Neuroanatomy #12: Cerebellum PDF

Pag. 1 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum NEUROANATOMY #12 - 22.11.21 Cerebellum Prof. Dellavia – 22/11/21 – Author: Filippo Bistagnino – Reviser: Emma Tozzi Spadoni 1. Position...

Pag. 1 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum NEUROANATOMY #12 - 22.11.21 Cerebellum Prof. Dellavia – 22/11/21 – Author: Filippo Bistagnino – Reviser: Emma Tozzi Spadoni 1. Position and structure: The organ is in the posterior cranial fossa and it is dorsal to brainstem, in particular it is necessary to remember the connection between the cerebellum and brainstem. This is done by the cerebellar peduncles which are 3 and are paired. They allow the connection with the midbrain (through superior peduncle), pons (through middle peduncle) and medulla oblongata (through inferior peduncle). The cerebellum has a vermis which is a median structure. The vermis has attached on each side the hemispheres. There are sulci dividing the vermis from the hemisphere. From an inferior view the vermis is more prominent and there is the possibility to see the division of the different lobes by the presence of other sulci which are not longitudinal, like the ones dividing vermis from hemispheres, while they are organized in a medio-lateral direction. Some of the sulci are deep and other less deep, this is due to the fact that the surface of cerebellum has many folds which are called lamellae.  Pag. 2 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum The cerebellum can be divided into 3 lobes. The most ancient one is the one called flocculonodular lobe and it has a portion in the median position called nodule which is an unpaired structure. On both sides there are the flocculus which are paired structures placed in medial to lateral direction. The other lobe (pink) is the anterior lobe, it is the second in order of development. A portion of this lobe is included in the vermis and a portion is included in the hemisphere. The lobules recognizable in the scheme are more visible from anteriorly. It is possible in the image in grey to consider the cerebellum as a book which has been opened. There is a horizontal fissure around the cerebellum dividing it into a superior and inferior surface. This fissure passes mainly at the centre of the posterior lobe. The posterior lobe also called middle lobe (brown) is partly visible in the superior surface and partly in the inferior one. (We do not focus on the lobules, but very well on lobes). The division into lobules is made by less deep sulci recognizable on the surface. The cerebellum is organized differently from the brain. Indeed, the cortex (grey matter) is not divided in areas with different circuits and structures, but it is a sort of a replicating model. There are similar circuits independently from the region that it is considered. There is different information which are processed, so it is important to analyse the somatotopism inside. However, the organization is similar, and it is possible to recognize the correspondence of one specific signal inside one lobule. The most representative lobe is the posterior one which is crossed by the horizontal fissure. There is also a primary fissure dividing the posterior lobe from the anterior one. The Flocculonodular lobe is not attached, but there is a gap in between the rest of the cerebellum and this lobe. This gap is represented by the posterolateral fissure. The phylogenesis is carrying new info and from a functional point of view there are different areas in different lobes.  Pag. 3 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum If the cerebellum is cut, it is possible to see the inner structure which presents the white matter hosting inside the nuclei of grey matter which are part in the vermis and part in the hemispheres. The white matter moves creating branches inside the peripherical part of the organ, which is the cortex, creating the typical arbore vitae structure. The nuclei can be divided into 3 groups (4 nuclei per side). There is the fastigial nucleus inside the vermis. Then there are 2 nuclei more lateral: one is located between the vermis and the hemisphere and is called globose nucleus; the second nucleus is more lateral and it is called the emboliform nucleus located in the medial aspect of the 2 hemispheres. The last nucleus is the dentate nucleus which is in the lateral portion of the hemispheres. It is the largest nucleus as well as the most recently developed one. Functionally it is possible to couple the globose and emboliform nuclei forming the composite nucleus (as they have similar fibres exiting). The nuclei form the output of the cerebellum and give rise to efferent fibres. The nuclei can also receive collaterals from the fibres that are entering. The fibres entering the cerebellum, once inside give collateral to nuclei and continue to reach the cortex.  Pag. 4 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum 2. Layers of the cortex and cells type The cortex has 3 layers in any part of the cerebellum. The inner layer one is called granular layer and contains granular cells. These cells synapse with the fibres entering the cerebellum. These cells are many in the deep portion of the cerebellum, while in between the granule cells there can even be Golgi cells. They are not completely inside this layer, but with the prolongment of the soma of the cell can even enter other layers. Golgi cells are important for inhibitory circuits. In the intermediate level there is the Purkinje cells which have a soma in this layer, and it has the shape of a pear. The “pear-shaped soma” then continues with huge arborization of the dendrite which climb up to reach the most external surface of the cortex. The dendrites completely occupy the external layer where part of these