PHYS 19 - Spinal Cord to Cortex PDF

PHYS 19 – Spinal Cord to Cortex 1.​ Dorsal roots The posterior aspect of the spinal cord receives sensory fibers, having their cell body in the dorsal root ganglia. Every dorsal root is divided into 6-8 rootlets each of them having a medial and lateral section. a.​ Lateral section T...

PHYS 19 – Spinal Cord to Cortex 1.​ Dorsal roots The posterior aspect of the spinal cord receives sensory fibers, having their cell body in the dorsal root ganglia. Every dorsal root is divided into 6-8 rootlets each of them having a medial and lateral section. a.​ Lateral section The lateral subdivision presents fibers conveying nociception and thermal inputs, therefore Aδ and C fibers. These fibers enter at the level of the Lissauer dorsolateral tract and divide into two branches, one ascending and one descending, to terminate in the dorsal horn where they synapse with the 2nd order neurons either at the same level of entrance or 3/4 segments more cranial. The ascending system created by nociceptors and thermal fibers is fed by 2nd order neurons that have their body located either -​ in lamina I, for specific nociceptors -​ lamina V, where there are a-specific projecting neurons receiving from nociceptors and Aβ fibers (crude touch). The green neuron in the picture below represents an element of the substantia gelatinosa. It is an interneuron which is believed to be involved in the gate theory for the control of pain perception b.​ Medial section The medial section is devoted to feed the DCML dorsal column-medial lemnicus system, by conveying fine touch and vibration sensations. In these section Aβ fibers (fast, myelinated axons coming from the cutaneous receptors) enter in the spinal cord and divide in ascending and descending branches forming the dorsal funiculus (also called dorsal column). The descending branch divides into two fasciculi: -​ the septomarginalis fasciculus -​ the interfascicular fasciculus. The neurons that are present in these fasciculi are the proprioceptive and tactile branches that are going to synapse with the more anterior laminae and mediating the reflexes. The ascending branch instead enter in the dorsal funiculus and terminate at the gracilis and cuneate nuclei. 2.​ Internal structure The white matter is divided in 3 funiculi, also called columns: ​ Ventral funiculus – anterior column ​ Dorsal funiculus – posterior column  ​ Lateral funiculus – lateral column The grey matter is divided in: ​ Ventral horn ​ Dorsal horn ​ Lateral horn – only in the thoracic segment and in the first lumbar where preganglionic bodies of orthosympathetic fibers are located ​ Grey commissure The general organization of the spinal cord is always the same but depending on the location there can be differences in the shape of the structures, mainly of the grey matter. The most striking one is the cervical enlargement in C8 where the anterior horn, mainly lamina XI is very big. This is due to the increased number of motor neuron innervating the structure at the level of C8 and it’s visible also by observing the homunculus where face and hands are very large. The same thing happens in the lumbar and sacral enlargement. In the thoracic segments instead, there is a lateral pronunciation of the grey matter representing the lateral horn which is not visible in the other segments. 3.​ Functional subdivision The spinal cord can be subdivided functionally in several ways: -​ Longitudinally: cells are organized in laminae/columns, which means that also non myelinated fibers can be present in the columns; and axons are organized in white matter columns. -​ Transversally: neurons are organized in an anteroposterior manner (efferent components lies anteriorly, the afferent one more posteriorly) or in a latero-lateral manner (presence of commissural decussations allowing communication between the two sides) -​ Somatotopically: each area corresponds to a part of the body  4.​ Functional organization of the gray matter laminae/columns the grey matter is made of X laminae: from lamina I to IX are in a posteroanterior direction, and the lamina X sits in the midline. -​ Lamina I: lamina marginalis or Waldeyer -​ Lamina II: substantia gelatinosa or Rolando -​ Lamina III, IV, V, VI: nucleus proprius (not able to discern between those laminae) -​ Lamina VII: intermediolateral cell column; clarke’s clumn (nucleus dorsalis); intermediomedial cell column -​ Lamina VIII: internueorns -​ Lamina IX: motorneurons -​ Lamina X: commissural grey a.