Neuropsychologist Javier Esteban Libiano explains in this article all the details about how our brain encodes smells.
Smell, along with taste, is a chemical sense. The stimuli received by both senses interact with their receptors chemically.
Smell helps identify food and avoid those that are spoiled or not suitable for consumption. It helps many species track or detect predators, as well as identify friends, enemies, and receptive mates.
For humans, smells have the peculiar ability to evoke memories. Smell activates brain regions related to emotion, learning, and memory.
Could we use this information to exert a neurorehabilitative effect on different cognitive abilities in individuals with some type of brain damage or cognitive impairment associated with various pathologies?
The stimulus, nature, and characteristics
There is growing evidence that sensory stimulation has an effect on the maintenance and improvement of cognitive abilities—such as perception, language, praxis, gnosis, attention, memory, executive functions, orientation, reasoning, and motivation—in people with cognitive decline, strokes (CVA), or other factors that have caused brain damage.
The olfactory stimulus, technically known in English as odorants, consists of volatile substances with a molecular weight between 15 and 300 g/mol (grams per mole). Almost all odorant compounds are lipid-soluble and organic in origin, although many substances meeting these criteria have no smell at all.
Odoriferous substances must be water-soluble to dissolve in the superficial mucous layer and reach the olfactory cilia, where they bind to specific receptors. At sufficiently high concentrations, they cause depolarization of the cell membrane, which is transmitted through the axon as an action potential.
It is believed that there are certain basic qualities in smell that are registered by specific receptors.
Since substances within the same olfactory group have similar molecular sizes, it seems possible that the membrane of an olfactory cilium—extensions of receptor cells that penetrate the mucosa and receive stimuli—reacts only to a certain molecular size.
New research suggests that a sensory cell expresses only one type of receptor.
Research from the University of California discovered that certain smells could increase cognitive ability in people by conducting an experiment where individuals were exposed to a fragrance while sleeping. This research opens the door to non-invasive neurorehabilitative treatments to combat neurodegenerative diseases or various types of brain damage.
The receptors
We have six million olfactory receptor cells (bipolar neurons), located in two portions of the mucous membrane (the olfactory epithelium).
In humans, the olfactory epithelium covers a small area in both nasal cavities, situated at the top of the nasal cavity, on the edge of the upper turbinates and the opposite surface of the nasal septum.
The receptors for smell are found in the sensory epithelium, which is composed of supporting cells and olfactory sensory cells.
The olfactory sensory cells are bipolar neurons, whose cell bodies are in the olfactory mucosa covering the cribriform plate, a gap at the base in the rostral part of the brain.
Among the olfactory receptor cells are supporting cells, which contain enzymes that break down odor molecules, helping to prevent the olfactory receptors from being altered.
The olfactory region also contains numerous small mucous glands, known as Bowman’s glands, whose secretion forms a thin terminal film covering the olfactory mucosa.
The distal segment of the sensory cell narrows to form a slender stalk that slightly exceeds the surface of the olfactory epithelium. This olfactory protrusion is covered by numerous olfactory cilia. Proximally, the oval-shaped cell body continues with a slender extension that, along with others, is enveloped by Schwann cells.
Stimulus-receptor interaction
Researchers acknowledge that olfactory cilia contain molecular receptors that are stimulated by odor molecules.
Jones and Reed identified a particular G protein, which they named Golf. This protein can activate an enzyme that catalyzes the synthesis of cyclic AMP (cyclic adenosine monophosphate, a nucleotide that acts as a second messenger in various biological processes), which in turn can open sodium channels and depolarize the membrane of the olfactory cell.
G proteins serve as a link between metabotropic receptors and ion channels: when a ligand binds to a metabotropic receptor (signal transduction mechanisms, often G proteins, to activate a series of intracellular events using second messenger chemicals), the G protein opens any ion channel directly or indirectly by activating the production of a second messenger. The discovery of Golf suggested that olfactory cilia contained odor receptors linked to this G protein.
Buck and Axel discovered a family of genes that encode a family of olfactory receptor proteins. In humans, it seems there are between 500 and 1000 different receptors, each sensitive to a different smell. Odor molecules bind to these receptors, and the coupled G proteins cause sodium channels to open, producing depolarizing action potentials.
Olfactory cognitive stimulation opens a field of intervention in the realm of neuroplasticity, known as the brain’s ability to recover, restructure, recompose, remodel, reform, reorganize, and adapt to new situations.
The olfactory nerves
The olfactory receptor cells send out a projection through the mucosal surface that divides into 10 to 20 cilia, which penetrate the mucus layer.
These projections gather to form the olfactory nerves that pass through the cribriform plate to reach the olfactory bulb. Approximately thirty-five bundles of axons, surrounded by glial cells, pass through small openings in the cribriform plate.
