CEREBELLUM

June 3, 2024
0
0
Зміст

Cerebellum.Hemispheres of the brain.

NERVous  SYSTEM

Using lectures (on the web-page of the department posted the presentation text and lectures), books, additional literature and other sources, students must to prepare the following theoretical questions:

1.     Cerebellum: general structure and function.

2.     Layers of the gray matter cortex, characteristic of each neuron, which one can find in the cortex.

3.     Afferent and efferent tracks of the cerebellum.

4.     Main structural peculiarities of the cerebellum gray matter.

5.     The structure and role of the reticular formation tube.

6.     Large hemispheres.

7.     Cytoarchitecture and myeloarchitecture of cerebral cortex.

8.     Morphofunctional characteristic of cerebral cortex neurons.

9.     The agranular and granular types of cerebral cortex.

10.         Describe the blood – brain barrier in terms of its structural correlates and its function.

11.                                                                                 Autonomic nervous system general morphofunctional characteristic. Classification.

12.                                                                                 Nervous system sympathetic portion. Disposition of the central nuclei and peripheral (extramural) ganglia.

13.                                                                                 Types of the autonomic ganglia neurons.

14.                                                                                 Structural particularities of the pre- and postganglionic fibers.

15.                                                                                 Parasympathetic portion of the autonomic nervous system. Central nuclei disposition and intramural ganglia particularities.

16.                                                                                 Autonomic reflectory arch specific feature, its morphologic compartments.

 

The location and degree of development of the human brain is the result of millions of years of evolution. Both functionally and structurally the primary centers for control and regulation of all nervous system function have become centralized in a process called encephalization. In lower animals the spinal cord has a great degree in independence from the brain, while in the human spinal cord function is directly under the regulation of the brain. The functional development of the brain distinguishes humans from lower animals, but anatomic differences are not as apparent. If we compare our brain with that of other primates, we can find the same basic structures in both; however, upon closer study, we find there are marked differences in degrees of development. This developmental change is in the form of more extensive neuron tracts in the human brain and a much greater degree of synaptic connections betweeeuron cell bodies.

Nervous system is a special highly organized system (which consists of nervous tissue and connective) – intercommunicating network of neurons that constitute most sensory receptors, the conducting pathways and the sites of integration and analysis. The function of the nervous system is to receive stimuli from both internal and external environments, to analyze and integrate them, to produce appropriate coordinated responses in various effector organs.

Anatomically it is divided into the central nervous system (CNS), comprising the brain and spinal cord, and the peripheral nervous system (PNS), which constitutes all nervous tissue outside the CNS (peripheral nerves, ganglia, plexus and nervous endings).

The nervous system of a human coordinates the activity of the muscles, monitors the organs, constructs and also stops input from the senses, and initiates actions. Prominent participants in a nervous system include neurons and nerves, which play roles in such coordination. All parts of the nervous system are made of nervous tissue.

The brain has three main parts that interact with the nervous system: the cerebrum, the cerebellum, and the medulla oblongata. Examples of the cerebrum’s tasks include high-order thinking and learning, while the cerebellum manages learned automatic bodily functions, including walking, jumping, and running. The medulla processes simple body functions, such as breathing and digestion

The spinal cord is the area where reflexes are made. Split-second decisions do not go back to the brain and then back to the organ or body part. This would take too long and the nerve impulse would arrive too late to prevent the stimulus from becoming reality. For instance, if a ball was thrown at an individual’s head, the reflex to move out of the way would come from the spine, not the brain, increasing reaction time. The spine is also the “highway” which passes orders from the brain to motor nerves.

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image002.jpg

The general functional organization of the central and peripheral nervous systems.

 

Functionally the nervous system is divided into the somatic portion that is involved in voluntary functions and autonomic one, which exerts control over many involuntary functions.

Histologically, however, the entire nervous system merely consists of variations in the arrangement of neurons and their supporting structures.

 

NERVOUS SYSTEM ORIGIN

Neurulation is a part of organogenesis in vertebrateembryos. This mean the formation of nerve tube and begins at the stage of late gastrulation (14-17 days of embryogenesis). Steps of neurulation include the formation of the dorsal nerve cord, and the eventual formation of the central nervous system. The process begins when the notochordinduces the formation of the central nervous system (CNS) by signaling the ectoderm germ layerabove it to form the thick and flat neural plate. The neural plate folds in upon itself to form the neural tube, which will later differentiate into the spinal cordand the brain, eventually forming the central nervous system.

Different portions of the neural tube form by two different processes, called primary and secondary neurulation, in different species.

In primary neurulation, the neural plate creases inward until the edges come in contact and fuse.

In secondary neurulation, the tube forms by hollowing out of the interior of a solid precursor.