​ Lamina I – Lamina Marginalis or Waldeyer The dorsomarginal nucleus (Rexed lamina I) extends the entire length of the spinal cord, capping the dorsal horn, and receives afferent fibers carrying pain, temperature, and light touch sensations. It also contributes fibers for the lateral and ventral spinothalamic tracts. It contacts the dorsolateral tract of Lissauer of the white matter. ​ Afferents: dorsal roots and collaterals ​ Efferents: spinothalamic tract with spinal projecting nociceptive neurons. It’s a very specific tract receiving specific nociception neurons and sending second order neuron to the VPL nucleus of the thalamus which in turn will project to the primary somatosensory cortex. b.​ Lamina II – Substantia Gelatinosa The substantia gelatinosa of Rolando (Rexed lamina II) also extends the entire length of the spinal cord. It is densely packed with Golgi type II neurons, known as gelatinosa cells that possess highly branched, unmyelinated axons. These cells receive sensory input from : -​ the central fibers of unipolar neurons of the dorsal root ganglia, delivering pain, temperature, and light touch information. -​ Descending fibers from higher centers (such as the cerebral cortex) form excitatory and inhibitory synapses with the gelatinosa cells, thus modifying the arriving pain and temperature sensations. In the Substantia Gelatinosa there are inhibitory interneurons, synapsing on the Lamina V. They are deactivated by the nociceptors and activated by the cutaneous receptors. ​ Afferents: dorsal roots and descending fibres from the reticular formation (locus coeruleus and raphe magnus project down and affect the enkephalinergic neurons to modulate the pain) ​ Efferents: neurons projecting to more cranial and caudal segments, connecting with other dorsal horn neurons, mainly in the lamina V (interneurons involved in the modulation of pain). These interneurons are able to interfere with the transmission of nociception. This can happen in 2 ways; -​ thanks to a spinal mechanism due to these interneurons -​ thanks to a dispensing system which is fed by the mesencephalic (periaqueductal) grey matter. The mesencephalic periaqueductal grey matter is sensitive to endorphins and projects down to the reticular formation, where it is possible to find the raphe magnus and locus coeruleus nuclei. These two nuclei are then projecting down to the projecting neurons of the nociception. There is no adaptation in the projection of pain to the cortex. There is on th other hand a sensistization: if the exposure to pain perception is too prolonged in time, side effects will occur. This is because the brain, and consequently the body, doesn’t really feel the pain without any interaction or consequence with/on other structures, for example the vegetative system or muscular contraction. Therefore, pain must be controlled, first of all by the body itself and by MD in the case of a pathology. c.​ Lamina III – Nucleus proprius The nucleus proprius (Rexed laminae III and IV) also extends the entire length of the spinal cord. It is composed of densely clustered large nerve cell bodies, located just ventral to the substantia gelatinosa, and receives the central processes of the majority of the unipolar neurons of the dorsal root ganglia. The nucleus proprius : -​ receives pain, light touch, and temperature sensations -​ provides input to the lateral and ventral spinothalamic tracts. A transitional lamina between I and II that are together in the transmission of specific pain and modulation of pain (nociception, pain is the perception). It is the most dorsal portion of the nucleus proprius: the nucleus proprius is made by IV, V and VI. However, it is considered part of the nucleus proprius as well. -​ Afferents: dorsal roots (big neurons receiving dorsal roots). d.​ Lamina 4 (part of nucleus proprius) ​ Afferents: dorsal roots (it receives mainly from the dorsal funiculus, involved in touch) ​ Efferents: partial origin of spinothalamic tract (for crude touch, belonging to the anterolateral system), and projections to lamina II and III. At a rostral level, this lamina continues as the spinal portion of the trigeminal nucleus: so, it is mediating the communication between the spinal cord and the principal nucleus of the trigeminus (cranial component – refined touch; caudal component – nociceptive projections). If these laminae are projected cranially (from the first segment of the spinal cord up) they will bump into the brainstem; in the brainstem there are the cranial nerves, which are taking over the function of the spinal nerves. However, the geometrical organization is a bit lost in the brainstem and laminae cannot be observed anymore. By contrast, nuclei can be observed. If the nucleus proprius is projected in the brainstem (so caudally), it will encounter the caudal portion of the sensitive