Our Chemical Senses: Olfaction

Experiment: Olfactory Fatigue

Developed by Marjorie A. Murray, Ph.D.; Neuroscience for Kids Staff Writer


[Teacher Guide] | [Student Guide]

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[Summary] | [Background Concepts] |
[Planning and Teaching the Lab] | [References] | [Science Education Standards]


Students learn how to investigate the olfactory system and then find out how to plan and carry out their own experiments. In the "CLASS EXPERIMENT," students find that the ability to detect an odor decreases with continued exposure to that odor, a property called olfactory fatigue. They learn basic facts about sensory receptors, nerve connections, and brain areas, and discover what conditions can affect olfactory fatigue.

In "TRY YOUR OWN EXPERIMENT," students design experiments to further explore the sense of smell. For example, they can investigate whether mixing two substances makes it harder to identify odors; whether gender affects the ability to identify odors, and whether people vary in their ability to match unlabeled containers of odor materials.

SUGGESTED TIMES for these activities: 45 minutes for introducing and discussing the activity, 45 minutes for the "Class Experiment;" and 45 minutes for brainstorming and "Try Your Own Experiment."


1. Overview of the smell and taste systems

Odor and food molecules activate membrane receptors

Sensations from our noses and mouths alert us to pleasure, danger, food and drink in the environment. The complicated processes of smelling and tasting begin when molecules detach from substances and float into noses or are put into mouths. In both cases, the molecules must dissolve in watery mucous in order to bind to and stimulate special receptor cells. These cells transmit messages to brain areas where we perceive odors and tastes, and where we remember people, places, or events associated with these olfactory (smell) and gustatory (taste) sensations.

The neural systems for these two chemical senses can distinguish thousands of different odors and flavors. Identification begins at membrane receptors on sensory cells, where odorant or taste molecules fit into molecular slots or pockets with the right "lock and key" fit. This latching together of ligand and membrane receptor leads to the production of an electrical signal, which speeds along a pathway formed by nerve cells (neurons) and their extensions called axons. In this way, information reaches brain areas that perceive and interpret the stimulus.

A membrane receptor will respond to several structurally related molecules

The activation of receptors by discrete chemical structures is apparently not absolute, for a given membrane receptor will respond to a group of structurally similar compounds. Probably hundreds of odor membrane receptors exist, but many fewer taste receptors, perhaps on the order of 10 or 20 (we only know of about five now). The fact that we can discriminate thousands of smells and tastes is a result of complex substances activating different combinations of odor and taste receptors. Researchers frequently test people or animals with pure chemicals in order to find the best stimulus for a receptor, but in the real world odors and foods consist of many different types of molecules.

The neural systems for taste and smell share several characteristics

Although the neural systems for taste and smell are distinct from one another, the sensations of flavors and aromas often work together, especially during eating. Much of what we normally describe as flavor comes from food molecules wafting up our noses. Further, these two senses both have connections to brain areas that control emotions, regulate food and water intake, and form certain types of memories.

Another similarity between these systems is the constant turnover of olfactory and gustatory receptor cells. After about ten days, taste receptor cells die and are replaced by cells that differentiate from a sort of stem cell in the taste bud. More surprising is the story of olfactory sensory cells. These are not epithelial cells as are taste cells, but neurons, which until recently were not known to be generated in adults. (Recent evidence shows that this can happen, even in the brain). The olfactory sensory neurons are not only replaced every 60 days or so, but each must also grow an axon to the correct place in the brain. Researchers are investigating how taste perception and odor recognition are maintained in the face of this turnover and new axon growth.

2. Odor receptors are ciliated sensory neurons in the upper nasal cavity

Humans can detect on the order of 10,000 "odorants," or substances that stimulate the sense of smell, and can detect some of these at concentrations as low as a few parts per trillion. Special olfactory receptor cells, about fifty million of them, line the upper reaches of the nasal cavity in a sheet of olfactory epithelium. Hair-like cilia dangle from the ends of the cells into the mucous layer covering the epithelium, where odor molecules bind to membrane receptors on the cilia.

What is the mechanism for distinguishing aromas? As mentioned in Section 1, membrane receptors contain molecular pockets that accommodate only compounds with certain chemical structures. When an odorant molecule binds to a receptor, an intracellular "second messenger" system (usually using cyclic AMP) is engaged. After several steps, the membrane of the nerve cell propagates an electrical signal along its length and passes it on to the next nerve cell in the pathway. The second messenger system is a signaling mechanism used in many sensory nerve cells as well as in other cells in the body.

