Neuroanatomy: Olfaction and Taste PDF

International Medical School - NEUROAN #10 - prof. Dellavia - The mechanisms of olfaction and taste Neuroanatomy The mechanisms of olfaction and taste & correction of second assignment Prof. Dellavia - 08/11/21 - Authors and revisers: Francesco Biancole...

International Medical School - NEUROAN #10 - prof. Dellavia - The mechanisms of olfaction and taste Neuroanatomy The mechanisms of olfaction and taste & correction of second assignment Prof. Dellavia - 08/11/21 - Authors and revisers: Francesco Biancolella and Giulia Sturlese 1. Taste and taste buds Taste is a special sense located in the oropharyngeal district and taste buds are anatomical structures equipped with receptors for taste. These structures are found in different regions: the majority is located in the tongue, while a minority is spread around the access to the GI tract, between the oral cavity and the oropharynx (the section of the pharynx where the bolus passes): at the isthmus of the fauces, in the roof of soft palate. Some taste buds are also located in the glossoepiglottic valleculae, concavities in the glossoepiglottic folds that allow for the entrance of food into the oropharynx and avoid its passage into the laryngeal tract: indeed, before accessing the pharynx, the bolus comes in contact with the surface of the mucosal folds (the glossoepiglottic folds) in between the tongue and the epiglottis (one of the cartilages of the larynx). The tongue, the soft palate and the glossoepiglottic folds are innervated by three different cranial nerves: the taste reception signals, however, are conveyed to one common area in the brainstem. Tongue - dorsal surface. In the above image the epiglottis has been completely deformed in shape - indeed, its anterior portion can be seen - to close the access to the lumen of the larynx. On the dorsal surface of the oral portion of the tongue many mucosal estroflexions can be seen - these are papillae: some papillae contain taste buds, while other papillae contain other types of receptors - touch receptors, thermoreceptors and nociceptors. On the contrary, taste receptors are found in specific positions: receptors of the circumvallate papillae of the tongue are located anteriorly to the V sulcus: this V-shaped structure is easily recognizable in the picture with the foramen cecum at its vertex and the hemispherical surface 1 estroflexions of mucosa surrounding it; more peripheral to these convex extroflexions, another ring formed by extroflexions of mucosa is found. The oral portion of the tongue and its receptors, anterior to the V sulcus, are innervated by the facial nerve; the oral portion accounts for the ⅔ of the whole structure. Receptors located in the posterior region of the tongue, along the V sulcus, are innervated by the glossopharyngeal nerve; this region, representing the posterior ⅓ of the tongue, includes the circumvallate papillae and the lingual tonsils. Posteriorly, the tongue is connected to the epiglottis. Anterior to the epiglottis are two concavities: these are the glossoepiglottic valleculae, separated one from the other by a ligament, the glossoepiglottic ligament; overall, this region is involved in the swallowing reflex that ensures the closure of the access to the larynx - this will be taught in the fourth year. The glossoepiglottic valleculae host taste buds, innervated by the vagus nerve. Taste buds found at the isthmus of the fauces, in the soft palate region are partially innervated by the vagus nerve and partially, the more anterior ones, by the facial nerve. Globally from 2000 to 8000 buds can be found in a person, which results in a wide numerical variability among individuals. Taste buds, found in the papillae, contain receptors cells; in the circumvallate papillae, receptors are located on the two walls of mucosal extroflexions: this arrangement results in receptors facing the sulcus; the area is lubricated by a film of saliva secreted by glands which enhances taste perception. Foliate papillae are on the lateral margin of the oral portion of the tongue - they are extroflexions of mucosa perpendicular to the long axis of the tongue. Scattered in between, the most abundant papillae of the tongue, the filiform papillae (which are elongated and do not contain buds) there are the fungiform papillae: fewer in number, they are similar to the circumvallate in morphology however they lack the circular sulcus and the peripheral mucosal ring, thus, they are simply hemispherical extroflexions. From left to right: fungiform, foliate and circumvallate papillae. Taste buds contain both receptor cells and supportive cells; they are shaped like a calyx with small pores extroflecting in the oral cavity that capture odorant molecules, while nerve fibers reach the base of the receptor cells. In each bud 50 to 100 taste receptors can be found. 