Sniffing is a perceptually-relevant behavior, defined as the active sampling of odors through the

nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nas ...

for the purpose of information acquisition. This behavior, displayed by all terrestrial vertebrates, is typically identified based upon changes in respiratory frequency and/or amplitude, and is often studied in the context of odor guided behaviors and olfactory perceptual tasks. Sniffing is quantified by measuring intra-nasal pressure or flow or air or, while less accurate, through a strain gauge on the chest to measure total respiratory volume. Strategies for sniffing behavior vary depending upon the animal, with small animals (rats, mice, hamsters) displaying sniffing frequencies ranging from 4 to 12 Hz but larger animals (humans) sniffing at much lower frequencies, usually less than 2 Hz. Subserving sniffing behaviors, evidence for an "olfactomotor" circuit in the brain exists, wherein perception or expectation of an odor can trigger brain

respiratory center The respiratory center is located in the medulla oblongata and pons, in the brainstem. The respiratory center is made up of three major respiratory groups of neurons, two in the medulla and one in the pons. In the medulla they are the dorsal ...

to allow for the modulation of sniffing

frequency Frequency is the number of occurrences of a repeating event per unit of time. Frequency is an important parameter used in science and engineering to specify the rate of oscillatory and vibratory phenomena, such as mechanical vibrations, audio ...

and

amplitude The amplitude of a periodic variable is a measure of its change in a single period (such as time or spatial period). The amplitude of a non-periodic signal is its magnitude compared with a reference value. There are various definitions of am ...

and thus acquisition of odor information. Sniffing is analogous to other stimulus sampling behaviors, including visual saccades, active touch, and whisker movements in small animals (viz., whisking). Atypical sniffing has been reported in cases of neurological disorders, especially those disorders characterized by impaired motor function and olfactory perception.

Background and history of sniffing

Background

The behavior of sniffing incorporates changes in air flow within the

nose A nose is a sensory organ and respiratory structure in vertebrates. It consists of a nasal cavity inside the head, and an external nose on the face. The external nose houses the nostrils, or nares, a pair of tubes providing airflow through the ...

. This can involve changes in the depth of

inhalation Inhalation (or inspiration) happens when air or other gases enter the lungs. Inhalation of air Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...

and the frequency of inhalations. Both of these entail modulations in the manner whereby air flows within the nasal cavity and through the nostrils. As a consequence, when the air being breathed is odorized, odors can enter and leave the nasal cavity with each sniff. The same applies regardless of what gas is being inhaled, including

toxins A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

and solvents, and other industrial chemicals which may be inhaled as a form of drug or

substance abuse Substance misuse, also known as drug misuse or, in older vernacular, substance abuse, is the use of a drug in amounts or by methods that are harmful to the individual or others. It is a form of substance-related disorder, differing definition ...

. The act of sniffing is considered distinct from respiration on several grounds. In humans, one can assess the occurrence of a sniff based upon volitional control of air movement through the nose. In these cases, human subjects can be asked to inhale for a certain amount of time, or in a particular pattern. Some animals are obligate nasal breathers, wherein the only air for respiration must arrive into the lungs via the nose. This includes rats and mice. Thus, in these animals the distinction between a breath and a sniff is not clear and could be argued to be indistinguishable. (See sniffing in small animals.) Sniffing is observed among all terrestrial vertebrates, wherein they inhale environmental air. Sniffing may also occur in underwater environments wherein an animal may exhale air from within its

lungs The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...

and nasal cavity to acquire odors within an aquatic environment and then re-inhale this air. (See sniffing in small animals.) While sniffing behavior is often observed and discussed within the context of acquiring odor information, sniffing is also displayed during the performance of motivated behaviors and upon deep brain electrical stimulation of brain reward centers. For instance, prior to obtaining a food reward, mice and rabbits increase their sniffing frequency in a manner independent of seeking odor information. Sniffing behavior is also displayed by animals upon involuntary electrical stimulation of numerous brain structures. Thus, while sniffing is often considered a critical part of

olfaction The sense of smell, or olfaction, is the special sense through which smells (or odors) are perceived. The sense of smell has many functions, including detecting desirable foods, hazards, and pheromones, and plays a role in taste. In humans, ...

, its link with motivated and reward behaviors suggests it plays a role in other behaviors.

