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Introduction
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What’s up! Taim Talks Med here, let’s start with our Cranial nerve series.
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Cranial nerves are twelve pairs of nerves that exit the brain and the brainstem,
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and in this segment, we’ll talk detailed about the first cranial nerve, which is the Olfactory nerve.
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And we’ll do that by first making a quick scheme of the olfactory pathway to get an overview of it.
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Then we’ll talk detailed about the Olfactory epithelium and nerve. Basically which striuctures
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are involved in sensing particles of smell. Then we’ll follow the olfactory pathway and
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look at which structures in the brain are involved when you smell something.
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And after that, we’ll do some clinical relevance and examples of conditions that can alter the
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normal functioning of this nerve. So, the olfactory nerve conducts
Olfactory Nerve Scheme
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the sensation of smell to the brain via the olfactory bulb and tract.
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Let’s visualize this sentence. Here we got a funky smell of some sort, let’s say someone opened a box
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of tuna next to you, or maybe someone farted. These gaseous odorants will eventually reach
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your olfactory nerves. Axons of these olfactory nerves are gonne come together, and run through
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the cribriform plate, of the ethmoidal bone. So we call the olfactory nerve a 1st order neuron
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because this is where smell is first registered. Once they go through the cribriform plate,
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they will synapse with neurons in the olfactory bulb. The olfactory bulb is an elongated structure
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that lies just above the cribriform plate. It continues posteriorly with the olfactory tract.
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As the olfactory tract approaches the anterior surface of the midbrain, it becomes wide, now
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called olfactory trigone. Located just in front of the anterior perforated substance. The olfactory
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trigone now divides into striae. It divides into the medial stria, the lateral stria, and in some
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cases the intermediate stria, which extend into the anterior perforated substance and ends in a
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slight elevation called the olfactory tubercle. The lateral stria terminates in the primary
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olfactory cortex of the temporal lobe and we’ll talk about that in details when we get to it.
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The medial stria passes to the contralateral olfactory tract and terminates in the limbic
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structures to contribute to the emotional responses brought on by the smell.
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Alright so that is the general outline. Let’s now cover this pathway in a little detail,
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starting from the nasal cavity and then follow the pathway to understand the mechanism behind smell.
Olfactory Nerve and Epithelium
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So here we see the nasal cavity, along with the pharynx, oral cavity and the hard and soft palate.
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The sense of smell begins in a small area on the roof of the nasal cavity. They’re
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a specialized collection of cells that lines the upper part of the nasal cavity in humans.
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Let’s take a section of that specific region and look detailed into the
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structures that are responsible for helping with the sense of smell.
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The olfactory part of the nasal cavity consists mainly of what is called olfactory epithelium.
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The olfactory epithelium consists mainly of what is called pseudostratified columnar epithelium and
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it lies on top of a lamina propria. The cells that make up the olfactory epithelium are Basal cells,
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that act as stem cells and can differentiate into olfactory epithelium. We have Sustentacular cells,
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which support the olfactory neuron function. We got an olfactory gland cell, or bowmans gland,
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which produces mucin. Then we got olfactory receptor neurons. These neurons are formed as
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a bipolar neuron remember is a type of neuron that has two extensions , one dendrite that
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contains nonmotile sensory cilia going to the epithelial surface, and one axon going upwards
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that transmits signals to the olfactory bulb after crossing the cribriform plate.
How Do We Detect Smells?
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So what happens is, when we inhale, we create a turbulent airflow whichn the the nasal cavity.
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Odorants has two ways of coming in. One way is through the nasal opening, and another way of
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detecting smell is through posterior transfer of odorants from the nasopharynx, which is important
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for the detection of flavor during eating and drinking. Remember taste is 80% dependent on
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olfaction, so without the ability to smell, all food and drink can only be sensed as one of those
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five basic tastes, with no other differentiation possible. So odorant comes in, what happens?
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you know one of the most important things about the nasal cavity is that there’s a lot of mucus.