2 Location of the buds and the three nerves that innervate them 2. Taste pathways From the buds, nerves reach their ganglion in the brainstem. The facial nerve has only one sensory ganglion, the geniculate ganglion, containing both specific sensation related to taste and general somatic sensation (which comes from the few fibers collecting pain and touch information from the area inferior to the auricle, close to the exit of the facial nerve from the stylomastoid foramen). The glossopharyngeal and vagus nerves have two ganglia: one for visceral sensation and one for somatic sensation. In both cases, the ganglion for visceral sensation contains taste-related, specific sensory information. The glossopharyngeal ganglion containing taste information is called inferior or petrosal ganglion, because it is located below the petrous portion of the temporal bone; the other ganglion of the glossopharyngeal nerve is more superior. The ganglia of the vagus nerve are the inferior or nodose ganglion (which contains sensory information) and the superior ganglion. After reaching their respective ganglia, fibers carrying taste information continue the course, converging into the nucleus of the solitary tract. The solitary tract vehicles information to the thalamus, particularly to an area dedicated to taste in the ventral posteromedial (VPM) thalamic nucleus (both the trigeminal and the solitary tract reach the VPM). Taste sensory information reaches the postcentral gyrus, as the main sensation, but it also reaches the frontal operculum and the insular region. 3 From the thalamus taste sensation reaches the highlighted areas of the telencephalon, including the postcentral gyrus and, in particular, an area dedicated to taste in its lower, lateral-most aspect, very close to the sylvian fissure. Deep to this area, the insular cortex has area 43 dedicated to taste. 3. Olfaction and olfactory mucosa Human beings, being microsmatic, have less levels of olfactory function with respect to other animals, and have a genome in which only about 2% of the DNA is dedicated to olfaction-related proteins. In spite of this, many areas in humans are dedicated to olfaction. All receptors for olfaction are located in a small area in the nasal cavity: mainly in the roof, but partially also on the superior portion of the lateral walls; essentially, receptors are located in the region of respiratory mucosa lining the upper nasal concha, in the most superior turbinate of the ethmoid bone. This area is close to the cribriform plate of the ethmoid bone, a porous structure that allows for the entrance of fibers of the olfactory nerve into the anterior cranial fossa. Olfactory mucosa is also found at the beginning of the perpendicular plate of the ethmoid bone. Location of olfactory mucosa. Receptor cells are alternated to supportive cells; in addition, there are some deep-located basal cells, found very close to the bone and olfactory glands that release their content towards the mucosa - like in taste, even in olfaction, a film of glandular secretions enhances perception. 4  4. Organization of olfactory mucosa Olfactory cells are primary receptor cells, thus they are neurons; they have hairs containing receptor proteins: each hair has a specific protein that binds to one specific odorant molecule, allowing a wide spectrum of odorant reception. The glands secrete fluids that allow to solve the odor molecules, for a better reception. Basal cells surround the portion of olfactory cells in proximity to the cribriform plate; being precurosors, they substitute damaged receptor cells. Receptor cells have a central process that continues through the cribriform plate, surrounded by schwann cells to form the fibers of the olfactory nerve. They also have a portion facing the lumen of the olfactory cavity: it is enlarged on the surface, with the olfactory vesicle containing receptor proteins for specific odors: hair extroflexions protrude from this area - they are properly microvils capturing olfactory information directly into the lumen of the nasal cavity. Alternated to the receptors are the supportive cells and the ducts of the bowman’s glands. Detailed organization of olfactory mucosa. 