NEUROAN #2 - 11.10.21 - Ascending Pathways PDF

International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways ANATOMY #2 Ascending Pathways Prof. Della Via– 11/10/21 – Author: Mark Hage Assaf – Reviser: Veronica M...

International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways ANATOMY #2 Ascending Pathways Prof. Della Via– 11/10/21 – Author: Mark Hage Assaf – Reviser: Veronica Mazzoleni 1. White matter The white matter is composed by ascending fibers located in the three columns of the spinal cord which are the anterior, lateral and posterior; the descending and ascending intersegmental systems made of funicular fibers which are located at the periphery of the grey matter in the perigriseum (small area that surrounds the grey matter); and descending fibers which have projections in the anterior and lateral columns. Therefore, the posterior column is only dedicated to the sensory fibers. 2. Ascending pathways: general somatic - Somatosensory pathways to consciousness: 1. Medial division: posterior column- medial lemniscus – primary somatosensory cortex. 2. Lateral division: anterolateral system- spinal lemniscus- primary somatosensory cortex. - Somatosensory pathways to unconsciousness: 1. Lateral division: anterolateral column- spinocerebellar tract – cerebellum 3. Medial division The medial division is located into the dorsal column of the spinal cord. It is made of two fasciculi: the fasciculus gracilis and cuneatus. They do not synapse at the level of the grey matter, so they enter in the posterior horn of the white matter and continue their course as first order neurons. There are few fibers (max 10%) that are exceptions and synapse at the dorsal horn those fibers are collateral to the main fasciculi. Moreover, there are some collateral fibers that travel into the intersegmental tract. 1 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways Fasciculus gracilis and cuneatus pathway: The receptors of this pathways can be exteroceptors such as Meissner’s and Pacinian corpuscles or proprioceptors as muscles spindles and tendon organs. At the level of the neuromere the first order neuron enters in the funiculi following a precise somatotopism (cranial - caudal, lateral - medial). The fibers will ascend until the nuclei gracilis and cuneatus present in the medulla where they synapse. At this level the fibers decussate and will travel contralateral (opposite side from where they originate) until they reach the thalamus where they synapse in the VPL (ventral posterolateral) thalamic nuclei. The final target is the primary somatosensory cortex, which is located at the posterior central gyrus, in the parietal lobe. Fasciculus cuneate is formed by all the fibers that are entering from the neck until mid-thorax, below this level the fibers will form the funiculus gracilis. Therefore, the fasciculus gracilis is composed by fibers from the caudal aspect of our body, while the fasciculus cuneatus is formed by more cranial fibers. The somatotopism at the level of the dorsal column of the dorsal funiculus is cranial- caudal, lateral- medial: the more cranial information is located laterally while caudal fibers correspond to medial position in the fasciculi. Somatotopism is important because when there is a lesion it’s possible to know what the damage is. The somatotopism changes throughout the path. 2 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways (Spinal cord level) The information coming from the receptors have a specific somatotopism as well: more ventral there are the neurons conveying information of fine touch, able to discriminate with precision what is being touched (cotton and silk for example). Ventro-dorsally fine touch, position, movement, vibration and pressure. At the level of the brain stem, where the neurons synapse at the nuclei gracilis and cuneatus, arrive also the stimuli of fine touch and proprioception from the head and neck collected by the trigeminal nerve. The trigeminal nerve is the major nerve that dives proprioceptive information of the face, for sure of the masticatory muscles but for the rest of them it is not well understood yet how proprioception. In this case following the somatotopism the nerves arriving from the trigeminal nerve will be more lateral. (medulla) At the level of the medulla, below the fourth ventricle, there are the nuclei which are dorsal. Immediately after the synapse the neurons decussate. The axons of the second order neuron move anterior to the ventricle, creating internal arcuate fibers forming the medial lemniscus. The medial lemniscus is positioned immediately posterior to the pyramids which are the descending system positioned ventrally in the medulla. In the image (in red) is possible to see the topographic disposition of the fibers in the medial lemniscus at the level of the medulla: cranio-caudal, postero-anterior. From now on the information will be conveyed contralaterally. 