Transverse sections that show the progression of the neural plate to the neural groove from bottom to top

 

Transverse sections that show the progression of the neural plate to the neural groove from bottom to top.

 

Primary neurulation.  Induction

 

Primary neurulation occurs in response to soluble growth factors secreted by the notochord. Ectodermal cells are induced to form neuroectoderm from a variety of signals. Ectoderm sends and receives signals of BMP4 (bone morphogenic protein) and cells which receive BMP4 signal develop into epidermis. The inhibitory signals chordin, noggin and follistatin are needed to form neural plate. These inhibitory signals are created and emitted by the notochord. Cells which do not receive BMP4 signaling due to the effects of the inhibitory signals will develop into the anterior neuroectoderm cells of the neural plate. Cells which receive FGF (fibroblast growth factor) in addition to the inhibitory signals form posterior neural plate cells.

Shape Change

The cells of the neural plate are signaled to become high-columnar and can be identified through microscopy as different from the surrounding epiblastic ectoderm. The cells move laterally and away from the central axis and change into a truncated pyramid shape. This pyramid shape is achieved through tubulin and actin in the apical portion of the cell which constricts as they move. The variation in cell shapes is partially determined by the location of the nucleus within the cell, causing bulging in areas of the cells forcing the height and shape of the cell to change.

Folding

The process of the flat neural plate folding into the cylindrical neural tube is termed primary neurulation. As a result of the cellular shape changes, the neural plate forms the medial hinge point (MHP). The expanding epidermis puts pressure on the MHP and causes the neural plate to fold resulting in neural folds and the creation of the neural groove. The neural folds form dorsolateral hinge points (DLHP) and pressure on this hinge causes the neural folds to meet and fuse at the midline. The fusion requires the regulation of cell adhesion molecules. The neural plate switches from E-cadherin expression to N-cadherin and N-CAM expression to recognize each other as the same tissue and close the tube. This change in expression stops the binding of the neural tube to the epidermis.

The notochord plays an integral role in the development of the neural tube. Prior to neurulation, during the migration of epiblastic endoderm cells towards the hypoblastic endoderm, the notochordal process opens into an arch termed the notochordal plate and attaches overlying neuroepithelium of the neural plate. The notochordal plate then serves as an anchor for the neural plate and pushes the two edges of the plate upwards while keeping the middle section anchored. Some of the notochodral cells become incorporated into the center sectioeural plate to later form the floor plate of the neural tube. The notochord plate separates and forms the solid notochord.

The folding of the neural tube to form an actual tube does not occur all at once. Instead, it begins approximately at the level of the fourth somite at Carnegie stage 9 (around embryonic day 20 in humans). The lateral edges of the neural plate touch in the midline and join together. This continues both cranially (toward the head) and caudally (toward the tail). The openings that are formed at the cranial and caudal regions are termed the cranial and caudal neuropores. In human embryos, the cranial neuropore closes approximately on day 25 and the caudal neuropore on day 27 (Carnegie stages 11 and 13 respectively).

Patterning

 

Transverse section of the neural tube showing the floor plate and roof plate

 

Transverse section of the neural tube showing the floor plate and roof plate

After SHh from the notocord induces its formation, the floor plate of the incipient neural tube also secretes SHH. After closure, the neural tube forms a basal plate or floor plate and an alar plate or roof plate in response to the combined effects of Shh and factors including BMP4 secreted by the roof plate. The basal plate forms most of the ventral portion of the nervous system, including the motor portion of the spinal cord and brain stem; the alar plate forms the dorsal portions, devoted mostly to sensory processing.

The dorsal epidermis expresses BMP4 and BMP7. The roof plate of the neural tube responds to those signals to express more BMP4 and other TGF-b signals to form a dorsal/ventral gradient among the neural tube. The notocord expresses Sonic Hedgehog (Shh). The floor plate responds to Shh by producing its own Shh and forming a gradient. These gradients allows for the differential expression of transcription factors.

 

Complexities of the model

In actuality, the folding of the neural tube is still not entirely understood and is still being studied. The simplistic model of the closure occurring in one step cranially and caudally does not explain the high frequency of neural tube defects. Proposed theories include closure of the neural tube occurs in regions, rather than entirely linearly.

 

Secondary Neurulation

 

In secondary neurulation, the neural ectoderm and some cells from the endoderm form the medullary cord. The medullary cord condenses, separates and then forms cavities. These cavities then merge to form a single tube. Secondary Neurulation occurs in the posterior section of most animals but it is better expressed in birds. Tubes from both primary and secondary neurulation eventually connect.