dendrites find also other small cells. These are the stellate cells which are spread and are located deeper in the external layer compared to another type of cells, the basket cells, which are more superficial. The Purkinje cells have an axon which is going from the cortex to the nuclei. Inside one lamella, at the center there is a pillar of white matter which hosts the afferent fibres which arrive from the peduncles and reach the cortex of the cerebellum. The first possible stop for these afferent fibres is at the level of the granule cells. In this white matter there are also efferent fibres which are the axons of the Purkinje cells going from the cortex to the nuclei located deep in the white matter. The nuclei will then give rise to efferent fibres form the cerebellum which exit again through the peduncle. The afferent fibres can sub-divided in 2 types: one which is the most representative which are the mossy fibres (group of fibres carrying proprioceptive info, visual info, vestibular info and so on). These fibres enter the cerebellum and reach the granules. The other group of the afferent fibres do not create synapse with granules but enter the cortex and climb along the dendrites of the Purkinje cells until the surface of the cortex, these are called climbing fibres. The climbing fibres are all coming from a complex of nuclei, inferior olivary complex (located inside the medulla). If it is necessary for the information to be processed immediately, the entrance point (the granular layer) will be skipped and the fibres will continue until they will synapse with the Purkinje cells at the level of their dendrites.  Pag. 5 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum Referring to the image: the granules are the cells with a small and circular shape and dendrites all around. From the body cells, the axon of the granule cells can be seen, and it moves perpendicularly from inner layer to outer layer. Before reaching the surface, the axon is divided into 2 parts (T shape division) at the level of the external surface. One part of the axon will move following one side of the lamella and the other division will follow the opposite way; these fibres are called parallel fibres. These fibres can synapse on the dendrites of the Purkinje cells as they pass through the arborization of the dendrite of the Purkinje cells. When there is the synapse, the Purkinje will take the signal and move the signal towards the nuclei. In this image it is possible to see the localization of the other cells. Golgi cells are not completely occupying the inner layer but are part in the inner and part in the other layers. They can synapse on one side on the granule cells, mossy fibres or climbing ending and then on the other side they can synapse with both parallel fibres and Purkinje cells. The Golgi cells, basket cells and stellate cells are used to create additional circuits to the basic one, which involves only the granular and Purkinje.  Pag. 6 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum The afferent fibres reach the inner layer and form the glomerulus (formed by granules and afferent fibres). The mossy fibres, that synapse with granules, is completely encapsulated and inside the glial capsule there is the passage of other terminals, which can be Golgi cells. At this level there is both the axon and the dendritic spine of the Golgi cell. If the signal follows a basic signal, the afferent fibre reaches the glomerulus and then the granules cell will take the signal. Entering the cerebellum, the mossy fibres are used for example. There is a collateral reaching the nuclei or the fibre can continue to the cortex. The mossy fibres activate the nuclei of the cerebellum or pass the signal to the granule cell. In general, first of all the nuclei are activated so that they are ready to give the output and then the signal will be processed in the cortex to decide if there is the possibility to switch off the nuclei. The mossy fibres reach the glomerulus and have synapse in the granule cells which with their axon enter the external layer and form the parallel fibres. These fibres will synapse on dendrites of the Purkinje cells, which create corridors of fibres placed perpendicular to the parallel fibres. Parallel fibres excite Purkinje cells and send info to nuclei. The Purkinje cells are inhibitory. The nuclei are first activated and then, with the Purkinje cells, it is decided whether to switch off the deep nuclei or not. The cerebellum work with inhibition. On Purkinje cells there are other cells acting to inhibit the Purkinje cells (double inhibitionàdeep nuclei remain active) and this allows to decide which part of the signal can exit according to which nucleus remains active or not.  Pag. 7 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum The stellate cells have the body cell in the external layer and their dendrites are all round. They synapse with the parallel fibres and through their axon can inhibit the Purkinje cells. However, the inhibition does not take place within the same corridor (along the long axis of the lamina), but on a transvers aspect (perpendicular to the long axis of the lamina). They act laterallyà lateral inhibition. Basket cells work in a similar wayà lateral inhibition. The difference is that in the stellate the inhibition of stellate on Purkinje takes place on the dendrites, whereas the basket cells take again information from the parallel fibres, but they have the axon acting on the body cell of the Purkinje. In the external layer there are the parallel fibres or axons of the stellate cells, whereas in the intermediate layer there can be axons of the basket cells. Golgi cells work on an inner aspect. They can occupy the whole thickness of the cortex, but they act at the level of the