3 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways (pons) At the level of the pons ventrally there are the basilar nuclei of the pons and the fascia of the pons made by fibers that are organized transversally creating the correlation system. Posterior to the fascia there’s the medial lemniscus (in red). Here the rotation of the fibers is completed (rotation of 90°), so the fibers are running in the opposite side with respect to the beginning. Therefore, the somatotopism has changed: cranio-caudal, medio-lateral. The fibers will ascend in this way to the brain stem. (Midbrain) In the midbrain there is a very small rotation of the medial lemniscus. More ventrally there are the cerebral peduncles, while posteriorly there are the red nuclei and substantia nigra. Medially there are the periaqueductal grey and the cerebral aqueduct. Same somatotopism of the pons. (Thalamus and cortex) After the midbrain it will continue and it will synapse at the level of the VPL nuclei of the thalamus and the third order neurons will reach the post central gyrus. At the level of the thalamus the somatotopism is maintained as cranio-caudal, medio-lateral. The information coming from head and neck (trigeminus) neurons will be located more medial and will have a proper nucleus of the thalamus and will enter in the VPM, which is the continuation of the VPL. To reach the cortex the neurons will travel into the internal capsule and the corona radiata will spread the neurons to reach the cortex. Here the fibers will turn because the internal capsule has an anteroposterior direction, and the hemispheres are organized in a caudal-cranial, media-lateral manner which is the initial somatotopism. So, the homunculus will present from lateral to medial the head to the lower limbs. 4 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways Summary somatotopism 1) Spinal cord (posterior column): cranio-caudal, latero- medial 2) Brainstem (medial lemniscus): cranio-caudal, medio- lateral 3) Thalamus (VPL nucleus): cranio-caudal, medio-lateral 4) Cerebral cortex (post central gyrus): cranio-caudal, latero-medial Collaterals Max 15% but usually less of the fibers of the fasciculus gracilis and cuneatus synapse in lamina III-I. In the image you can see the course 5 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways 4. Lateral division: Lateral division is larger because in this system there are many boundless. Focusing on the conscious pathways here are conveyed the signals of light touch, pressure, thermal and pain. The largest tracts in this division are the spinothalamic, because the main target of this pathway will be the thalamus and is split in 2 subtract: the anterior spinothalamic tract which travels in the anterior funiculus, and the lateral spinothalamic tract. In the lateral division there is also the spino-reticular tract, which is highly modulated because it is formed by fibers that stop many times at different levels of the reticular formation (complex of nuclei creating long columns at the level of the brainstem). The reticular formation is important in both ascending and descending pathway. In the lateral division there are tracts that arrive at specific nuclei of the brainstem as well such as the spino-olivary tract which synapse at the olivary complex or the spino-mesencephalic tract whose fibers synapse at the periaqueductal grey. Some other tracts instead arrive at the level of the lamina quadrigemina. Anterior spinothalamic tract The anterior spinothalamic tract occupies a quite large area of the anterior funiculus therefore it is considered the main one, but there are other tracts that travel with it (e.g. the spino-olivary tract involved in proprioception). The receptors of the first order neurons are the one of light touch and pressure and their somas are located into the posterior root ganglia; They enter the spinal cord at the level of the posterior horn of the grey matter where they synapse. It Is possible to have an interneuron at the level of the substantia gelatinosa and then once in the nucleus proprius the ascending pathway can begin. The neurons entering in the spinal cord can give off some collaterals which continue into the intersegmental tracts, the dorsolateral tract of Lissauer. On the contrary, the vast majority of neurons immediately after they synapse at the level of the neuromere of entrance they will decussate passing across the grey commissure and white commissure to arrive at the anterior funiculus of the opposite side. From here they will ascend to arrive at the main target which is the thalamus: the nucleus targeted is the VPL nucleus, the same one targeted by the medial division. From the VPL neurons will continue in the post central gyrus of the cortex passing through the internal capsule. 