5  5. Olfactory bulb When the central processes reach the anterior cranial fossa, surrounded by schwann cells, they continue into the olfactory bulb, a structure dedicated to olfaction. The olfactory bulb is part of the telencephalon: indeed, nerve fibers related to olfaction directly reach the telencephalon: they don’t go through the brainstem nor have an obligated station in the thalamus; however, some of their collaterals can reach the thalamus. The olfactory bulb, thus, is a structure belonging to the supraxial organs. It is located against the floor of the anterior cranial fossa, just over the horizontal portion of the squama of the frontal bone, below the orbital area. Location and internal structure of the olfactory bulb. The olfactory bulb is made up of three cell types: the mitral cells, the tufted cells and the granular cells; cells are arranged in different layers of the stratified olfactory bulb. Mitral cells are located in a very deep layer of the olfactory bulb and olfactory nerve fibers can synapse with these cells in the glomerulus (a sort of plexus). Another type of cells are the tufted cells. At the glomerular layer, which is more external, both these cells have their terminals. Tufted cells are immediately deep to the glomerular layer while mitral cells are even more deep. The innermost layer of the bulb is made by granular cells. The afferent olfactory fibers synapse at the level of the glomerulus with the mitral and with the tufted cells and continue the transmission of the signal for further elaboration and integration. Mitral cells are highly discriminative and finely differentiate between odors. Tufted cells maintain a similarity between odors and allow the linkage of odorant molecules that share some aspects, building up a recognizable information of smell: they have an associative role. Granular cells can be found both in the deep inner layer, while also alternated to glomeruli. These cells receive the signal from efferent olfactory fibers and are involved in higher centers’ modulation, acting at the level of the glomerulus. They play a role in lateral inhibition and in signal-sharpening. 6. Medial and longitudinal olfactory striae From the olfactory bulb, afferent fibers (mainly from mitral and tufted cells) continue into the olfactory tract, which is reduced in size with respect to the bulb. This tract has the possibility to host nuclei, and in the initial portion, close to the base of the bulb, it hosts the anterior olfactory nucleus. From the anterior olfactory nucleus efferent fibers reach the bulb and synapse with granular cells, in order to have lateral inhibition. The tract moves from anterior to posterior and reaches an area in the anterior cranial fossa where it divides into different striae: medial, intermediate and lateral striae. Most of the fibers enter the lateral stria. The point where fibers divide is called olfactory trigonus, 6 and is in proximity of the optic chiasm. It is thanks to the medial striae that information from both sides can enter in communication. This happens through the anterior commissure, on the midline. This pathway is used to allow fibers from the medial stria to synapse with efferent fibers in the anterior olfactory nucleus of the contralateral side. Fibers from the lateral and intermediate striae go ipsilateral to reach the primary areas in the cortex dedicated to olfaction. The primary olfactory cortex is also called piriform area and it is subdivided in two subareas: the uncus and the perforated substance. The piriform area is located in the frontal, temporal, insular and limbic lobes. Notice the piriform area (in light pink on the left), which includes the anterior perforated substance and the uncus. The intermediate stria is not reported in the picture on the right. 7. Olfactory pathways At the level of the trigonus a group of cells forms a nucleus: the tubercle. Fibers arriving to the olfactory tubercle, found in between lateral and medial striae, synapse and project to the dorsomedial nucleus of thalamus. From this nucleus of the thalamus fibers project to the orbitofrontal cortex, where there are areas important for the creation of personality, thus information used for relations with other individuals. This picture shows the olfactory pathways from another angulation. 7 The primary sensory areas for olfaction are the piriform cortex, periamygdaloid (surrounding the amygdala) and the pre-piriform areas (in the frontal lobe). Going posteriorly and medially there are secondary areas for olfaction, represented by the entorhinal area (area 28 of Brodmann) and by the parahippocampal gyrus (limbic lobe). These areas receive information from the primary areas and are important since olfactory information is used in different associative areas. 