The olfactory system is responsible for the sense of smell, also known as olfaction. The act of smelling is deceptively simple. With a single sniff, the average human is capable of discriminating between millions of different odors with little or no training, and with little regard for the chemical or physical properties of odor molecules. Olfaction is considered to be one of the oldest senses, and it can be traced back through the genetic record as one of the earliest sensory systems used by an organism to interact with its environment. For example, smells can help identify potential mates or competitors, find prey and other food sources, and identify places to live. Mammals also use their sense of smell as an advanced warning system to detect environmental hazards, such as spoiled food, smoke, leaking natural gas, airborne pollutants, or the presence of predators. Notably, mammals, and particularly humans, use their sense of smell to determine the flavor of foods and beverages. This is why it is very difficult or almost impossible to taste anything when a person has a cold (other than the sweet, salty, bitter, or sour information relayed by the tongue). Any deviation in the ability to smell can adversely impact one’s quality of life, influence what and how much one eats, whom one talks to, and where one may go.
Across species, animals use very similar cellular and molecular strategies to detect odors. In both invertebrate and vertebrate animals, the primary sensory cells responsible for detecting odorants are bipolar neurons with cilia or microvilli on one end and a typically unbranched axon at the other end. These sensory neurons are wired into the nervous system in a remarkably similar fashion: each sensory cell sends an axon to a spherical structure in the olfactory bulb called a glomerulus. At the molecular level, the proteins used to detect odorants belong to the odorant receptor family, which are all G protein—coupled receptors. These proteins have seven transmembrane domains and activate G protein—based signaling cascades, which can amplify the molecular signal. Mammals and reptiles often split their olfactory systems into two parallel systems: the main olfactory system and the accessory olfactory system. The main olfactory system detects airborne volatile chemicals, while the accessory olfactory system can detect both volatile chemicals and nonvolatile proteins or hydrocarbons.
Jelly Belly® Experiment
Before a person takes a bite of pizza, Hawaiian-style with ham and pineapple, they smell the rich aroma and their nose can distinguish the different notes of the foods that make up the pizza. This perception of odors enters the nose during sniffing, also called orthonasal olfaction. Taking that first bite, a person tastes the sweetness of the pineapple, the saltiness of the meat, and the savoriness of the cheese. A person will also perceive the food’s odorants through chewing and eating, which is retronasal olfaction where odors enter the nose via the pharynx. Together these tastants stimulate the gustatory system and the odorants stimulate the olfactory system. Thus, the chemical senses of both the taste and olfactory systems are necessary for the ability to perceive flavors of foods and beverages.
The sense of smell is the most important chemical sense for flavor to be distinguished. This is why food does not taste as flavorful when a person has a stuffy or runny nose from a head cold, flu, or sinusitis. Anosmia is the inability to smell, whether the instance is acute (temporary) or chronic (permanent). Any deviation in a person’s ability to smell can adversely impact their quality of life and influence what and how much they eat. However, it is important to note that the sense of taste is still intact, and a person with a cold or anosmia can still sense sweet, salty, bitter, umami, or sour information that is relayed by the tongue.
Jelly Belly® candies have significant amounts of odorants trapped within them, which makes the flavor of the bean more intense compared to other candies. However, other foods can be used for this experiment.
A variety of flavors of Jelly Belly® jelly beans or other highly flavored candies
For best results, make sure your nasal passage is clear and that you can take a deep breath. With one hand, plug your nose. Place the Jelly Belly® (or other food) in your mouth and chew about 5—10 times with your nose still plugged. You should only be able to taste if the food is bitter, salty, sour, and/or sweet. Unplug your nose, as this will allow retronasal olfaction to take place. Instantly, you should be able to identify the flavor of the Jelly Belly® bean.
Jennifer L. Hellier
Main Olfactory System
In the vertebrate main olfactory system, the primary sensory neurons (called olfactory sensory neurons, OSNs) are found in specialized tissue called the main olfactory epithelium (MOE), which lines a portion of the nasal passage. OSNs have a long dendrite capped by a tuft of tiny hair-like cilia, which protrude directly into the mucosal lining that covers the olfactory epithelium and are directly exposed to ambient air. Odor molecules enter the nasal passage and bind to proteins that are bound in the cilia membrane. These proteins then activate the signal transduction machinery responsible for creating a signal that indicates that an odor has been detected. The brain tissue responsible for the initial processing of this odor signal is called the main olfactory bulb (MOB). Several distinct layers make up the MOB. The outermost layer contains the olfactory nerve, which is the first cranial nerve pair (cranial nerve I). Beneath this outer nerve layer is the inner nerve layer, then the glomerular layer, the external plexiform layer, the mitral cell layer, the internal plexiform layer, and finally the granule cell layer. The granule cell layer is the innermost layer found at the center of the olfactory bulb.