6 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways Lateral spinothalamic tract: lateral division The lateral spinothalamic tract lateral divion follows mainly the same pathway as the anterior, but here information of pain and temperature are conveyed.. The most lateral fibers of the lateral spinothalamic tract vehicle the perception of acute, very discriminative pain perception and it is conventionally defined as Neo because was acquired phylogenically relatively recently. Lateral spinothalamic tract: medial division 7 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways The neurons in the medial division stop on the way to integrate the new signal to enrich it with emotional aspects and with previous experiences lived by the subject. In order to do this, in the spinal cord the neurons will follow the same pathway of the lateral division, but at the level of the brainstem they can stop at different level such as the reticular formation in the medulla where interneurons can integrate the signal from here they will ascend in the reticulothalamic tract; they can stop at the periacqueductal gray, or at the level of the diencephalon they can stop at the hypothalamus where information from the vegetative system will arrive and integrate with the somatic information. Finally, they all will arrive to the thalamus but this time they synapse at the intralaminar and centromedial nuclei, which are non-specific nuclei of the thalamus. From here they will continue in the insular cortex, the frontal opercle (which is the portions of lobes covering the insular gyrus) but they can also go into the limbic system, or in the orbito-frontal cortex. At the end they can also reach the primary somatosensory cortex, but it is not necessary. The receptor of this pathway will be the nociceptors and the first order neuron will be either an A fiber or a C fiber. Somatotopic organization of the spinal lemniscus Through the lateral division we have 1. Spinal cord (spinothalamic tract): cranio-caudal medio-lateral 2. Brainstem (spinal lemniscus): cranio-caudal medio-lateral 3. Thalamus (VLP nucleus): cranio-caudal medio-lateral 4. Cerebral cortex: cranio-caudal medio-lateral, the same of the medial division To complete the spinal lemniscus description, the somatotopism has to be considered. Besides having the anterior and lateral funiculi, but the origin of the information has to be considered as well. The information from the lateral position is exactly the opposite of the medial division, ie, the information from the leg is located more laterally, and the portion from the upper limb is located more medially. The reason it is opposite is quite simple, it’s because the information is entering from below, medially, and then is collected as before. Axial section passing through the superior portion of the cervical spinal Moving to the opposite side requires crossing the grey cord matter. 8 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways In the spinal lemniscus we have an opposite somatotopism into the spinal cord in respect to the fasciculus gracilis (dorsal column). Then it is ascended to the thalamus, after which the VPL, and from there it is turned into the internal capsule. The spinal cord has a difference of somatotopism of the medial and lateral group. Spino-reticular tract The reticular formation is a very big relay nucleus made by 3 columns of neurons: median, medial and lateral column. Nuclei receive from both ascending fibres and from supraxial organ, in order to participate in the creation of descending pathways. Therefore, it contains interneurons of sensory and motor system It receives collaterals of the spinothalamic tract and it mainly activates the nuclei of thalamus in a diffuse way, these nuclei are specific and activate the entire cortex, maintaining arousal and consciousness, Entering the medulla oblongata, there are pyramids anteriorly, and dorsally to it there is the medial lemniscus The inferior olivary nucleus is lateral to the pyramids and in respect to the olivary complex there is the spinal lemniscus posteriorly. Axial section passing through the medulla oblongata at the level of the inferior olivary nucleus Ascending pain pathways 9 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways The 3 major ascending nociceptive pathways are 1. Spinothalamic (at the level of the medulla and reaches the thalamus) Neo-spinothalamic (acute pain): A delta fibers, Laminae I and V, SAL, reticular formation, VPL and intralaminar thalamic nuclei Paleo-spinothalamic (chronic pain): C fibers, substantia gelatinosa (laminae II and III), lamina V, SAL, reticular formation, intralaminar thalamic nuclei 2. Spinoreticular (at the level of the medulla and reaches the thalamus, like spinothalamic) Collateral branches of the spinothalamic tract to the reticular formation and then to the thalamic nuclei: diffuse and continuous activation of the cerebral cortex A representation of what can be found in the brainstem as a possible synapse for the fibres called spinoreticula. These are fiber collaterals of a main bundle which is spinotalamic, so some of these have many stops into the reticular formation, so a spinal reticula is created. Into the reticular formation, then to the thalamus with the objective to activate all the thalamus’ nuclei because the reticular formation is involved in arousal maintenance. 3. Spinomesencephalic It is at the level of the pons, it reaches the periacqueductal gray, stops there and gives rise to the descending pathways that can modulate pain 10 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways So there is spinothalamic as a major group, spinoreticula as a main stop at the level of the reticula formation there can also be some synapses in the reticula formation of the pons. There is also a third possibility, spinomesencephalic, a very important station for pain, since it is tighly related to the descending system Unconscious general somatosensory pathways Fibers of unconscious pathway also travel into the anterolateral system, but also form spinocerebellar tract, both are located in the lateral funiculus of white matter. They carry muscle joint sense from trunk and lower limbs and, when they reach the medulla oblongata, these fibers willreceive also accessory cuneate fibers, giving rise to the Cuneo cerebellar tract, which adds to the previous spinocerebellar tract, carrying proprioception to cerebellum. Also, from face we have fibers of trigeminocerebellar fibers. 