Early brain development

The anterior segment of the neural tube forms the three main parts of the brain: the forebrain, midbrain, and the hindbrain. Formation of these structures begins with a swelling of the neural tube in a pattern specified by Hox genes. Ion pumps are used to increase the fluid pressure within the tube and create a bulge. A blockage between the brain and the spinal cord prevents the fluid accumulation from leaking out. These brain regions further divide into subregions. The hindbrain divides into different segments called rhombomeres. Neural crest cells form ganglia above each rhombomere. The neural tube becomes the germinal neuroepithelium and serves as a source of new neurons during brain development. The brain develops from the inside-out.

Non-neural ectoderm tissue

Mesoderm surrounding the notochord at the sides will develop into the somites (future muscles, bones, and contributes to the formation of limbs of the vertebrate).

Neural crest cells

 

Masses of tissue called the neural crest that are located at the very edges of the lateral plates of the folding neural tube separate from the neural tube and migrate to become a variety of different but important cells.

Thus, nerve system originates of nerve tube and ganglious lamella. The brain and sense organs are developing from the cranial portion of nerve tube. Middle part of nerve tube and ganglionic plate give rise to spinal cord, dorsal-root ganglia (spinal ganglia), autonomic ganglia and chromaffin tissue of human body. The cells mass especially quiqly increases in the lateral part of nerve tube, whereas dorsal and ventral portions are not inlarged and have ependymal features. At this stage three zones can be recognized in the wall of nerve tube: ependyma, which covers the spinal channel, mantial layer and marginal zone. The innermost layer contains the precursors of glial ependymal cells. Population of middle zone includes two type of cells: neuroblasts and spongyoblasts, whichgive rise accordingly to nerve cells and glial ones (astrocytes and oligodendrocytes).  Later grey matter of spinal cord is developing from mantial zone and white matter from outer one.

The development of dorsal-root ganglia and peripheral autonomic ganglia begins at the same time. Ganglionic plate gives the sources for their origin – neuroblasts and glioblasts, which differentiate into neurons and mantial cells of spinal ganglia. Some cells migrate peripherally and there produce autonomic ganglia and chromaffin tissue of adrenal glands medulla.

 

THE CENTRAL NERVOUS SYSTEM

The central nervous system comprises the brain and spinal cord. It has virtually no connective tissue and is therefore a relatively soft, gel-like organ.

When sectioned, the cerebrum, cerebellum, and spinal cord show regions of white (white matter) and gray (gray matter). The differential distribution of myelin in the central nervous system is responsible for these differences: the main component of white matter is myelinated axons and the myelin-producing oligodendrocytes. White matter almost does not contaierve cells bodies.

Gray matter contains nerve cells bodies, dendrites, and the initial unmyelinated portions of axons and glial cells. This is the region where synapses occur. Gray matter is prevalent at the surface of the cerebrum and cerebellum, forming the cerebral and cerebellar cortex, whereas white matter is present in more central regions.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image008.jpg

 

Myelin sheath of the central nervous system. The same oligodendrocyte forms myelin sheaths for several (3–50) nerve fibers. In the central nervous system, processes of other cells sometimes cover the nodes of Ranvier, or there is considerable extracellular space (ES) at that point. The axolemma shows a thickening where the cell membrane of the oligodendrocyte comes into contact with it. This limits the diffusion of materials into the periaxonal space between the axon and the myelin sheath. At upper left is a surface view of the cell body of an oligodendrocyte. Cyt, cytoplasm of the oligodendrocyte.

 

BRAIN

There are anterior, middle and posterior brain. Anterior one includes large hemispheres. Brainstem includes another two portions of the brain: midbrain and posterior. The last one consists of pons, cerebellum and medulla oblongata.

Aggregates of nerve cells bodies forming islands of gray matter embedded in the white matter are called nuclei. In the cerebral cortex, the gray matter has six layers of cells with different forms and sizes. Arrangement of nerve cells in layers is termed cytoarchitecture. There are next layers: molecular, external granular, pyramidal, internal granular, ganglion and multiform.

Myeloarchitectureof large hemispheres includes 4 layers of fibers: Exner layer (up to molecular cell layer), Behterev (down) and two layers of Bajarje (up and down to the 5th layer).

Due to the structures, which are interconnecting by fibers, they are dividing into 3 groups: associative, commissural and projective. Fibers of the first group interconnect different parts of cortex of one hemisphere. Commissural ones pass through the comissura thus connecting cells of two hemispheres. Connection of large hemispheres cortex with lower portions of nervous system (subcortical nuclei and spinal cord) is realized by the last group of fibers.

Cerebral cortex is connected with different organs, due to this it is subdivided into fields of Brodman, which allows to explain dissociated disorders of sensory and motor functions in different location of structural changes (damages) of the brain.