History

Studies into the perceptual correlates of sniffing on human olfaction did not reach the mainstream scientific community until the 1950s. Frank Jones, an American psychologist, published a paper demonstrating the interplay between parameters of sniffing and odor detection thresholds. He found that deep sniffs, consisting of a large volume of air, allowed for consistent and accurate detection of odors. One of the earliest reports of exploring sniffing in non-human animals was provided by Welker in his 1964 article, Analysis of sniffing in the albino rat. In this study, Welker used video recordings of rats during presentation with odors and other stimuli to explore the chest movements as an index of sniffing. This was the first paper to report that rats can sniff at frequencies reaching 12 Hz upon detection of odors and during free exploration. This paper also provided early evidence that the rhythm of sniffing was coupled with other sensory behaviors, such as whisking, or the movement of the whiskers. While behavioral and psycho-physical studies into sniffing and its influence on odor perception began to surface, much less work was being performed to explore the influence of sniffing behaviors on the physiological processing of odors within the brain. Early recordings from the

olfactory bulbs The olfactory bulb (Latin: ''bulbus olfactorius'') is a grey matter, neural structure of the vertebrate forebrain involved in olfaction, the sense of odor, smell. It sends olfactory information to be further processed in the amygdala, the orbitof ...

of hedgehogs by Lord

Edgar Adrian Edgar Douglas Adrian, 1st Baron Adrian (30 November 1889 – 4 August 1977) was an English electrophysiologist and recipient of the 1932 Nobel Prize for Physiology, won jointly with Sir Charles Sherrington for work on the function of neuron ...

, who previously won the 1932 Nobel Prize along with Sir Charles Sherrington for their work on the functions of neurons, revealed that neural oscillations within the hedgehog olfactory bulb were entrained to the respiratory cycle. Further, odor-evoked oscillations (including an exhaled puff from a pipe), were amplified along with the respiratory cycle. These data gave evidence that information processing within the brain, particularly that of odors, was linked with respiration - establishing the integral nature of sniffing for the physiological processing of odors. About 20 years later, Max Mozell published a series of studies wherein he further proposed that the flow rate and the sorption properties of odorants interplay to affect the location of odorant binding to

olfactory receptor neuron An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. Structure Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are Bi ...

s in the nose and consequentially odor input to the brain. Later, evidence that single neurons in the olfactory bulb, the brain's first relay station for odor information, are entrained with respiration was presented, establishing a solid basis for the control of odor input to the brain and the processing of odors by sniffing.

Methods for quantifying sniffing

There are multiple methods available for measuring sniffing. While these methods are applicable for most animal models (mice to humans), selection of appropriate sniff measurement methods should be determined by experimental need for precision.

Video

Perhaps the simplest method for determining the moment of sniffing is video-based. High resolution video of small animals (e.g., rats) during immobile respiration enables approximations of sniffing, including identification of individual sniff events. Similar methods can be employed to identify fast, high frequency sniffing during states of arousal and stimulus investigation. This method, however, does not provide direct evidence for sniffing and is not reliable in larger animals (rabbits to humans).

Chest strain

Sensors to measure chest expansion during inhalation provide direct information of sniff cycles. These methods include mechanical and optical devices. Mechanical devices for sniffing measurements are piezo foils placed under the chests of small animals and

strain gauge A strain gauge (also spelled strain gage) is a device used to measure Deformation (mechanics)#Strain, strain on an object. Invented by Edward E. Simmons and Arthur C. Ruge in 1938, the most common type of strain gauge consists of an Electrical in ...

around the chests of larger animals. In both cases, a positive increase in signal output (voltage) can be identified and used to index inhalation events. Alternatively, a photo

transducer A transducer is a device that Energy transformation, converts energy from one form to another. Usually a transducer converts a signal in one form of energy to a signal in another. Transducers are often employed at the boundaries of automation, M ...

can be placed on the opposite side of an animal's chest from a light source (e.g., a

Light-emitting diode A light-emitting diode (LED) is a semiconductor device that emits light when current flows through it. Electrons in the semiconductor recombine with electron holes, releasing energy in the form of photons. The color of the light (corre ...

). In this design, a decrease in signal reflects inhalation (chest expansion) as the chest would interrupt the light passage to the photo transducer.