All vertebrate olfactory receptor neurons examined so far are "generalists." In other words, they respond best to one class of substances, more weakly to another group or two, and not at all to others. Insects and some other animals possess odor "specialists" that respond only to one pure substance, that is, a single molecule. Usually this is a pheromone that is employed in finding a mate. Researchers expect to find specialist cells in vertebrates as well; these are difficult to find because there probably aren't many of them, and scientists haven't yet identified their specific ligands.

3. Olfactory signals go to two types of areas in the brain

Where do odor messages go once they activate the sensory neurons in the nasal cavity? To get to the brain, the axons of the olfactory sensory neurons must get through the skull (see side view of the skull in Figure 1 on the left). The olfactory epithelium lines the bone of the part of the skull just above the nasal passages, and the axons of the neurons pass directly through tiny holes in this bone. Here they enter the first relay station, the olfactory bulbs, one on either side of the bottom surface of the brain (Figure 2, right). The electrical signal generated when an olfactory sensory neuron is activated is passed along to a secondary neuron residing in the bulb, and from here the signal goes by way of the olfactory tract to other brain areas.

The olfactory system is often described as the most "primitive" sensory system because of its early phylogenetic development and its connections to older, subconscious portions of the brain. From the olfactory bulbs, odor messages go to several brain structures that make up the "olfactory cortex," an area that evolved before the cortical areas that give us consciousness. This part of the cortex is on the bottom surface of the brain, with some of the olfactory areas folded under the visible parts. These areas have connections to the limbic system (including the hippocampus, amygdala and hypothalamus), which is important in emotional states and in memory formation (see Figure 3). Thus, a smell frequently activates intense feelings and memories before a person even identifies the odor.

Messages also go to conscious cortical areas. After a relay in the olfactory cortex , signals enter a way station called the thalamus, and then travel on to the frontal cortex, where identification and other related thought processes take place.

Thus, odor messages go to primitive brain areas where they influence emotions and memories, and to "higher" areas where they modify conscious thought (Fig. 3, below).

FIGURE 3. Summary of olfactory pathways.
Note that not all intermediate relays are included.

4. Odors map onto specific brain areas

Because sight, sound, and touch sensations map in a spatial way onto brain areas, researchers wondered if this happens with odors. They have found that in the olfactory bulb, neurons, their cytoplasmic processes, and support cells are not evenly distributed but form clumps called glomeruli. Certain odorants activate only one or a small number of glomeruli, producing a kind of mapping, although it is not a spatial map of the location of odors in relation to the body, but a functional map of odor types. Whether this mapping is continued at higher brain levels is uncertain. A type of spatial mapping also exists in the olfactory epithelium, in the nasal passages. Here, scientists have shown that certain volatile chemicals attach to receptor cells in defined patches of epithelium and not to others.

5. Patterns of neural activity allow us to identify odors

To summarize the process of odor detection, let's follow an odorant into the nose. At 7 a.m., molecules from a cup of coffee float into the air and drift into your nose. You breathe deeply, drawing the molecules up into the top of your nasal passages. Several types of molecules are present, and each fits into a slot on a membrane receptor that can accommodate only that class of molecular structures.

As soon as the molecules stick to their receptors, intracellular systems of enzymes and substrates go into gear, quickly causing each cell to produce an electrical signal. The signal flashes through the axon of each olfactory sensory neuron and on to cells in the olfactory bulb. Each type of receptor neuron sends its signal to a specific clump of cells in the olfactory bulb, forming a sort of odor map.

From here, the message from each bulb cell zips to several places by way of branches from the cell's axon. Messages to the olfactory cortex give you that "aahhh" feeling, others activate memories of previous cups of coffee, still others wind up stimulating motor areas to cause salivation. The signals travel another pathway to your frontal cortex, which "says" to you: "COFFEE!"

The experiences of perceiving and interpreting the coffee odor are the result of activating a pattern of neural components, and in turn, specific memories, feelings, and thoughts.