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There’s a lot of mucus in this area. And the purpose of mucus is important because not only
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is it good in basically helping to humidify the incoming air, moisen the incoming air,
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warming the incoming air, but also certain particles. So certain particles will enter the
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nasal cavity and diffuse into the mucus. They then bind to certain proteins and gets transported to a
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sensory cilia of the olfactory dendrite. Remember cilia has specific olfactory receptors on them.
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Each receptor is capable of binding to several different odorants — some more
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tightly than others. Each odorant is capable of binding to several different receptors. This
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provides the basis for combinatorial diversity. So Odorant A binds to receptors on neurons #3,
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#427, and #886. Odorant B binds to receptors on neurons #2, #427, and #743. And the brain
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then would interpret the two different patterns of impulses as separate odors.
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This mechanism allows us humans to be capable of discriminating between a trillion different
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mixtures of odorants. Dogs can detect up to 1000 to 10000 times more odorants than us.
Mechanism of Odorant Signal Transduction
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So what happens is, an odorant bind to a transmembrane protein, a “7-pass” transmembrane
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proteins we call it, since it passes through the membrane 7 times. And it’s bound to a G protein,
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so it’s a G protein-coupled receptor. So an odorant binds to a G-coupled receptor
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and activates a G-protein. The activated G-protein gets rid of GDP and binds to a GTP,
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that then activated an adenylyl cyclace which catalyzes the conversion of ATP to the “second
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messenger” cyclic AMP. And when the concentration of cyclic AMP increases within the olfactory cell,
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it binds and opens ion channels. Now we get an influx of positive sodium
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and calcium ions and an efflux of negative chloride ions. This neuronal depolarization
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continues until the threshold potentially occurs, firing a resulting action potential.
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So the odorant has to be strong enough toinducee an action potential in order for us to smell it.
Olfactory Nerve
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Now the cilia is stimulated and pass the signals up via
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the dendrite and the cell body to the axon on the olfactory sensory neuron.
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Axons from the olfactory neurons form nerve bundles, or fila olfactoria. Many of these
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bundles combine to create the olfactory nerve, which is enclosed by dura and arachnoid mater.
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The olfactory nerve is the shortest fot he 12 cranial nerves, and is unique in that it can
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partially regenerate. Which is good because olfactory neurons are lost with exposure to
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environmental toxins, and inflammation. But they’re also said to be lost with age aswell.
Olfactory Bulb
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Now as the axons pass through the cribriform plate of the ethmoidal bone, they enter into
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what’s called the olfactory bulb. Now in the olfactory bulb, they will synapse with special
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cells called mitral cells. And this synapse between the olfactory and the mitral cells
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is called glomeruli. SO they form glomeruli between the axonal and dendritic branches.
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Signals are passed through the mitral cells, and it’s the mitral cells that carries information
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of individual odors back to the brain. But we can find other cells here in the olfactory bulb too.
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There are Tufted cells, which are a minor version of mitral cells. They’re different
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than mitral cells in that they’re smaller, they connect to several glomeruli whereas mitral cells
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only connect to one glomeruli. And they’re many more. We got more tufted cells and mitral cells.
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Other cells that we can find here too are amacrine granule cells, which are inhibitory interneurons,
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allowing only the most excitatory impulses to stimulate the mitral cells. So many impulses
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come in, only the most excited ones are allowed by the granule cells to stimulate
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the mitral cells. We got also periglomerular cells that are thought to do the same as
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amacrine granular cells. So they function by dampening the excitation of mitral cells.
Olfactory Pathway
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So, axons from mitral and tufted cells leave the olfactory bulb through the olfactory tract.
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The tract passes underneath the medial fronal lobe inside the olfactory groove. And then as the tract
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gets close to the anterior perforated substance of the midbrain, it becomes flatter and widens
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as the olfactory trigone. From the olfactory trigone, the tract is gonna continue as stria.
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Three olfactory striae. There’s the lateral olfactory striae, medial olfactory striae and
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the intermediate olfactory striae. Cranial nerve 1 is one of two cranial nerve that doesn’t directly
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enter the brainstem, the other is the optic nerve. Let’s follow the lateral striae here for a minute.