glomeruli. The Golgi cells receive part of the signal as collaterals of the afferent fibres (such as collaterals form mossy fibres). The climbing fibres work again with collaterals to the nuclei (this means that all the fibres entering the cerebellum can activate the deep nuclei), but then they continue the course. The climbing fibres mainly enter the intermediate layer to reach the arborization of the Purkinje cells in the external layer. These climbing fibres can also activate Golgi cells. Golgi cells can hence be activated by the entrance signal of both mossy, climbing fibres and even parallel fibres. In turn, Golgi cells will inhibit the glomerulus. Summarizing: The mossy fibres enter and synapse on the granular cellsàgranular cells will create the parallel fibresà Purkinje cells are activatedà Purkinje cells will inhibit the deep nuclei. These nuclei were previously activated by both mossy and climbing fibres. The other circuit is the one involving the climbing fibres from the inferior olivary nucleus, which enter to excite the Purkinje or activate Golgi cells. Possible inhibitory circuits involve the presence of Golgi cells or as alternative Basket cells or stellate cells which all inhibit the Purkinje cells but at different level. The basket and stellate cells take the signal from parallel fibres. These circuits are always the same, what changes is the type of info processed (proprioceptive, vestibular, and so on).  Pag. 8 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum 3. Functional areas and somatotopism: The focus of this part will be on the typology of the signal and on what specific areas are devoted to certain types of signals. Considering the morphology, as previously seen, there are three distinguished areas: flocculonodular, anterior and posterior. They can be associated to distinguished functional areas. The flucculonodular is the most ancient and is also called archi-cerebellum. From an evolutionary point of view, that is the area that processed information first, subsequently more parts were developed, for instance the anterior lobe. Therefore, technically it shouldn’t be considered a functional area in itself. Following the same principle of evolution, the anterior lobe can be called paleo-cerebellum and the posterior can be called neo-cerebellum. The somatotopism is particularly important for the proprioception (spino-cerebellum in particular) and it is postero-anterior cranio-caudal: the image represents the cerebellum having been opened “like a book”. The horizontal fissure, at the centre of the vermis, crosses an area dedicated to visual and auditory processing (also specific special senses arrive at the cerebellum). - Spino-cerebellum; big portion of anterior lobe (vermal-intermediate zone; it is in fact at the level of vermis and paravermis) and it represents the connection with information regarding proprioception, most of its fibers derive from the spinocerebellar tracts, but they can also arrive from the head and neck, so proprioception of cranial portion - Ponto-cerebellum: lateral zone; this is the most recent part to develop, and it is connected to the cortex, this area is responsible for the correlation system that was mentioned at the beginning. Information is incoming from the cerebral cortex and passing through the pons; cortico-ponto- cerebellar tracts enter at the level of the lateral hemispheres. Information gets processed in the lateral zone and exits through the dedicated nucleus (dentate) that brings information back to the cortex passing through cerebellar peduncle and the thalamus. - Vestibulo-cerebellum since it’s connected to the vestibular nuclei. It receives afferent fibres from the nuclei of the vestibular system and receive fibres directly from Scarpa ganglion which has collateral that escape the entrance into the brainstem to enter directly the cerebellum (flucculonodular lobe; devoted to the processing of information related to posture) In the case of visual and auditory information, these come from the tectum, so, lamina quadrigemina. Important because management of sensory information is needed for the coordination of movement.  Pag. 9 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum 4. Major inputs to the cerebellum: - Pontine nuclei (basilar nuclei of the pons) - Inferior olivary nuclei - Vestibular nuclei - Spinal cord It’s important to know what are the inputs and outputs/spino-cerebellar tracts to associate them in the correct part of the peduncles. The nuclei give rise to the outputs. Following image shows the main cerebellar connections:  Pag. 10 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum 5. Cerebellar peduncles: - Superior peduncle à midbrain - Middle peduncle à pons - Inferior peduncle à medulla oblongata Each peduncle may be used to enter or exit the cerebellum. Inferior peduncle: mainly contains afferent fibres. For example, fibres going to the spino-cerebellum, between vermis and paravermis, which are of the spino-cerebellar tract, bring proprioceptive information, pass through the inferior cerebellar peduncle (also called posterior or dorsal spinocerebellar tract). - Afferent fibres: Posterior spinocerebellar tract: it’s direct since it remains ipsilateral in the white matter of the spinal cord, ascends in the lateral funiculus of spinal cord, reaches medulla oblongata and peduncle to reach vermis and paravermis as said before. In this area there is also the arrival of fibres from the neck. The cuneo-cerebellar tract originates from the accessory cuneate nucleus which is lateral to the proper cuneate nucleus (one of the two nuclei of the origin of the medial lemniscus). In the accessory cuneate nucleus, there is the arrival of fibres for the proprioception of the neck and girdle which enter the cerebellum through the