Video: Smell

To appreciate the beauty of life, they say we need to stop and smell the roses. But, imagine if you couldn't smell anything. It may kind of sound trivial at first, but it might affect you more than you think. Smell is also tied to our memories and emotions. Behavior and bonding are more scent-driven than we give our noses credit for. Let's learn more about this in a scent-sational tutorial on our sense of smell.

Smell is one of the five special senses, and together with taste, involves the transduction of chemical stimuli into electrical signals. In the case of smell, these chemical stimuli are referred to as odorants. There are thousands of different odorants which when detected in combinations can create the perception of up to one trillion distinct smells or odors.

While humans have adapted to rely heavily on vision and hearing, our ability to detect those odorants can still dictate certain responses and influence our emotions, memories, and even our decision making. And contrary to the traditional thinking that humans have a terrible sense of smell compared to other animals like dogs or rodents, recent research in olfactory neuroscience shows we’re actually pretty great at recognizing and distinguishing odors, much better than we gave ourselves credit for.

The process of olfaction is related to cranial nerve 1, the olfactory nerve. It begins in a relatively small region of the roof of the nasal cavity, known as the olfactory part of the nasal mucosa, a 3-centimeter squared patch where odorants are detected. These are either airborne molecules inhaled via the nostrils or those which ascend from the pharynx while eating.

It contains a specialized tissue known as olfactory epithelium which contains three main cell types -- olfactory sensory neurons, supporting epithelial cells, and basal cells.

Olfactory sensory neurons are modified bipolar neurons which have a single dendrite that ends with several tiny hair-like extensions known as olfactory cilia, which project onto the nasal cavity. And it's here in these cilia where odorants are detected and transduced into electrical signals. We'll take a closer look at this in just a second.

The axons of the olfactory neurons group together to form approximately 20 olfactory fiber bundles which pass into the cranial cavity via tiny passages in the cribriform plate of the ethmoid bone. Olfactory sensory neurons are unusual in that, unlike other neuron populations, they continuously are replaced through most of adulthood until old age.

The olfactory sensory neurons are surrounded by supporting epithelial cells of varying functions. Some serve a similar role to glial cells in that they provide the olfactory sensory neurons with metabolic and physical support. Others phagocytose debris from dead olfactory sensory neurons and cells while others are able to break down certain organic chemicals and other potentially damaging molecules that enter the nasal cavity.

The final cell type in the olfactory epithelium are the basal cells, which are much smaller and located close to the basal lamina. The primary role of this cell population is to serve as precursor cells which differentiates to replace olfactory sensory neurons as well as the supporting epithelial cells.

You'll also have spotted these tubular structures here penetrating the olfactory epithelium, which are known as olfactory glands, commonly known as Bowman’s glands. These produce a continuous flow of protein-rich secretions onto the olfactory surface which serves to trap or solubilize odorants so they can be presented to specialized receptors on the olfactory cilia.

Let's take a closer look now at the mechanics of olfactory transduction.

Odorants, dissolved in the mucus, bind with olfactory receptors in the membrane of each cilium. The inside of the receptor is coupled with a G-protein, specifically, a Golf protein, which is itself composed of three subunits. When the receptor binds with an odorant, a cascade of events is triggered, beginning with the alpha subunit breaking away from the Golf protein and activating an enzyme known as adenylyl cyclase, which converts adenosine triphosphate, or ATP, into cyclic adenosine monophosphate, or cAMP.

Cyclic adenosine monophosphate, in turn, binds with ligand-gated ion channels in the cilium membrane causing them to open, allowing sodium and calcium ions to enter the cell.

Now we know when positive ions like sodium or calcium enter a neuron, it brings about changes in its membrane potential and the stimulus causes a depolarization large enough to reach a threshold potential at the axon hillock of the olfactory neuron, and an action potential is triggered, meaning the chemical stimulus has been converted or transduced into an electrical signal.

Now, as humans, we are limited to only about 400 olfactory receptor types; however, despite this, we're able to detect thousands of types of odorants. You see, each receptor type is capable of responding to a range of different, yet chemically similar odorants, and conversely, a single odorant may bind with a range of different olfactory receptors. This allows the olfactory system to encode odors through unique combinations of receptor activations, enabling us to perceive and distinguish an incredible diversity of smells.

This is also why odorants that have never been encountered before can trigger patterns of receptor activation similar to those of previously encountered odorants, allowing new odors to be characterized.

Once an odorant has been detected and transduced, neural signals carrying this information travel along the axons of olfactory sensory neurons which form fiber bundles that travel through tiny holes in the cribriform plate of the ethmoid bone. These fiber bundles are known as olfactory fiber bundles or fila olfactoria.

The axons terminate in the olfactory bulb, which is a rostral extension of the cerebrum located inferior to the frontal lobe. Here, they synapse in specialized structures known as olfactory glomeruli. Each glomerulus contains thousands of olfactory sensory neuron endings which synapse with a much smaller number of second order projection neurons, known as mitral and tufted cells.

Surrounding the olfactory glomeruli are populations of inhibitory neurons known as periglomerular cells. These primarily serve to provide modulation within the olfactory glomerulus, but also quiet down neighboring glomeruli by inhibiting nearby mitral and tufted cells. This acts as an initial filter for smell signals, helping to sharpen stronger odors and block out irrelevant ones.

Granular cells provide a second level of inhibition, providing further refinement of olfactory input. Mitral and tufted cells excite granular cells, which then inhibit nearby neurons. This is known as lateral inhibition. It serves to sharpen odor perception by increasing contrast between signals.

From the olfactory glomerulus, the axons of the projection neurons carrying smell signals leave the olfactory bulb and form a nerve-like band known as the olfactory tract. A large number of fibers from the olfactory tract are directed towards the piriform cortex, which is the largest of the olfactory cortical areas. It largely corresponds to the ambient gyrus, which is part of the uncus of the temporal lobe, with a small extension onto the caudolateral aspect of the frontal lobe also.

This is the primary cortical area for conscious olfactory processing and is responsible for odor discrimination and recognition.

Other fibers from the olfactory tract and piriform cortex are also directed to several other structures such as the olfactory or cortical part of the amygdaloid body, parts of the limbic lobe like the entorhinal cortex which is located at the parahippocampal gyrus, and as well as the hippocampus and hypothalamus.

These connections allow olfactory signals to go beyond basic recognition and extend to centers related to emotional or physiological responses to smell, like salivation or nausea, as well as formation of olfactory memories or associations. For example, when you get the smell of a freshly baked cake, it brings you right back to your favorite auntie who stuffed you with delicious cakes as a child. Or on the other hand, the smell of a certain food which made you ill in the past makes you feel nauseous when you encounter it again. This facilitates the unique connection between smell, memory, and emotion in olfaction.

A final cortical area which I would like to mention is this one here, the orbitofrontal cortex. It serves several different functions and receives fibers from many different areas; however most interesting for us today are those received from the gustatory cortex related to taste and the olfactory cortex for smell. This convergence allows the orbitofrontal cortex to combine taste and odor signals to create the perception of flavor.

It's also important to note that efferent or centrifugal fibers project from the higher regions which we just mentioned to the olfactory bulb. These fibers regulate the activity of mitral, tufted, and granular cells in the olfactory bulb and help modulate sensitivity to odors, sharpen signal processing, and support olfactory learning and memory.

And with that, we've explored the fascinating process of olfaction, from the detection of odorants by our olfactory receptors to the intricate pathways that send signals to the brain. We've seen how smell shapes our perception, memory, and even emotions.

Learn more about this topic and consolidate your knowledge now in our articles and quizzes, and I'll see you next time.