Lateral Olfactory Stria
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The lateral stria continues on to an area deep in the temporal lobe called uncus,
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which is the anterior portion of the medial parahippocampal gyrus. From here, information
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are sent to the primary olfactory cortex. Now what the heck is the primary olfactory cortex?
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The term olfactory cortex is applied to all areas of the cerebral cortex that receive
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direct fibres from the olfactory bulb. Kinda makes sense doesn’t it?
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In the past it has been held that olfactory pathways differ from other sensations in
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that there is no relay in the thalamus. Usually when you study the nervous system,
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you see that all the sensory pathways usually sends fibers through the thalamus. It has long
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been said that the olfactory pathways differ in that there’s no information sent to the thalamus.
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This concept has now been changed in that while most olfactory fibres
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reach their cortical targets, some fibers are now believed to reach the thalamus.
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And because we now understand a little more of the olfactory cortex than we used to,
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we now divide the oflactory cortex into primary and secondary cortical projections.
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Primary olfactory projections are the areas that first receive the information directly
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from the olfactory bulb. And the main regions receiving direct fibres from the
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olfactory bulb are a whole lot of areas, we got the piriform cortex, the semilunar gyrus,
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the anterior part of the entorhinal area. You don’t really need to know where these are located
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specifically unless you’re researching about them. But what’s good to know is that from here,
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fibers are sent to what’s called the secondary olfactory areas. Or secondary olfactory cortex.
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Fibers are gonna go to an area called the entorhinal area, or brodmann area
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28. It’s partly considered a part of primary olfactory cortex aswell because remember,
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the anterior part of the entorhinal area receives a few fibres directly
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from lateral olfactory stria. But the posterior part of entorhinal area is
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secondary olfactory cortex because it receives fibres from primary olfactory
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cortex. The entorhinal cortex is concerned with processing information about odours.
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From the entorhinal area, information are sent to the amygdala which is associated with the emotion
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of fear associated with smell. And from the amygdala, fibers are sent to the hippocampus.
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And since fibers go to the hippocampus, then you’re going to process the smell and form new
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memory. Hippocampus is associated with memory. Another place that the olfactory cortex is
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gonna send odor information out to are portions of the hypothalamus and brainstem
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that trigger autonomic responses involved in appetite, salivation, and gastric contraction.
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Another place that’s gonna be involved in all of this is the oribitofrontal cortex.
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Fibers are going to go from the primary olfactory cortex to the medial dorsal
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nucleus of the thalamus, and then to the orbitofrontal cortex. The orbitofrontal
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cortex is also secondary olfactory cortex. It provides conscious perception of smell. It helps
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you consciously understand what you’re smelling. So you see whenever you smell something,
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through the primary olfactory cortex we gain the ability to discriminate between odors,
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we can process complex odorant mixtures. Odors take a direct route to the limbic system,
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including the amygdala and the hippocampus, the regions related to emotion, memory and reward.
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You’re consciously aware of the smells through the orbitofrontal cortex. You know.. the olfactory
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sensation has a very interesting pathway. So all of those parts of the brain are
Medial Olfactory Stria
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involved because of the lateral olfactory striae. The medial olfactory striae are actually gonna
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move around what’s called the paraolfactory area, and it’s gonna go to a specific gyrus here called
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the sub-colossal gyrus. The subcallosal gyrus is also considered a part of limbic system of brain,
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so the reward system, emotions, memory and all of those things.
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Now, we talked about the lateral olfactory stria and the medial olfactory stria. Between them, the
Intermediate Olfactory Stria
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intermediate olfactory striae it goes out towards the anterior perforated substance of the midbrain
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region, and ends as the olfactory tubercle. The olfactory tubercle is a sensory processing centre,
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it received input from olfactory bulb and also from the amygdala and it’s believed to also play
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a role in the reward system. It identifies rewarded odors, and based on that you know
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it affects your behaviour and decisions. So the reward system represents behavioral responses.