inferior peduncle. There is even the arrival of proprioception from the head (masticatory muscles and tempo mandibular joint)  Pag. 11 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum which enter through the inferior cerebella peduncle and belong to the trigemino-cerebellar tract. Apart from proprioception there are afferents which use the inferior cerebellar peduncle to reach then the flocculonodular lobe to be processed. Some fibres passing in the inferior peduncle can even reach the vermis to be integrated here creating circuits together with other inputs processed in the vermis: like visual and auditory (as can be seen in the image). The vestibular is mainly organized targeting the flocculonodular lobe arriving through the vestibulo-cerbellar tract. It is possible to receive even information from the reticular formationà reticulo-cerebellar tract. All these fibres mentioned previously enter through the mossy fibres; in the medulla oblungata there is also the inferior olivary complex which gives rise to climbing fibres entering as well through the inferior peduncle. The fibres from the inferior olive give rise to olivo-cerebellar tract. - Efferent fibres: 1. Cerbello-vestibular tract 2. Cerebello-reticular tract Starting from the nuclei of the vestibulo-cerebellum they reach other nuclei: nucleus for vestibulo- cerebellum is the fastigial nucleus from here fibres reach the vestibular nuclei though the cerebello- vestibular tract or they can go to the reticular formation again though the cerebello-reticular tract. The fastigial is the main one for the exit to the reticular formation, but there is also the composite nucleus, the one of the spino-cerebellum which targets the reticular formation. Fibres here are ipsilateral, meaning that they enter and exit from the same side. Superior cerebellar peduncle: The superior can bring in and out fibres: the majority are exiting though. This is because many fibres enter with a signal to be processed, some of this is information will remain in the cerebellum, for example the ones of the anterior spinocerebellar tract (ascends spinal cord in the lateral funiculus, more anteriorly, crosses in its first decussation at the beginning and ascends contralaterally in the lateral funiculus, reaches the brain stem and continues all the way to the midbrain where it uses the superior cerebellar peduncle to cross in its second decussation. The tecto-cerebellar tract is bringing in visual and auditory stimuli from the colliculi of the lamina quadrigemina. The efferent fibres are more abundant because they may descend back to the spinal cord, or they can bring feedback to the cortex: the cerebello-rubral tract reaches the red nucleus of the midbrain and the rubrospinal tract originates from this nucleus (cerebellum controls the extrapyramidal system because it acts on the red nucleus and creates the lateral descending system from the interposed/composite nucleus). Exiting fibres using the fastigial nucleus mainly bring information back to the vestibular system, for the formation of the descending system involved in the medial division of the descending pathways. This means that it will enter the system that has to do with maintenance of posture, continuing as a vestibulo-spinal tract or it can be used to go the tecto-spinal. Different nuclei of the cerebellum are used to control the different types of descending systems. On the other hand, the other bundle is dedicated to giving feedback to the cortex into  Pag. 12 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum the posterior lobe, where integration of signals occurs. This exits through the dentate nucleus; this is considered to be part of the motor and premotor since it does the checking of time and sequence of motor actions. This information from the cortex has to be integrated with the one from the spinocerebellar tract. Using the superior cerebellar peduncle fibres reach the thalamus doing a decussation (one hemisphere receives contralateral information and gives feedback in contralateral direction) then internal capsule, corona radiata and cortex of telencephalon of opposite side. The exit of the correlation system, dento-thalamic- cortical component, is through the superior peduncle. - Afferent fibres: 1. Anterior spino-cerebellar tract 2. Tecto-cerebellar tract - Efferent fibres: 1. Cerebello-rubral tract 2. Dento-thalamic tract (dento-thalamic-cortical part) Middle cerebellar peduncle: Cortico-ponto-cerebellar pathway (entrance of the correlation sytem): frontal, occipital, parietal and temporal lobes, pontine nuclei, dentate nucleus. This peduncle is also crossing. This tract can be originating from different parts of the telencephalic regions. All these lobes can give rise to fibres that will enter the corona radiata, internal capsule and will then descend in midbrain, synapse in the pons and use the middle peduncle to cross and enter. The precision and coordination of movements is due to the integration of information being processed (the signal has been checked by the basal nuclei to have an integration in respect to what arrives from the thalamus continuously) and the direct connection of cerebellum to muscles. Cerebellum works as a comparator, between info from periphery and cortex. That is why in case of lesions there are alterations at the level of maintenance of posture, function, unsteady gait (oscillations), disturbances of reflexes, hypotonia (reduced muscular resistance to passive movements, ataxia (irregular and weak voluntary movements), nystagmus (rhythmical oscillation of the eyes), asthenia, neutral position of joints, dysmetric and asynergistic movements, dysdiadochokinesia (inability to alternate movements).  Pag. 13 a 13 International Medical School – NEUROANATOMY #12 – prof. DELLAVIA– Cerebellum