8. Principal connections of the olfactory system Observing the following picture: Information from the nasal mucosa arrives in the olfactory bulb, from which afferent fibers can project into the primary olfactory cortex (red lines in the pic below). Fibers can enter into the anterior olfactory nucleus, and in the olfactory tubercle (red lines in the pic below). From the piriform cortex fibers can go in the amygdaloid body (areas surrounding the amygdala) and in the entorhinal cortex (green lines in pic below). To reach the thalamus, fibers of the intermediate stria have to go to the olfactory tubercle first, and from there they will go in the thalamus (light blue lines in pic below). The thalamus also receives information from the piriform cortex and hippocampus. Besides receiving fibers from the thalamus, the orbito-frontal cortex can receive fibers from the piriform cortex. Hippocampus and amygdala are part of the limbic system, putting it in connection with the olfactory system. The hypothalamus can receive from the amygdaloid body and the entorhinal cortex. Efferent fibers (dark blue in pick below) come mainly from the anterior olfactory nucleus and piriform cortex, back to the olfactory bulb. 8 The olfactory and taste pathways share a connection to the insular lobe to establish functional interaction. Amygdala and hypothalamus are also involved to connect emotional and autonomic responses to these sensations. In particular the hypothalamus is involved in the control of autonomic responses, starting from olfactory information. As already mentioned, from the olfactory bulb three striae originate: the lateral one is the main one since it goes directly to the primary (piriform) olfactory cortex. From here fibers can go in the entorhinal cortex, and from this cortex, with the perforating pathway they can reach the hippocampus which is part of the limbic system. In a parallel way fibers from the lateral stria can also go in the amygdala and from here (with the terminal stria) enter parts of the limbic system which are in the brainstem, like the reticular formation. These are the main routes of the lateral olfactory stria. The main route of the intermediate stria is the one that involves thalamus and orbitofrontal cortex, as already described. Collaterals of the main route can enter the anterior perforated substance (belonging to the primary olfactory cortex), the hypothalamus and the piriform cortex. The main route of the medial stria is the one that involves the anterior commissure and the contralateral olfactory bulb and efferent fibers, as already described. Entering the anterior commissure, thus all the white matter connections in between the two hemispheres, fibers from the medial stria are able to synapse also with the septal nuclei (part of the limbic system), located in the septum pellucidum (another part of the white matter in between the two hemispheres) for information integration. This part will be analyzed better in the lecture on basal ganglia. 9 10  9. Correction of the second assignment - Solitary tract Notice how the special visceral afferents related to taste are in red and the general visceral afferents are in blue. In the cross section notice that general afferents are located more medially (in blue) and taste afferents are located more laterally (in red). 11 The nucleus of the solitary tract (solitary nucleus), is a very big nucleus located mainly in the medulla oblongata. Fibers from three cranial nerves, glossopharyngeal (IX), vagus (X) and facial (VII) arrive at this nucleus. Each cranial nerve has its own ganglion and each cranial nerve vehicles in these ganglia general visceral sensory information and taste information. The ganglion of the vagus (also called nodosum), as the inferior ganglion of the IX nerve and the geniculate ganglion contains the cell bodies of both special and general visceral afferents. From taste buds fibers arrive in the most cranial part of the solitary nucleus; this area is also called ala cinerea. The general afferents instead arrive in the inferior-most part of the solitary nucleus and vehicle information from: - aortic body, information relative to pressure, partial pressure of oxygen and carbon dioxide - abdominal and thoracic viscera - laryngeal and pharyngeal mucosa - soft palate and epiglottis (gustatory) In the ganglion of the glossopharyngeal nerve (also called petrous ganglion), information arrives from: - the pharyngeal mucosa - the carotid body, to allow the modulation of the pressure and chemical parameters inside the internal carotid artery. - parotid gland - palatine tonsilla - posterior third of the tongue, both gustatory and general sensory In the ganglion of the facial nerve (also called geniculate ganglion), information arrive from: - submandibular gland - sublingual gland - lacrimal gland - anterior two thirds of the tongue (gustatory) General visceral afferents related to respiration and circulation also arrive in the