Anosmia and Dysosmia
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One thing that’s also important is that some of these fibers can cross to the
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other side. So smell can be bilateral, even though most fibers are ipsilateral,
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some fibers do cross. So smell is bilateral. So up until now we talked about the olfactory
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pathway, we talked about where it’s going to in the cerebral cortex. Now I wanna say
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what can happen if it’s not funcitonin correctly. Anosmia, is when you temporarily or permanently
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lose the ability to smell. And there’re a lot of conditions that can cause this. One of the
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most common cause of anosmia is some type of inflammation, or infections. Imagine if
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there’re any sort of inflammation I this area. Any type of situation like that, a lot fo mucus
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builds up. Now the odor molecules has to travel a farther distance, they have to be dissolved a
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farther amount. Now there’re less molecules that reach the olfactory receptors. You know what else
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is important remember I told you that smell is directly related with taste? If you ever
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been really clogged, and have a nasal infection a sinus infection. You probably also noticed that
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your taste of food is also not very great, right? That’s’ because a lot fot hese information from
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the olfactory neurons are gonna be intertwined with the cerebral cortex in certain taste centers.
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Infalmmation can also damage supporting cells and the actual olfactory dendrites which can
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also cause anosmia. Blocking of the nasal passage can cause anosmia. Trauma of the orbit or the
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nasal cavity can cause anosmia, damaging the ethmoidal bone, the cribriform plate of the
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etmoidal bone. If there’s a pathological lesion in the brain of any of those pathway we talked about,
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that can alter the perception of smell. Also, if there’s a degenerative CNS disease,
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that can damage the neurons that take impulses towards the brain, reducing the amount of smell.
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Then we got something called Dysosmia. Dysosmia is when you can smell,
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but the smell perception is distorted. Where some familiar objects may smell different or
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unpleasant to you. They can further be divided into Parosmia, where normal smell now taste or
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smell unpleasant or disgusting. And Phantosmia, where you detect smells that aren’t really
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there in your environment. Terrible condiciton. Parosmia are usually caused by chronic conditions,
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so chronic nasal congestion, chronic sinusistis or prior head traumas can
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also contribute to this. You know any damage to olfactory nerve fibers can
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occur as a complication of upper respiratory tract infections. And in some cases a decrease
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in the number of nerve fibers from these infections mean that there are not enough
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different fibers to accurately differentiate odors, which you know result in parosmia
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Phantosmia has been shown in people with inflames sinuses aswell, but there are some medications
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that can trigger olfactory hallucination, specially some types of antipsychotics,
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antimigraine medicine, and antiseizure drugs aswell. Brain tumors can cause olfactory
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hallusinations aswell depending on where the lesion is. In some cases that can be a clinical
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sign of a tumor whithin the CNS. Alright now a quick recap.
Recap
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There’s a smell in your environment. These gaseous odorants will eventually reach your….
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olfactory nerves. Axons of these olfactory nerves are gonne come together,
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and run through the cribriform plate, of the ethmoidal bone. So we call the
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olfactory nerve a 1st order neuron because this is where smell is first registered.
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Once they go through the cribriform plate, they will synapse with neurons in the …. olfactory
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bulb. The olfactory continues posteriorly with the olfactory tract. As the olfactory tract
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approaches the anterior perforated substance, it becomes wide, now called olfactory trigone.
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The olfactory trigone now divides into striae. How many stria does the olfactory trigone divide into?
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Three striae, those are the medial stria, the lateral stria, and in most cases the
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intermediate stria. The lateral stria terminates in the primary olfactory cortex of the temporal
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lobe. The lateral olfactory stria contains the largest number of fibers in the olfactory
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tract and is responsible for the majority of functional olfactory transmission. So it enter
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the temporal lobe near the uncus, where the primary olfactory cortex is. The medial stria
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passes to the contralateral olfactory tract and terminates in the limbic structures to
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contribute to the emotional responses brought on by the smell. The intermediate stria extend into
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the anterior perforated substance and ends in a slight elevation called the olfactory tubercle,
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which plays a part in the reward system. So that was everything I had for the first
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cranial nerve. The next video is going to be about the second cranial nerve, the Optic Nerve.
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Alright guys so that pretty much covers the Olfactory nerve. Thank you so much for watching
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another one of my videos. If you enjoyed, learned something from it, please remember to like,
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