Nasal microphone

As a direct measurement of sniffing, early studies favored the use of microphones placed/secured external to the anterior nares, the external openings of the

. This method has advantages to directly index air leaving the nares (increase in microphone output), yet is mostly non-invasive. Due to this non-invasive nature of microphone measures, these methods have been employed in dogs during odor tracking exercises and are useful for measuring sniffing on a temporary basis in other large animals.

Nasal thermocouple and nasal pressure sensor

The most precise methods to date to measure sniffing involve direct intranasal measures through use of a temperature probe, called a

thermocouple A thermocouple, also known as a "thermoelectrical thermometer", is an electrical device consisting of two dissimilar electrical conductors forming an electrical junction. A thermocouple produces a temperature-dependent voltage as a result of the ...

, or a pressure sensor. These can be inserted temporarily into the nares or implanted surgically. The basic principles of operation are shared between the temperature and pressure devices. Inhalation of ambient air provides cool temperature into the nasal cavity, whereas exhalation of inhaled air provides warm temperature into the nasal cavity and simultaneously an increase in intranasal pressure as air from the lungs is forced out of the nostrils. Placement of these sensors close to the

olfactory epithelium The olfactory epithelium is a specialized epithelium, epithelial tissue inside the nasal cavity that is involved in olfaction, smell. In humans, it measures and lies on the roof of the nasal cavity about above and behind the nostrils. The olfact ...

of animals allows measures of odorized air transients as they reach the

olfactory receptor Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give ...

s and thus are common methods for measuring sniffing in the context of

sensory neuroscience Sensory neuroscience is a subfield of neuroscience which explores the anatomy and physiology of neurons that are part of sensory systems such as vision, hearing, and olfaction. Neurons in sensory regions of the brain respond to stimuli by firi ...

and psychological studies.

Sniffing in small animals

The earliest published study of sniffing behavior in small animals was performed in

laboratory rat Laboratory rats or lab rats are strain (biology), strains of the rat subspecies ''Rattus norvegicus domestica'' (Domestic Norwegian rat) which are bred and kept for scientific research. While Animal testing on rodents, less commonly used for re ...

s using video-based measures. In this study robust changes in respiratory frequency were reported to occur during exploration of an open arena and novel odors. Resting respiration occurs ~2 times/second (Hz), and increases to about 12 Hz are noted during states of exploration and arousal. Similar transitions in sniffing frequency are observed in freely exploring mice, which, however, maintain generally higher sniffing frequencies than rats (3 estto 15 Hz xplorationvs 2 to 12 Hz). Transitions in sniffing frequency are observed in animals performing odor-guided tasks. Studies of recording sniffing in the context of odor-guided tasks involve implanting intranasal temperature and pressure sensors into the nasal cavity of animals and either measuring odor-orienting responses (fast sniffing) or sniffing during performance in operant odor-guided tasks. Alternatively, animals can be conditioned to insert their

snout A snout is the protruding portion of an animal's face, consisting of its nose, mouth, and jaw. In many animals, the structure is called a muzzle, Rostrum (anatomy), rostrum, beak or proboscis. The wet furless surface around the nostrils of the n ...

s into an air-tight chamber with a pressure transducer embedded within to access nasal transients, while simultaneously odors are presented to measure responses while nose-poking. Notably, several studies have reported that modulation in sniffing frequency may be just as great in context of anticipation of odor sampling as during sampling of odors. Similar changes in sniffing frequency are even seen in animals presented with novel auditory stimuli, suggesting a relationship between sniffing and arousal.

Sniffing in semi-aquatic animals

While sniffing is generally thought to occur solely in terrestrial animals, semi-aquatic rodents ( American water shrew) also display sniffing behaviors during underwater odor-guided tasks. Shrews inhale-exhale small amounts of air in a precise and coordinated fashion while tracking an underwater odor trail. This occurs through the inhalation of air above ground, to allow air to volatilize odors in an environment otherwise void of air.

Sniffing and control of odor input to the brain

Measurements of sniffing simultaneously with physiological measures from olfactory centers in the brain have provided information on how sniffing modulates the access and processing of odors at the neural level. Inhalation is necessary for odor input to the brain. Further, odor input through the brain is temporally linked to the respiratory cycle, with bouts of activity occurring with each inhalation. This linkage between sniffing frequency and odor processing provides a mechanism for the control of odor input into the brain by respiratory frequency and possibly amplitude, though this is not well established.