nucleus of the trigeminus. The trigeminal nerve takes over the somatosensory innervation of the whole head and neck (there are just a few refined exceptions, in which other nerves are in charge of the innervation of some areas). In the trigeminus, the sensory neurons are not located in the brainstem (there is no dorsal root ganglia of the brainstem!) but rather in the Gasserian ganglion. In the Gasserian ganglion are contained all the somatosensory neurons of the head and neck with the exception of the proprioceptors, which are located in the mesencephalic nucleus of the trigeminus. Brief summary on the somatosensory system In the somatosensory system there is the dorsal root ganglia, where 1° sensory neurons are located. The semilunar ganglion of Gasser is in charge of innervating the head and neck. It is the sensory ganglion of the cranial nerve V where it is possible to find all the receptors (thermal, Merkel, Maissner, Pacini, Ruffini, nociceptors...) of the head, neck and oral cavity, but not the proprioceptors. The proprioceptors, which are basically the joints, are different from the rest of the body as they don’t have the Golgi tendon organs and usually lack the muscle spindles (only a few muscles are innervated by muscle spindles, basically just the masseter muscles). The proprioceptors are not originating in a peripheral ganglion, but in the mesencephalic nucleus of the trigeminus which is located inside the brainstem. This is the only difference in terms of where the somatosensory neurons are located. The 1° sensory neurons have to synapse with the 2nd order neurons, which are located in the principal sensitive nucleus of the trigeminus in the brainstem. This nucleus is organized as a cigar, with a very cranial portion dedicated to refined touch and a caudal portion which is dedicated to pain, thermal and proprioception. Looking at the dorsal horn of the first level of the spinal cord, upstairs it is possible to find the most caudal portion of the sensitive nucleus of the trigeminus. In this region the same architecture can be described: there is a sort of Waldeyer’s zone, then substantia gelatinosa and then the nucleus proprius. The other sectors which are innervated by sensory neurons that are not originating by the Gasser ganglion (they are running in other cranial nerves; however, they are very few), end up projecting into the sensitive nucleus of the trigeminus. The general rule is that wherever the fibre is coming from, when it enters the CNS, in order to find the second order neurons, it goes to the 5th nucleus. Therefore, the trigeminus dominates in reception for sure, but also in monitoring as 95% of the fibres are originating from the Gasser ganglion or the mesencephalic nucleus of the trigeminus. e.​ Lamina V and VI Rexed lamina V (neck of the dorsal horn) is located be tween Rexed laminae IV and VI, bordering the base of the dorsal horn. It is less cellular and houses thicker bundles of nerve fibers than most other of the laminae and its lateral aspect is referred to as the formatio reticularis. Rexed lamina VI (base of the dorsal horn) is responsible for the removal of those regions of the extremeties from harm’s way that are exposed to painful stimuli. This lamina is not present throughout the entire length of the spinal cord. Lamina V and VI are related to nociception and thermal sensitivity. Nociceptive info is somatic and visceral (from the internal organs). ​ Afferents: o​ dorsal roots (raw sensory data) o​ corticospinal tract: the corticospinal tract is a descending system that projects mostly to the nucleus proprius but also to other laminae. It also goes to the posterior laminae even though it is considered a motor tract) ​ Efferent: partial origin of spinothalamic tract, for nociception and thermal sensitivity. The spinothalamic tract has all the ascending systems belonging to the anterolateral system. The second order neurons are the ones located in the first lamina which are decussating at the level of the commissure and then going up; the second order projecting neuron belonging to the spinothalamic receives both nociceptive and tactile (there is a convergence), having in between a bridge structure which is an interneuron. Gate theory of pain modulation In lamina V there is a convergence of data and the interneurons involved in the gate theory for pain modulation. Normally, nociception is conveyed up and reach the cortex. In order to reach the cortex, it has to avoid any possible gate which is inhibiting its projection. Nociception can be conveyed up in two ways, through lamina I or lamina V. In lamina V, there are big 2nd order projecting neurons (depicted in red in