6. Several mechanisms may contribute to olfactory fatigue

Adaptation, or fatigue, to constant stimulation is a general feature of sensory systems. For instance, the touch receptor cells in the skin adapt to the stimulation of our clothes, a fortunate thing, or we would be distracted by them constantly. Adaptation involves mechanisms at the level of the receptor cell, including the inactivation of ion channels in the membrane that generate the electrical signal. In a simplified explanation, after a stimulus causes a receptor cell to produce an electrical signal, the cell membrane soon stops allowing ions to flow, thus preventing further signals. Removal of the stimulus followed by restimulation activates the process all over again.

Researchers have noted that people adapt to odors, such as the smell of tobacco smoke in a room, more quickly than the properties of olfactory receptor cells would predict. Thus, they believe that olfactory fatigue involves some types of central nervous system mechanisms as well as receptor adaptation. Although these brain mechanisms are currently unknown, scientists speculate that inhibitory circuits in the brain "quash" the incoming sensory signals from receptors before they reach conscious levels.

7. Genes determine the kinds of odor receptors that we have, and experiences shape our perceptions

Olfactory abilities vary widely among individuals -- we all know someone who is able to smell things when no one else can, or someone who doesn't seem to mind an unpleasant odor when most people do. Studies have shown that people who are unable to smell one or one class of odors frequently have small genetic differences from the general population. The inability to smell is called "anosmia," and it may be general, or specific for one odor. Temporary general anosmia or "hyposmia" (lessened sense of smell) can result from a cold or certain medicines. "Hyperosmia," a heightened sense of smell, can be a genetic trait.

Previous experiences and our physiological states also affect our reactions to odors and our perceptions. The odor of frying trout or hot cocoa may smell wonderful to a hungry camper, but terrible to someone with the stomach flu. A child who remembers her mother sprinkling cinnamon on her little brother's vomit before cleaning it up may never want cinnamon cookies again, even as an adult.

Our expectations and beliefs can even affect measurements such as olfactory fatigue times. Studies have shown that the time for adapting to an odor is significantly different when people believe they are being exposed to a harmless aroma, compared to when they think they are smelling a hazardous substance, even when the odor is exactly the same.

8. Olfactory disorders may be genetic, or may result from illness or injury

While genetic differences account for some cases of anosmia or other olfactory disorders as mentioned above, most are caused by illnesses or accidents. Small growths in the nasal cavities (polyps), dental problems, hormonal disturbances, or sinus infections, as well as common colds, may cause chemosensory losses. Injury to the head may damage nerve fibers or break axons. Patients who receive radiation therapy for cancers of the head or neck often develop changes in their sense of smell.

Are these disorders serious? Our sense of smell alerts us to fires, poisonous fumes, leaking gas, and spoiled food. It can stop us from entering a dangerous area or putting something into our mouths that can make us sick. Further, such disturbances can be a signal that some other disease is present, such as Parkinson's disease, hypertension, or diabetes. People should see a doctor if they realize something is wrong with their sense of smell.

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Provide background information

First, prepare students for lab activities by giving background information according to your teaching practices (e.g., lecture, discussion, handouts, models). Because students have no way of discovering sensory receptors or nerve pathways for themselves, they need some basic anatomical and physiological information. Teachers may choose the degree of detail and the methods of presenting the olfactory system, based on grade level and time available.

Offer students the chance to create their own experiments

While students do need direction and practice to become good laboratory scientists, they also need to learn how to ask and investigate questions that they generate themselves. Science classrooms that offer only guided activities with a single "right" answer do not help students learn to formulate questions, think critically, and solve problems. Because students are naturally curious, incorporating student investigations into the classroom is a logical step after they have some experience with a system.

The "Try Your Own Experiment" section of this unit (see the accompanying Teacher and Student Guides) offers students an opportunity to direct some of their own learning after a control system has been established in the "Class Experiment." Because students are personally vested in this type of experience, they tend to remember both the science processes and concepts from these laboratories.

Use Explore Time or Brainstorming before experimenting

To encourage student participation in planning and conducting experiments, first provide Explore Time or Brainstorming Time. Because of their curiosity, students usually "play" with lab materials first even in a more traditional lab, so taking advantage of this natural behavior is usually successful.

For some experiments, such as the olfactory lab, brainstorming is probably best. In these labs, if students investigate the materials before starting the experiments, they will probably identify (or hear others identify) and memorize many of them. Further, in activities to stimulate memories associated with odors, the "surprise" element of a sudden whiff of material is important in generating an interesting experience. Instead of letting students explore, the teacher can simply indicate the lab bench, saying that the containers of odor materials will be available for experiments. When students see that opaque, unmarked containers of materials are available, they can begin to generate questions for investigations, and the teacher can offer more ideas.