solitary nucleus. Indeed, at the level of the medulla there is a central pattern generator of complex functions, that are organized at this level and can be modulated thanks to information from these general visceral afferents. Central pattern generators (CPGs) are generally defined as networks of neurons capable of enabling the production of central commands, specifically controlling stereotyped, rhythmic motor behaviors. Several CPGs localized in brainstem and spinal cord areas have been shown to underlie the expression of complex behaviors such as deglutition, mastication, respiration, defecation, micturition, ejaculation, and locomotion (this part in italics was taken from the abstract of the article https://pubmed.ncbi.nlm.nih.gov/30543520/). These complex functions are vehiculated to thoracic and abdominal viscera mainly by the vagus nerve, but also by the glossopharyngeal nerve. Thus the laryngeal mucosa is innervated completely by the vagus, the pharyngeal mucosa is innervated by a plexus that is made up by both vagus and glossopharyngeal nerves. Somatosensory information also passes in the ganglion of the facial nerve, even if somatosensory information doesn’t go in the solitary nucleus. Somatosensory fibers of the XII, X and IX cranial nerves go in the trigeminal nucleus, and somatosensory fibers of the X and IX cranial nerves do not pass in the nuclei shown in the picture above. From the solitary nucleus visceral fibers ascend in the solitary tract, mainly ipsilaterally and can have synapses in the parabrachial nucleus. The parabrachial nucleus is just a modulation station for fibers before reaching the amygdala, which is a final destination. The final destination of visceral fibers that 12 do not synapse in the parabrachial nucleus, is the hypothalamus. Thus general visceral afferents go to the limbic system in any case. These fibers are organized in a pretty different way with respect to the somatosensory ones that ascend mainly contralaterally and in the head and neck completely bilaterally. Considering the afferents transferring information related to taste, from the solitary nucleus they synapse with nuclei located in the brainstem, like the salivatory nucleus and the hypoglossal one, this is true for fibers belonging to all of the three cranial nerves. Synapses with the salivatory nucleus are important to modulate the flux and the content of saliva in response to taste information. The connection with the hypoglossal nucleus is important for the modification of the shape of the tongue, this happens during mastication and swallowing. Fibers also ascend to the VPM of the thalamus, the same nucleus used by the trigeminal nerve, allowing the convergence of taste and somatosensory information. From the thalamus fibers reach to the primary somatosensory cortex, in the postcentral gyrus in an area specific for the elaboration of taste information. Collaterals can also go from the thalamus, in the insular lobe to have association of taste information with other kinds of information. To note, the pathway for taste is completely ipsilateral. 10. Vestibular system 13 From the receptors in the ampullae of the semicircular canals and in the maculae, fibers reach the nuclei of the vestibular system or the cerebellum directly; all the cells have proto-neurons in the vestibular ganglion (also called scarpa’s ganglion); from the vestibular ganglion, the pathway continues. The direct access to the cerebellum is depicted in green; from the cerebellum, fibers reaching the nuclei of the vestibular apparatus can rise as well. The vestibular apparatus has four nuclei, superior, inferior, lateral and medial - the different nuclei receive different branches of the vestibular nerve. From the superior and lateral nuclei, with the participation of the other two, an ascending pathway is created forming the medial longitudinal fasciculus. From this fasciculus, there can be connections with motor nuclei of cranial nerves, such as those of the oculomotor nerve. Fibers can reach the superior and inferior (S or I) VPM; from there, they reach the primary somatosensory cortex, where conscious elaboration of the information provided by the vestibular system occurs. Using the medial longitudinal fasciculus, descension is possible. In the descending aspect of the medial longitudinal fasciculus, information coming from the medial vestibular nucleus can be collected forming the medial vestibulo-spinal tract, which ends at mid-thoracic level. The medial longitudinal fasciculus (ascending and descending) is posterior to the spinal and medial lemniscus. Descension is bilateral though mainly ipsilateral. Descension can also occur via the lateral vestibulo-spinal tract; in this case descension is completely ipsilateral. The lateral vestibulo-spinal tract is longer, reaching the sacral neuromeres. All four vestibular nuclei can project to the cerebellum and receive info from the cerebellum. These nuclei are quite lateral in the brainstem, coherently with belonging to the special sensitivity. 