11 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways In the cerebellum there are tracts that travel to the lateral funicule of the white matter into the spinal cord. There are fibers that originate from the spinal posterior root ganglion and receptors of muscles and joints sense for trunk and lower limbs, but when then end of the spinal cord is reached, a nucleus located laterally to the cuneat nucleus can be found. At this location, the origin of another tract can be found that goes to the cerebellum. There are 2 spino-cerebellar tracts that originate from the cerebellum, which enter with afferent fibers to the dorsal horn then move a bit anteriorly with respect to the ones that were seen for the conscious pathway. These 2 cell groups are at the origin of the ascending pathway. The fibers enter and go to a group called nucleus dorsalis, but into this anterior nucleus there are subgroups of neurons. One subgroup, located more ventrally, is called Bechterew’s nucleus gives rise to a ventral spino cerebellar tract. The clark’s nucleus is dorsal and has a different pathway, but both are going to the lateral funiculus Spino-cerebellar Tracts Formed from 2 nuclei: ventral (Bechterew’s nucleus) and dorsal (Clarke’s nucleus), both located at peripheral aspect of the lateral funiculus, so they’re in relation with lateral spinothalamic tract. These nuclei are located on the dorsal horn of the same side of the entrance of sensory fibers. The anterior ventral spinocerebellar tract decussates, while the dorsal spinocerebellar tract is ipsilateral, so from the grey matter axons move to lateral funiculus and ascend. 12 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways In the medulla oblongata, there is thebaccessory cuneate nucleus (receives infos from upper portion of our cervical limbs), which forms the cuneocerebellar tract. Together with the posterior spinocerebellar tract, they enter into the cerebellum, using the inferior cerebellar peduncle of the medulla oblongata. Ventral spinocerebellar tract, which ascend contra-laterally, proceeds even after the medulla, it reaches the midbrain and enters the superior cerebellar peduncle and decussate again, entering the cerebellum through the superior cerebellar peduncles. The dorsal tract is entering white matter lateral funiculus, more dorsally, but remains always ipsilateral. When it reaches the medulla oblongata it goes to the cerebellum. Spino-cervico-thalamic tract The lateral cervical nucleus is located in the dorsal horn of the first neurons of the cervical tract. It is very important since it can give rise to new fibres. There is the possibility, when ascending into the spinothalamic tract, to have some fibres that have a modulation at the level of this nucleus, since it will receive fibres that were ascending in the lateral column. They will synapse and, from this nucleus, fibers will be added to the fasciculus cuneate and gracilis. Information carried is pain, thermal and proprioception, so in the medial lemniscus there is also this information. The remaining pathway will be the same as the medial. NB: In the brainstem the trigeminal lemniscus adds to medial and spinal lemniscus: it carries pressure, pain, temperature, and touch from skin and mucous membranes of the face 13 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways In the medulla oblungata, the info can either enter directly or to stop with the fibers that enter at the cervical portion. The trigeminal system has 3 nerve branches, ophthalmic, maxillary and mandibular, but it also has 3 nuclei and they do not correspond to the branches. They manage different kinds of information, and at their level, there is sensory fibers of all kinds. So there is a quite large group of fibers. When they enter into the brainstem, the nuclei devoted to different fiber types can be located The ophthalmic is the first of those divisions. Trigeminal lemniscus The trigeminal nerve carries infos of pressure, pain, temperature and touch from skin and mucousof the face. These fibers have the first order neuron into the trigeminal ganglion, located in the middle cranial fossa. The ganglion then gives rise to fibers that reach the different nuclei of the trigeminal nerve, located one in the medulla, one in the pons and one in the midbrain. Somatotopism: ophthalmic fibers enter caudally and the mandibular cranially. 