Class Experiment

After students gain an interest in the materials and subject, lead the class into the Class Experiment and help them to formulate the Lab Question. (Using the Teacher Demonstration suggested in the Teacher Guide will also help students focus on the subject.) Hand out the Student Guide and any worksheets after brainstorming, so students have a chance to think on their own. (See the accompanying Guides.)

"Try Your Own Experiment"

For the Try Your Own Experiment activity, follow the procedure above, adding the new materials for student-generated experiments. Let the students suggest a variety of ideas, then channel their energies to make the lab manageable. For example, when a number of groups come up with similar ideas, help them formulate one lab question so that the groups can compare data. The goal is to encourage students to think and plan independently while providing sufficient limits to keep the classroom focused. The Teacher and Student Guides contain detailed suggestions for conducting good student-generated experiments.

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  1. Bellamy, M.L. and Frame, K. (Eds.) (1996). Neuroscience Laboratory and Classroom Activities. National Association of Biology Teachers and the Society for Neuroscience, pp. 113-136.

  2. Kandel, E.R., Schwartz, J.H., and Jessell, T.M. (Eds.) (2000). Principles of Neural Science, Fourth ed., New York: McGraw Hill Health Professions Division

  3. Shepherd, G.M. (1994). Neurobiology, Third ed. Oxford: Oxford University Press.

  4. Monell Chemical Senses Center

  5. Pines, M. (1995). The Mystery of Smell, in Seeing, Smelling, and Hearing the World, Chevy Chase, Maryland: Howard Hughes Medical Institute.

  6. The Nose Knows; Smell Experiments from Neuroscience for Kids

  7. Insect Olfaction

  8. Leffingwell and Associates, a commercial site of the flavor and fragrance industry, with good basic science information


By reaching Project 2061 Benchmarks for Science Literacy, students will also fulfill many of the National Science Education Standards and individual state standards for understanding the content and applying the methods of science. Because the Benchmarks most clearly state what is expected of students, they are used here. Below is a list of Benchmarks that can be met while teaching the olfactory sense activities. The Benchmarks are now on-line at: http://www.project2061.org/tools/benchol/bolframe.htm

The Benchmarks are listed by chapter, grade level, and item number; for instance, 1A, 6-8, #1 indicates Chapter 1, section A, grades 6-8, benchmark 1.

The process of inquiry used in the olfactory sense activities will help students reach the following summarized Benchmarks:

  • 1A, 6-8, #1: When similar investigations give different results, the scientific challenge is to judge whether the differences are trivial or significant, and it often takes further studies to decide.

  • 1B, 6-8, #1: Scientific investigations usually involve the collection of relevant evidence, the use of logical reasoning, and the application of imagination in devising hypotheses and explanations to make sense of the collected evidence.

  • 1B, 6-8, #2: If more than one variable changes at the same time in an experiment, the outcome of the experiment may not be clearly attributable to any one of the variables.

  • 12A, 6-8, #2: Know that hypotheses are valuable, even if they turn out not to be true.

  • 12A, 6-8, #3: Know that often, different explanations can be given for the same evidence, and it is not always possible to tell which one is correct.

  • 12C, 3-5, #3: Keep a notebook that describes observations made, carefully distinguishes actual observations from ideas and speculations about what was observed, and is understandable weeks or months later.

  • 12D, 6-8, #2: Read simple tables and graphs and identify the relationships they reveal.

  • 12D, 6-8, #3: Locate information in reference books, newspapers and magazines, compact discs and computer databases.

    The neuroscience content in the olfactory sense activities and background material will help to meet the following benchmarks:

  • 5C, 6-8, #1: All living things are composed of cells. Different body tissues and organs are made up of different kinds of cells. The cells in similar tissues and organs in other animals are similar to those in human beings.

  • 5C, 6-8, #2: Cells repeatedly divide to make more cells for growth and repair.

  • 6A, 6-8, #1: Like other animals, human beings have body systems for the coordination of body functions.

  • 6C, 6-8, #1: Organs and organ systems are composed of cells and help provide all cells with basic needs.

  • 6D, 6-8, #4: Attending closely to any one input of information usually reduces the ability to attend to others at the same time.

  • 6D, 6-8, #3: Human beings can detect a tremendous range of visual and olfactory stimuli.

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