the image) belonging to the nucleus proprius, which are giving rise to a big portion of the spinothalamic tract. Therefore, if the first Aβ fibre is switched on, the green neuron will be excited and signal goes up (crude touch) If the A∂/C fibre is switched on, the red neuron will be excited and nociception/thermal signals go up. However, the two fibres are both communicating to the inhibitory interneuron (yellow and green structure in the picture) acting on the projecting neuron. -​ The nociceptive A∂ fibres inhibit the interneurons, therefore favouring their projection. β -​ The A fibres (big myelinating fibres) are doing the opposite, meaning that they are switching on the inhibitory interneurons and thus inhibiting the red nucleus. It is important to remember that refined touch doesn’t rely on the anterolateral system, just crude touch does. When the two fibres are independently on, the system will allow their projection. When the Aβ fibres are on, the volume of the projection is decreased depending on the power of the interneuron. This can be explained by the fact that the Aβ fibres are faster and more powerful. The power of the interneurons is the modulation of the excitability of the red nucleus depending on how many A∂ fibres are stimlated when the Aβ fibres are on. This is why when we feel pain, we touch the interested area: to diminish the pain sensation thanks to the cutaneous fibres. This concept is at the base of the gate theory, gating the information with the second order neuron. This is the principle which is at the base of some therapeutic interventions that are stimulating, for example, the dorsal columns in cases of tonic pain; this system never switches off the light, but can be lowered a bit in volume.  f.​ Lamina VII – intermediate zone of spinal cord Rexed lamina VII (intermediate zone of the spinal cord) houses in its lateral aspect the nucleus dorsalis, also known as Clarke’s column. Rexed lamina VII does not extend the entire length of the spinal cord, instead it extends only from C8 to L3. It is located at the base of the dorsal gray column and houses relatively large cell bodies that receive synapses from proprioceptive fibers, which bring information from Golgi tendon organs and muscle spindles. Some of the axons of these large nerve cell bodies travel in the dorsal spinocerebellar tracts. Neuronal groups of the lateral gray column The intermediolateral nucleus (another region of Rexed lamina VII) is composed of the relatively small multipolar cell bodies of preganglionic sympathetic neurons. They are present only between T1 and L2, 3, and they send their axons into the ventral root of the spinal cord to enter the sympa thetic trunk via the white rami communicantes. A similar nucleus, the sacral parasympathetic nucleus is located at sacral levels 2–4. These preganglionic neurons of the sacral outflow of the parasympathetic nervous system are also considered to belong to Rexed lamina VII. ​ Efferents: long projecting propriospinal axons to other spinal segments. The biggest lamina, located in an intermediate position between the dorsal and ventral horns that forms the lateral horn in thoracic and sacral segments; whereas, in the thoracic and upper lumbar portions, there are the pre-ganglionic sympathetic neurons of the ANS. The lamina VII is composed of mainly interneurons that communicate between dorsal and ventral horns. -​ In the thoracic cord, also contains projection neurons of the dorsal nucleus of Clarke, a spinocerebellar relay and the sympathetic preganglionic visceral motor neurons of the intermediolateral cell column (underlying the lateral horn) -​ In the sacral cord, also contains preganglionic visceral motor neurons Internal subdivision of lamina VII ​ Clarke’s nucleus: A group of relay neurons (also called the dorsal nucleus of Clarke) located in the ventromedial aspect of the intermediate gray matter of the spinal cord (lamina VII) in spinal levels T1 through L2–3. It conveys proprioceptive signals originating in the lower body to the ipsilateral cerebellum and the dorsal column nuclei via the ispislateral spinocerebellar tract. Fibres project to the cerebellum, giving origin to one of the main pathways: spinocerebellar ipsilateral tract – tracts fed by proprioception (no conscious perception), giving raw data about the position of the joints, amount of force released by the muscle and length of the muscle. Furthermore, this tract is informing also about the interneurons. The information is transmitted directly because the mossy fibres of the cerebellum are also branches of the proprioceptive axons. The cerebellum is also informed on the actual architecture of the