14 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways The spinal nucleus of V, located in the medulla, called spinalsince it continues with the substantia gelatinosa of the first neuromers in the cervical portion: infos of temperature and nociception Main nucleus in the pons: infos on discriminative (areas 3, 1, 2) touch andpressure Mesencephalic nucleus: infos on proprioception. This nucleus isvery unique, since here are present first order neurons. So fibers carrying these infos have the first cell into this nucleus. NB Some somatosensory fibers from the face are collected by nerves 7, 9 and 10, not only from trigeminal nerve. For example infos from the external acoustic meatus or the auricle, they enter the nuclei of the trigeminal nerve depending on what type of infosthey bring. From the nuclei of trigeminal nerve we have the origin of 2 ascending tracts: one is dorsal and ipsilateral the other is ventral and crossed —> infos reachbilaterally the VPL of the thalamus. Then we ascend into the primary somatosensory cortex. Pain Reception What is pain? A warning signal about a potential injury that our body can receive, so it isn’t amodification of energy. To sense pain we mostly have free endings located into periphery of our body, that can use differentchemical substances which can conduct slow or fast pain to the CNS. Acute pain —> infos are sharp and pricking, they’re very fast since allow arrival of nociceptiveinformations in 0.1s. Pain is sensed through mechanical or thermal stimulus. It ascends through neo-spinothalamic fibers, starting from A𝜹 fibers (free endings for nociception) Slow pain —> through non myelinated C fibers, slow conducting (1s), burning, aching, and throbbing. It ascends with paleo-spinothalamic fibers. Modulation of pain Afferent fibers, with information of potential injuries, can come from different nociceptors and reach the dorsal horn through A𝜹 or C fibers. They vehiculate info with A𝑎 (Golgi tendon organs)or Aβ (muscle spindles) fibers. So using these fibers from a certain area of our body, the receptors can give us the ideas of which kind of stimulus has happened and if this can be a potential harm for us. All of these fibers enter the dorsal horn, except the ones forming the medial division, which go intothe lateral funiculus and ascend without synapse until medulla oblongata. Example: An A𝑎 fiber can enter in lamina 4 and synapse with a projecting neuron, which gives rise to the spinothalamic tract, ascending with painattribution. This interneuron, in fact, is located into different laminae, so it can also receive an A𝜹 fiber in lamina 5 —> more synapses are 15 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways possible. Into the dorsal horn we have many interneurons, which can receive A𝜹fibers and C fibers and synapse between them. So, there is the possibility to allow tactile information to carry the pain or not —> modulation of the signal, with a possible attenuation or inhibition. In these interneurons of the dorsal horn there is also the arrival of descending fibers, such as cortical or subcortical, which can work on these relay nuclei to modulate the signal fromhigher centers. Gating theory The arrival of 𝑎 and β fibers, into the dorsal horn, can activate projection neurons of the spinothalamic tract (inorder to carry pain infos) and also excite interneurons located between lamina I and II (substantia gelatinosa) able to inhibit the projection neuron. These interneurons can also receive infos from fibers vehiculating pain (es. C fibers) which inhibit these interneurons and, if this happens, the projecting neuroncan allow the signal to continue. These interactions can attenuate and reduce the info, since in these interneurons there is also the arrival ofdescending fibers which can stop the projection thanks to higher centers. Gating theory explains ago-puncture technique: if we activate large diameter fibers through mechanical stimuli, they can prevail on the inhibitory interneurons, since they’re activated and therefore inhibit the pain attribution to the projecting neurons, which will continue with mechanicalstimulus only. Analgetic descending pathways 1. Oppioidopeptidergic (ENK:PAG) – serotoninergic (NRM) – substantiagelatinosa (ENK, dynorphin) 2. Noradrenergic (FRPD) – substantia gelatinosa (ENK, dinorphin) 16 International Medical School - ANATOMY#2 Prof. Della Via -Ascending Pathways Serotonin activity depends on the receptor Fibers from the periacqueductal gray arrive to the NRM and descend on both sides, ending at the dorsal horn, acting on the inhibitory interneurons andclosing the gate. While fibers from the reticular formationcan descend directly or pass at the level of the NRM to reach the substantia gelatinosa andmodulate pain info The analgesia system Endocannabinoid system: endocannabinoids (anandamide, 2- arachinodil-glicerol) produced on demand + CB receptors (CB1 in the nervous system, CB2 in the immune system)-CB1 colocalization with Gabaergic neurons Oppiods (enkephalins, endorphins), serotonin and norepinephrine Presynaptic inhibition of pain transmission Pain Control and Interpretation Descending fiber from the CNS can modulate pain signal giving it an interpretation, which dependson the state of our body in that moment —> emotional control. - Cingulate gyrus: part of the limbic system, it can give to our pain perception the aspect of theemotions that can modify its amplitude. For example, in some subjects with anxiety, this state can amplify the pain, while in others, it can inhibit it - Post-central gyrus: pain related with past experiences - Insular gyrus: visceral pain (autonomic response) 17