14  11. Acoustic system There are two cochlear nuclei: dorsal and ventral. They both receive information from the spiral ganglion, coming from the Corti organ. From the two nuclei, three striae can rise: anterior, intermediate and dorsal. From the ventral cochlear nucleus, the ventral stria originates and synapses in the nuclei of the trapezoid body. Some of the fibers ascend ipsilaterally, but the majority ascends contralaterally; immediately over the trapezoid body they synapse at the superior olivary nucleus, which is a site of decussation. At this level, a lateral lemniscus with several nuclei is created. Just one of the nuclei of this pathway is depicted in the image. From the lateral lemniscus, ascension continues 15 reaching the inferior colliculus of the lamina quadrigemina: from there, fibers project to the thalamus into the medial geniculate body. From the medial geniculate body, they reach the temporal gyrus in the primary acoustic cortex. Signals between the two sides are continuously exchanged, even at the level of the inferior colliculus, thanks to commissures. Another option from the superior olivary nucleus is the rise of efferent fibers. The intermediate and dorsal striae are posterior to the trapezoid body; fibers are mainly contralateral and can synapse in the reticular formation before reaching the lateral lemniscus. 12. Optic pathways 16 In red fibers coming from the lateral retina and in blue the ones coming from the medial retina. The fibers coming from the retina decussate partially at the level of the optic chiasm - the decussating fibers that decussate are those coming from the medial part of the retina, thus collecting information from the lateral aspects of the visual fields. On the other hand, fibers from the lateral part of the retina remain ipsilateral. Most of the fibers from the retina enter the medial geniculate body. In the picture the alternance of the layers and fibers coming from either the lateral or medial retina are reported. The first two layers are related to the magnocellular system, while the rest of the layers are related to the parvocellular system. Part of the fibers can escape the lateral geniculate body and go either to the superior colliculus or to other nuclei of the pretectal formation; from here, reflexes can be created. Fibers from the lateral geniculate nucleus will form the optic radiations and go to cortical areas: primary visual cortex at the level of the calcarine fissure (area 17), from here there are connections with secondary visual cortex (areas 18 and 19). 17 13. Pupillary reflex 18 Fibers from the retina go around the medial geniculate nucleus into the superior colliculus, also contralaterally, since the two superior colliculi are connected by the posterior commissure (this way simultaneous activation of the reflex can happen). From the superior colliculus fibers go in the area of the oculomotor nucleus: for the somatic reflex the somatic oculomotor nucleus will be used, for the visceral reflex the Edinger-Westphal nucleus will be used. From here information from the two sides can be integrated using other nuclei, and then using the fibers of the oculomotor nerve information will reach the superior orbital fissure. After exiting the superior orbital fissure the ciliary ganglion will be reached. From the ciliary ganglion it is the trigeminal nerve, ophthalmic division, nasociliary branch, that will collect fibers and innervate two muscles: the sphincter of the pupil and the ciliary muscle. The trigeminal nerve regards the parasympathetic innervation, thus for accommodation of the eye and pupillary miosis. For sympathetic innervation: at the level of the middle cranial fossa, when the oculomotor nerve has to pass through the superior orbital fissure, it collects sympathetic fibers from nerves that are part of the plexus around the carotid artery. These fibers that arrive to the oculomotor nerve thanks to the carotid artery derive from the superior cervical ganglion of the sympathetic chain. Afterwards the oculomotor vehicles sympathetic and parasympathetic information together in a parallel way. Sympathetic fibers do not need to synapse in the ciliary ganglion since they are already postganglionic, arriving from the superior cervical ganglion of the sympathetic chain. These fibers will cause mydriasis of the pupil under specific conditions. 19