The projections terminate in the olfactory glomeruli of the olfactory bulb, where they synapse with the dendrites of mitral cells.
Two other nerve pairs accompany the olfactory nerve from the nasal cavity to the brain: the terminal nerve and the vomeronasal nerve.
The terminal nerve is formed by a bundle of thin nerve fibers that extend from the nasal septum through the cribriform plate to the lamina terminalis, entering the brain below the anterior commissure. This bundle contains numerous nerve cells and is considered a vegetative nerve.
The vomeronasal nerve, which runs from the vomeronasal organ to the accessory olfactory bulb, is developed in lower vertebrates and in humans is only demonstrable during embryonic development.
The olfactory mucosa also contains free nerve endings from the axons of the trigeminal nerve. These nerve endings mediate pain sensations that can occur when sniffing certain chemical irritants like ammonia.
The olfactory bulbs
The olfactory bulbs are thickened regions at the end of the olfactory tract that receive input from olfactory receptors. They are located at the base of the brain, at the end of the elongated olfactory tracts.
Each receptor cell sends a single axon to the olfactory bulb, where it synapses with the dendrites of mitral cells. These synapses occur in the axonal complex and the dendritic arborizations known as olfactory glomeruli.
There are approximately 10,000 glomeruli, each receiving input from a bundle of about 2,000 axons.
Nerve Pathways
Stimulus pathway
In summary, olfactory receptors consist of bipolar neurons located in the olfactory epithelium, which lines the roof of the nasal cavities, in the bone beneath the frontal lobes.
The receptors send projections through the mucosal surface, which divide into cilia. The membranes of these cilia contain receptors that detect odor molecules dissolved in the air, which reach the olfactory mucosa. The axons of the olfactory receptors pass through the cribriform plate to the olfactory bulbs, where they synapse in the glomerulus with the dendrites of mitral cells. These neurons send axons through the olfactory tracts to the brain, primarily to the amygdala (related to emotions), the piriform cortex (information processing), and the entorhinal cortex (memory, orientation, and learning). The hippocampus (learning and memory), the hypothalamus, and the orbitofrontal cortex (decision-making) receive olfactory information indirectly.
Vomeronasal organ
Most mammals have another organ that responds to environmental chemicals: the vomeronasal organ, a sensory epithelium located inside a mucous sac in the nasal septum, important in reptiles for tracking food. It also plays a key role in animal response to pheromones (chemicals produced by animals that affect reproductive physiology and behavior).
Different regions involved
The axons of the olfactory tract project directly to the amygdala and two regions of the limbic cortex: the piriform cortex and the entorhinal cortex.
- The amygdala, related to emotion, sends olfactory information to the hypothalamus, related to food intake and emotion.
- The entorhinal cortex, related to learning and memory, sends olfactory information to the hippocampus, also related to learning and memory.
- The piriform cortex, related to memory and learning, sends olfactory information to the hypothalamus and the orbitofrontal cortex, related to memory and emotion, through the dorsomedial nucleus of the thalamus, related to memory and learning.
- The orbitofrontal cortex, in addition to olfactory information, also receives gustatory information. Thus, it may be involved in the combination of taste and smell in flavors.
- The hypothalamus receives a considerable amount of olfactory information, which is likely important for the acceptance or rejection of food and for the olfactory control of reproductive processes.
Thus, through cognitive stimulation, using smell and the different odors we may encounter as a tool, we will activate brain regions related to memory, learning, emotion, decision-making, information processing… In this way, a simple activity such as recognizing different odor stimuli can result in the improvement or slowing down of various cognitive decline processes, offering us a field of intervention that can also be combined with other cognitive stimulation techniques.
Perception of specific odors
Humans can recognize over 10,000 different smells. Even if we had several hundred different olfactory receptors, or even a thousand, many odors would remain unexplained.
How can we use a relatively small number of receptors to detect so many different odors?
The recognition of a specific smell is a matter of recognizing a particular configuration of activity in the glomeruli. The task of chemical recognition becomes a task of spatial recognition.
The spatial patterns of olfactotopic information are maintained in the olfactory cortex. Likely, the brain recognizes specific odors by identifying the different activation patterns that occur.
Although most smells are produced by mixtures of many different chemicals, we identify them as belonging to a specific object, for example, the smell of coffee or the smell of cigarette smoke.
References
- N. Carlson. (2006). Physiology of Behavior. Pearson Publishing, Madrid
- W. Kahle. (2003). Atlas of Anatomy. Vol. 3. Nervous System and Sensory Organs. Omega Publishing, Barcelona
- Woo, C; Miranda, B; Sathishkumar, M; Dehkordi-Vakil, F; Yassa, M and Leon, M. (2023). Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults. Frontiers in Neuroscience.
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