From the MOE, the OSN cell body extends a single axon through the bone between the eyes and into the surface of the MOB. This axon synapses directly onto mitral cells and tufted cells in a spherical tangle of axons and dendrites called a glomerulus. In coronal sections of the olfactory bulb, these circular glomeruli can be found just inside the perimeter of the tissue cross-section. Each glomerulus represents a massive convergence of olfactory information as axons from tens of thousands of OSNs synapse onto only 25 mitral cells in a given glomerulus. Moreover, only axons from OSNs that express the same odorant receptor type converge on the same glomerulus. Each OSN responds to a limited number of odor features, which is determined by its odorant receptor type. For example, the smell of “apple” actually contains thousands of different odor features and will activate millions of different OSNs. OSNs that have the same odorant receptor type will respond to just one of these odor features and will synapse in the same glomerulus in the MOB. Similarly, a different odor feature in the apple smell will activate a different population of OSNs that will target a different glomerulus. Thus, the collective OSN response to the apple smell will activate a specific pattern of glomeruli across the surface of the MOB. This signal is then integrated and modulated by the large number of interneurons found in the different layers of the MOB, including periglomerular cells and granule cells. This signal is then relayed via the mitral cells to the regions of the brain where the apple smell will be perceived.
Mitral cell axons are the main output of the MOB and leave via the lateral olfactory tract (LOT). The LOT targets five distinct regions of the brain: the anterior olfactory nucleus, olfactory tubercle, amygdala, piriform cortex, and entorhinal cortex. Most of these targets are part of the limbic system, which are the memory and emotional centers of the brain. These direct connections into the limbic system are the reasons why smells rarely are neutral, meaning odors tend to be either attractive or repellent to a person or animal. It is also why certain smells are often associated with strong memories; for example, the smell of a rose or violets might bring back memories of a grandmother. Interestingly, the MOB receives more inputs from the rest of the brain than the number of outputs that leave the bulb. Although these inputs coming from the cerebrum are thought to modulate olfactory behavior, their anatomical and functional significance remains unclear.
Mammalian odorant receptors (OR) are proteins that specialize in detecting and responding to specific chemical signals known as odorants. An easily recognizable odor, such as “apple,” is actually a complex mixture of many different odorants at varying concentrations. A given OR type (defined by its genetic code) will often respond to just a small subset of the different odorants that make up the “apple” smell, and a distinct OR (one with a slightly different protein sequence) will respond to a different subset of the odorants.
OR proteins can be found bound to the cell membrane in the cilia of the OSN. Each OR protein is made from a gene that belongs to a relatively large family of similar genes (gene family), and each OR gene codes for a slightly different OR protein that is sensitive to only a limited number of odorants. The mammalian OR gene family is the largest gene family found in any species. In fact, it represents 1—5 percent of the entire mammalian genome. For example, humans have nearly 500 genes devoted to detecting odor molecules. Since there are only about 30,000 genes in the human genome, nearly 1 in every 50 genes is devoted to a person’s sense of smell.
ORs belong to a family of specialized receptors that are known as G protein—coupled receptors. Each OR can be likened to a tiny molecular lock that can be opened by a small, specific number of odorants. The binding of an odorant by an OR initiates a signal transduction cascade by changing the shape of the receptor protein. This conformational change releases a coupled G protein, specifically Golf, which then binds to adenylase cyclase. This cascade causes multiple biochemical reactions in the cilia that ultimately produces an action potential, which is relayed to the glomerulus in the MOB.
Only one OR gene from the entire OR gene family is expressed in any given OSN, so the entire neuron responds only to the odorants detected by the expressed OR in that cell, such as a few of the chemicals that make up the “apple” smell. OSNs expressing the same odorant gene all send signals from their axons to the same glomerulus in the MOB. This means that each glomerulus receives axons from neurons that have the same OR and are sensitive to the same set of odorants. In this way, each glomerulus integrates axonal activity from OSNs that all respond to the same odor signal. As such, each glomerulus functions as an independent processing unit in a complex topographical map of OSN activation found on the surface of the MOB. This map is known as an odor map, and different odors generate different odor maps.
The Accessory Olfactory System
An accessory olfactory system (AOS) can be found in many animals, excluding humans. This system is designed to detect nonvolatile chemical cues, often including pheromones, and requires direct contact with the odor source. In this system, the primary sensory neurons are contained within a vomeronasal organ (VNO). The VNO extends its axons to the accessory olfactory bulb. The VNO contains a vascular pump that delivers stimuli through a thin duct into the lumen within the VNO that houses the sensory neurons. The AOS differs in the types of receptor proteins and components of the signal transduction cascade that it uses to detect and respond to odor stimuli. The VNO is typically used to detect important social and sexual information, and it plays an important role in sexual reproduction and social interactions.
See also: Anosmia; Buck, Linda; Dysosmia; G Proteins; Interrelatedness of Taste and Smell; Limbic System; Olfactory Bulb; Olfactory Mucosa; Olfactory Nerve; Olfactory Reference Syndrome; Olfactory Sensory Neurons; Phantosmia; Pheromones
Buck, Linda, & Richard Axel. (1991). A novel multigene family may encode odorant receptors: A molecular basis for odor recognition. Cell, 65(1), 175—187.
Finger, Thomas E., Wayne L. Silver, & Diego Restrepo. (2000). The neurobiology of taste and smell. New York, NY: Wiley-Liss.
Mombaerts, Peter. (2001). How smell develops. Nature Neuroscience, 4, 1192—1198.