excitability going on in the spinal cord during the movement; the information received is not only the raw data from the proprioceptors, but also about the computational analysis that is occurring in the spinal cord. ​ intermedio-lateral column (lateral nucleus): Lateral in the intermediate grey matter, forms preganglionic orthosympathetic neurons (T1-L2) intermediolateral cell column: Rod-shaped distribution of sympathetic preganglionic neurons in the lateral, interme- diate gray matter of the spinal cord; in thoracic segments, accounts for a lateral protrusion of gray matter into the white matter known as the lateral horn. ​ intermedio-medial column: Lateral to lamina X. It receives dorsal root inputs regarding vegetative reflexes: it is the main area where the vegetative system is receiving the afferent inputs. The afferent branch is originating from the preganglionic neurons which are located from T1 to L2 in the intermedio-lateral column (in the 7th lamina), computing the reflexes with interneurons which are receiving info from the dorsal roots which are also conveying vegetative information, in order to be transmitted to the preganglionic neurons. Basically, the 7th lamina, together with the dorsal roots, in the intermedio-lateral/medial columns, belong to the vegetative world in the spinal cord. ​ Vegetative sacral nucleus: lateral in lamina VII (S2 –S4, innervating the pelvic organs), forms preganglionic parasympathetic neurons. In the sacral region there are no preganglionic orthosympathetic neurons, therefore some of the other neurons can be missing. However, it’s possible to detect nuclei where the parasympathetic preganglionic neurons are located. g.​ Lamina VIII Hosting interneurons, located medially in the ventral horn: ​ Afferents: neurons receiving from vestibular and reticulospinal descending inputs ​ Efferents: ipsilateral and contralateral projections to lamina 7 and 9 (same or different segments). h.​ Lamina IX The nuclei of the ventral gray column are composed of both large and small multipolar motoneurons whose axons leave the spinal cord via the ventral rootlets. The large motoneurons give rise to alpha efferents that supply skeletal muscles with motor innervation, whereas the smaller motoneurons supply gamma efferents to intrafusal muscle fibers of muscle spindles. An additional group of neurons, interneurons, are also located in the ventral gray column. Due to the location of their soma, these nerve cells are subdivided into three major groups: -​ medial, -​ central, -​ lateral. The medial group (Rexed lamina IX) extends almost the entire length of the spinal cord (with the possible exceptions of L5 and S1). Between T1 and L4 it is subdivided into two components, the dorsomedial and ventromedial groups. The motoneurons of the medial group provide innervation for the skeletal muscles of the abdomen, the intercostal mus cles, and the muscles of the neck. The central group (Rexed lamina IX) is the smallest of the three groups and its distribution is not very extensive. The central group is present only in the cervical and lumbosa cral segments of the spinal cord. Two regions of the cervical aspect of the central group have special names, the phren ic nucleus and the accessory nucleus. The phrenic nucleus (extending from C3 to C6) is responsible for the innervation of the diaphragm and the accessory nucleus (extending from C1 to C6) is responsible for innervation of the sternocleido mastoid and trapezius muscles. Cells of the accessory nucle us provide fibers for the spinal root of cranial nerve XI (the spinal accessory nerve). The lumbosacral aspect of the cen tral group (L2–S2) is known as the lumbosacral group and its function is not known. The lateral group (Rexed lamina IX) is present only in the regions of the spinal cord responsible for the motor innerva tion of the upper and lower extremities (C4–T1 and L2–S3). Hosting motor neurons, axons exit through the ventral roots, it is divided into four columns (ventromedial, ventrolateral, dorsolateral and central) with a somatotopism: proximal muscles are located ventromedially and distal muscles, dorsolaterally, flexors are located dorsally to extensors. Important segments in lamina 9: there are skeletal muscles that are sustaining vital functions, for example ventilation. ​ C2-C5 ventromedial = phrenic nucleus, hosting motor neurons to diaphragm muscles, receives bilateral information from the nucleus of solitary tract; it is fed by a nucleus of the vagus nerve ​ S1-S2 ventrolateral = Onuf nucleus, hosting motor neurons to pelvic muscles (sphincters) ​ C1-C5 lateral = accessory spinal nucleus (11th cranial nerve), receives corticospinal tract bilateral inputs to control proximal muscles of the neck (trapezius and sternocleidomastoid, connecting the neck to the rest of the body)  i.