathing during sleep
D P White, R J Cadieux, R M Lombard, E O Bixler, A Kales, C W Zwillich
https://pubmed.ncbi.nlm.nih.gov/4062052/
Sci-Hub link: https://sci-hub.st/10.1164/arrd.1985.132.5.972

Inability to breathe through the nose is an increasingly recognized cause of disordered breathing during sleep. To test the hypothesis that this respiratory dysrhythmia could result from loss of neuronal input to respiration from receptors located in the nose, we anesthetized the nasal passages of 10 normal men during sleep. Each subject spent 4 consecutive nights in the sleep laboratory while sleep stages, breathing patterns, respiratory effort, and arterial oxygen saturation were monitored. Night 1 was for acclimatization with Nights 3 and 4 being randomized to nasal spraying with either 4% lidocaine or placebo. On the lidocaine and placebo nights (Nights 3 and 4) the nasal passages were also sprayed with a decongestant to prevent increased nasal air-flow resistance resulting from mucosal swelling. To control for the possible effects of this decongestant, an additional night (Night 2) was included during which the nasal passages were sprayed with room air. Parallel studies conducted during wakefulness demonstrated low nasal resistance during the lidocaine-decongestant regimen. Because of the short duration of anesthesia with lidocaine, spraying was done at lights out and 2.5 and 5 h later. On the placebo night (decongestant plus saline) there were 6.4 +/- 1.8 (SEM) disordered breathing events (apneas plus hypopneas) per subject, whereas with lidocaine (plus decongestant) this increased fourfold to 25.8 +/- 7.8 events per subject (p less than 0.05). The majority of the disordered breathing events were apneas and were fairly evenly distributed between central and obstructive events. The magnitude of these changes is similar to that previously reported with complete nasal obstruction. These results suggest that nasal receptors sensitive to air flow may be important in maintaining breathing rhythmicity during sleep.

 

[nataliezzz]

This is going to be part of a thread on the olfactory nerve - limbic system sensitization hypothesis of UARS (link is to updated AI summary of the UARS theory) -- stay tuned. To read about the hypothesis in the meantime, see here (Bluesky thread link).

 

[nataliezzz]

Dual functions of mammalian olfactory sensory neurons as odor detectors and mechanical sensors
Xavier Grosmaitre, Lindsey C Santarelli, Jie Tan, Minmin Luo, Minghong Ma
https://pmc.ncbi.nlm.nih.gov/articles/PMC2227320/ (PDF available)

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 odor-free 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.

 

[nataliezzz]

Some evidence for a mechanical receptor in olfactory function
Showa Ueki, Edward F. Domino
https://journals.physiology.org/doi/abs/10.1152/jn.1961.24.1.12
Sci-Hub link: https://sci-hub.st/10.1152/jn.1961.24.1.12

There was no abstract; here is the summary at the end of the paper:

In dogs and monkeys with chronically implanted electrodes, bursts of electrical activity were recorded in the olfactory structures including the olfactory bulb, olfactory striae, amygdala, and pyriform cortex. These waves of 20-40 c./sec. were synchronous with inspiration in the monkey and with inspiration and expiration in dogs. The phenomena were predominantly ipsilateral. Electrical activity of similar frequencies could be elicited by blowing room air, various gases and solutions into the nostril. It appeared that a mechanical component was involved in these phenomena. Therefore studies in acute dogs given local anesthesia and immobilized with decamethonium and placed on artificial respiration were undertaken. With the use of a gas purification system evidence was obtained that in about 50% of the dogs studied electrical discharges were recorded in the olfactory bulb to odor-free oxygen, nitrogen, and carbon dioxide passed through the ipsilateral nostril. The electrical discharges in the olfactory bulb to odor-free gases were dependent upon the velocity of gas flow. The areas in the olfactory bulb where mechanical responses were obtained were relatively few compared to those areas responding to odors. In all of the animals studied the electrical responses to all odors including tobacco smoke were enhanced with increasing flows of oxygen when the flow of the odoriferous material was kept constant. Thus the concentration of odor per unit volume of gas was actually decreased at a time when the olfactory bulb responses were markedly enhanced. It is concluded that preliminary evidence has been obtained for the existence of a mechanical receptor in olfactory function.

 

[nataliezzz]

Activating effect of nasal and oral hyperventilation on epileptic electrographic phenomena: reflex mechanisms of nasal origin
Z Servít, M Kristof, A Strejcková

https://onlinelibrary.wiley.com/doi/10.1111/j.1528-1157.1981.tb04116.x

Sci-Hub link: https://sci-hub.st/10.1111/j.1528-1157.1981.tb04116.x

In experiments on animals, airflow through the nasal cavity elicits rhythmic synchronized activity that can trigger and/or elicit epileptic electrographic activities in the limbic structures of the brain. This could be demonstrated in studies of lower vertebrates (frogs and turtles). In the turtle the elicited paroxysmal activity often had the shape of regular high-voltage activity in the theta-frequency range (average frequency, 4.1 Hz). It was further proven in clinical experiments that nasal deep breathing with a closed mouth effectively activates epileptic electrographic phenomena of a temporal (limbic) origin. The activating effect was more pronounced on the side ipsilateral to the ventilated nasal meatus. It could also be evoked by air insufflation into the nasal cavity. This effect was suppressed by anesthesia of the mucous membrane in the upper nasal meatus. Possible mechanisms of this, probably reflex, phenomenon are discussed.

 

[nataliezzz]

Ultra-slow mechanical stimulation of olfactory epithelium modulates consciousness by slowing cerebral rhythms in humans
A Piarulli, A Zaccaro, M Laurino, D Menicucci, A De Vito, L Bruschini, S Berrettini, M Bergamasco, S Laureys , A Gemignani
https://pmc.ncbi.nlm.nih.gov/articles/PMC5919905/ (PDF available)

The coupling between respiration and neural activity within olfactory areas and hippocampus has recently been unambiguously demonstrated, its neurophysiological basis sustained by the well-assessed mechanical sensitivity of the olfactory epithelium. We herein hypothesize that this coupling reverberates to the whole brain, possibly modulating the subject’s behavior and state of consciousness. The olfactory epithelium of 12 healthy subjects was stimulated with periodical odorless air-delivery (frequency 0.05 Hz, 8 s on, 12 off). Cortical electrical activity (High Density-EEG) and perceived state of consciousness have been studied. The stimulation induced i) an enhancement of delta-theta EEG activity over the whole cortex mainly involving the Limbic System and Default Mode Network structures, ii) a reversal of the overall information flow directionality from wake-like postero-anterior to NREM sleep-like antero-posterior, iii) the perception of having experienced an Altered State of Consciousness. These findings could shed further light via a neurophenomenological approach on the links between respiration, cerebral activity and subjective experience, suggesting a plausible neurophysiological basis for interpreting altered states of consciousness induced by respiration-based meditative practices.

 

[nataliezzz]

Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function
Christina Zelano, Heidi Jiang, Guangyu Zhou, Nikita Arora, Stephan Schuele, Joshua Rosenow, Jay A Gottfried
https://pmc.ncbi.nlm.nih.gov/articles/PMC5148230/ (PDF available)

The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2–12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16–0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior.

SIGNIFICANCE STATEMENT Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence for respiratory entrainment of local field potential activity in human piriform cortex, amygdala, and hippocampus. These effects diminished when breathing was diverted to the mouth, highlighting the importance of nasal airflow for generating respiratory oscillations. Finally, behavioral data in healthy subjects suggest that breathing phase systematically influences cognitive tasks related to amygdala and hippocampal functions.