Sniffing in humans

The nature of sniffing regulates odor

perception Perception () is the organization, identification, and interpretation of sensory information in order to represent and understand the presented information or environment. All perception involves signals that go through the nervous syste ...

in humans and in fact, in humans, a single sniff is often sufficient for optimal odor perception. For instance, a deep, steady inhalation of a faint odor allows a more potent percept than a shallow inhalation. Similarly, more frequent sniffs provide a faster percept of the odor environment than only sniffing once every 3 seconds. These examples have been supported by empirical studies (see above) and have provided insights into methods whereby humans may change their sniffing strategies to modulate odor perception. Odor inhalation evokes activity throughout olfactory structures in humans.

Neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the neuroanatomy, structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive ...

studies lack resolution to determine the impacts of sniffing frequency on the structure of odor input through the brain, although imaging studies have revealed that the motor act of sniffing is anatomically independent of sniff-evoked odor perception. Implications for this include the shared but distributed pathways for odor processing in the brain.

Neural control of sniffing

Sniffing is fundamentally controlled by

s in the

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

, including the Pre-Botzinger complex which governs inhalation/exhalation patterns. Activity from respiratory brain stem structures then modulates nervous activity to control lung contraction. To exert changes to respiration, and thereby evoke sniffing behavior, volitional centers in the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

must stimulate brain stem structures. It is through this simple pathway that the decision to inhale or sniff may occur. The rapid modulation of sniffing upon inhalation of a novel odor or an irritating odor is evidence for an "olfactomotor" loop in the brain. In this loop, novel odor-evoked sniffing behavior can occur rapidly upon perception of a novel odor, one of interest, or an odor which is aversive.

Relation of sniffing to other stimulus sampling behaviors

Sniffing, as an active sampling behavior, is often grouped along with other behaviors utilized to acquire sensory stimuli. For instance, sniffing has been compared to rapid eye movements, or

saccade In vision science, a saccade ( ; ; ) is a quick, simultaneous movement of both Eye movement (sensory), eyes between two or more phases of focal points in the same direction. In contrast, in Smooth pursuit, smooth-pursuit movements, the eyes mov ...

s, in the ability for both methods to provide rapid "snapshots" of information to the brain. This analogy, though, may be imprecise since small animals (e.g., mice) make odor-based decisions (through sniffing) while also making visual decisions, yet do not saccade. Sniffing is also fundamentally similar to active touch, including swiping ones finger along a surface to scan texture. In part due to the interrelatedness of the respiratory brain stem structures with other central pattern generators responsible for governing some other active sampling behaviors, sniffing in animals often occurs at similar frequencies (2 to 12 Hz) and in a phasic relationship to the active sampling behaviors of whisking and licking. Whisking and sniffing are tightly correlated in their occurrence, with sniff inhalations occurring during whisker protraction. Due to the metabolic need to coordinate breathing and swallowing, small animals (rats and mice) often lick at similar frequencies of sniffing (4 to 8 Hz) and swallow in between inhalations or during brief periods of

apnea Apnea (also spelled apnoea in British English) is the temporary cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the ...

(cessation of breathing).

Relevance to neurological disorders

Few studies have explored the impact of

neurological disorder Neurological disorders represent a complex array of medical conditions that fundamentally disrupt the functioning of the nervous system. These disorders affect the brain, spinal cord, and nerve networks, presenting unique diagnosis, treatment, and ...

s on sniffing behavior, although numerous neurological disorders affect respiration. Humans with

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

have abnormal sniffing capabilities (i.e., reduced volume and flow rate) which may underlie olfactory perceptual impairments in the disease. Studies into sniffing in mouse models of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

and also humans have not found major effects of Alzheimer's pathology on both basal respiration and odor-evoked sniffing.

References

External links

Association for Chemoreception Sciences

Chemical Senses journal

Case Western Reserve University, Wesson Lab

The University of Utah, The Brain Institute, Wachowiak Lab

New York University SoM., Emotional Brain Institute, Wilson Lab

Monell Chemical Senses Center

Olfactory-auditroy integration

Odor Space
Respiration Respiratory physiology