​ Lamina X The gray matter that surrounds the central canal of the spinal cord is known as the gray commissure (periependymal gray) and the substantia gelatinosa centralis (both Rexed lamina X). The gray commissure is subdivided into a posterior gray commissure and an anterior gray commissure by the central canal. The gray commissures and the substantia gelatinosa centralis extend the entire length of the spinal cord and are believed to be associated with the autonomic nervous sys tem. Frequently, Rexed laminae VI, VII, and X are collectively known as the intermediate zone of the spinal cord gray matter. Located around the central canal. Hosts small neurons, microglia and crossing axons basically fed by sensory inputs. -​ Afferents: dorsal roots inputs. 5.​ Systems of fibres running in the spinal cord White matter in the spinal cord is used to communicate between spinal cord segments and not only with higher centres. Columns in the spinal cord white matter: -​ Intraspinal (meaning neurons that are connecting different segments of the spinal cord; these neurons are running in the spinal cord) -​ Descending motor -​ Ascending sensory -​ Sympathetic and parasympathetic  6.​ Intraspinal system: fasciculus proprius Origins on the propriospinal neurons of the nucleus proprius (dorsal horn, lamina 3-5). It is fundamental for the coordination of multiple segments muscles/nuclei. It accounts for 30% of white matter; however, this tract runs near the grey matter 7.​ Descending system ​ Medial – coming from the brainstem, through these tracts: vestibulospinal from vestibular nucleus, reticulospinal from the reticular formation, tectospinal from the superior colliculus and medial longitudinal fasciculus. Connects with the ventromedial grey matter for the control of axial and proximal muscles (terminate in lamina 8-9). Vestibulospinal and reticulospinal are mainly involved in posture (ipsilateral projections), while the tectospinal is involved in head and eye movements (so it reaches only cortical segments, contralateral projections). ​ Lateral – corticospinal and rubrospinal, coming from the cortex and red nucleus respectively. target the dorsolateral grey matter of the ventral laminae for the control of distal muscles (limb muscles). Corticospinal projections are 80% contralateral and 20% ipsilateral, the projections especially target propriospinal, interneurons and motor neurons in the spinal cord. The rubrospinal projects contralaterally on interneurons. ​ Aminergic – from nucleus coeruleus and raphe in the brainstem, forms diffuse projections in the spinal cord, uses serotonin (coeruleus-spinal tract), noradrenaline (raphe-spinal system) and dopamine (ventral tegmentum system) as NT for modulation of spinal excitability and internal activity, providing a background excitation to spinal neurons (puts them in a state closer to the threshold, the neurons is not discharging) but also playing a role in modulation of pain. ​ Vegetative – from upper centres to the spinal cord preganglionic neurons to act in the periphery. The neurons are grouped in cardiovascular and respiratory centres in the brainstem and even in upper centres like the hypothalamus, through the dorsal longitudinal fasciculus targeting the brainstem and spinal cord. Once the periaqueductal grey is activated, it will activate diffusely the neurons which are contained in this structure, that are sensitive to endorphins (internal opioids). These neurons in the periaqueductal grey project to locus coeruleus and the raphe nucleus, which are in turn projecting down to the second order (red) neurons; this is the most powerful analgesic system ever. Morphine and enkephalins are not randomly diffusing inside our body, in fact they are acting in the periaqueductal grey, then going to the brainstem and finally targeting the second order neurons. That’s why morphine is the most powerful opioid, as it is able to increase the volume of this descending system acting on different levels. There are also interneurons that are sensitive to enkephalins in the spinal cord, which can be used for example to release morphine directly in the spinal cord. It’s important to remember that pain modulation is exerted at the level of the spinal cord but also top down. 8.​ Ascending system ​ Posterior column – medial lemniscus: refined touch ​ Anterolateral-spinal lemniscus: pain and crude touch ​ Spinocerebellar tracts: nociception ​ Spino-medullo-thalamic tract ​ Spino-cervico-thalamic tract ​ Spino-olivary tract ​ Spino-tectal tract