Neurons of some regions of the cerebral cortex register afferent (sensory) impulses; in other regions, efferent (motor) neurons generate motor impulses that control voluntary movements. Cells of the cerebral cortex are related to the integration of sensory information and the initiation of voluntary motor responses.

Fields of Brodman, whose cortex is connected with sensory functions, have well prominent granular layers (so called granular cortex). External (2) and internal (4) granular layers are well developed in the audio-vestibular, visual, olfactory centers. They have a lot of cells, which makes them better visible in the slides of brain cortex.

At the same time, those parts of cortex, which are connecting with motor activity, have these layers less prominent, that’s why here the 3, 5 and 6 layers are well developed. Such agranular cortex is typical for the front of brain.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image010.jpg

The following slides show some specializations of the brain. First is an overview mid-sagittal cut of the brain, showing the many folds (or gyri) of the external cerebral cortex, and the much smaller, more delicate folds (or folia) of the cerebellar cortex seen to the left. As seen in this kind of cut, the cerebellar folia have a branching, tree-like appearance. (The brain stem is the solid-looking structure along the base of the brain, and continuous with the spinal cord at lower left.)

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image012.jpg

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image014.jpg

 

Section of cerebral cortex, showing cuts of two gyri. The pale cortex follows along the contours of the gyri. White matter (composed of nerve processes) lies below and stains a darker pink. A lot of blood vessels are seen in arachnoid of the brain. Very little cytoarchitecture is seen with H&E stain.

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image016.jpg

 

Cerebral cortex stained with silver to show silhouettes of pyramidal cells. Now each triangular cell body can be seen, as well as the ascending apical dendrite, several basal dendrites, and a very fine descending axon. These are specialized multipolar neurons with such a definite shape that they can be recognized as such.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image018.jpg

Schematic presentation of brain cortex, which shows typical pyramidal shape of cells.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image020.jpg

Associative cortex, motor cortex and sensory cortex.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image022.jpg

 

Silver-stained section of cerebral cortex showing many pyramid-shaped neurons with their processes and a few glial cells.Medium magnification.

 

Specimen illustrates the typical layered appearance of the cerebral cortex, the more detailed characteristics of each layer being as follows:

1. Plexiform (molecular) layer. This most superficial layer mainly contains dendrites and axons of cortical neurons making synapses with one another; the sparse nuclei are those of neuroglia and occasional horizontal cells of Cajal.

Horizontal cells of Cajal are small and spindle-shaped but oriented parallel to the surface. They are the least common cell type and are only found in the most superficial layer where their axons pass laterally to synapse with the dendrites of pyramidal cells.

2. Outer granular layer. A dense population of small pyramidal cells and stellate cells make up this thin layer which also contains various axons and dendrites connections from deeper layer.

Stellate (granule) cells are small neurons with a short vertical axon and several short branching dendrites giving the cell body the shape of star. With routine histological methods the cells look like small granules giving rise to their alternative name.

3. Pyramidal cell layer. Pyramidal cells of moderate size predominate in this broad layer, the cells increasing in size deeper in the layer.

Pyramidal cells have pyramid-shape cell bodies, the apex being directed towards the cortical surface. A thin axon arises from the base of the cell and passes into the underlying white matter, though in the case of small superficially located cells, the axon may synapse in the deep layers of the cortex. From the apex, a thick branching dendrite passes towards the surface where it has a prolific array of fine dendrites branches. In addition, short dendrites arise from the edges of the base and ramify laterally. The size oh pyramidal cells varies from small to large, the smallest tending to lie more superficially.

4. Inner granular layer. This narrow layer consists mainly of densely packed stellate cells of small size.

5. Ganglionic layer. Large pyramidal cells and smaller numbers of stellate cells and cells of Martinotti make up this layer, the name of the layer originating from the huge pyramidal (ganglion) Betz cells of the motor cortex. Each pyramidal cell is oriented in the layer with apex up to the surface of cortex. The basic part of cell lies deeply. Dendrites arise from the apex of the cell and from the back surfaces. Axon begins from the plate lower surface of the cell and pass down to the white matter.

6. Multiform cell layer. So named on account of the wide variety of differing morphological forms found in this layer, the layer contains numerous small pyramidal cells and cells of Martinotti, as well as stellate cells especially superficially, and fusiform cells in the deeper part.

Cells of Martinotti are small polygonal cells with a few short dendrites and the axon extending toward the surface and bifurcating to run horizontally, most commonly in the most superficial layer.

Fusiform cells are spindle-shaped cells oriented at right angels to the surface. The axon arises from the side of the cell body and passes superficially. Dendrites extend from each end of the cell body branching so as to pass vertically into deeper and more superficial layers.

Huge pyramidal cells are interconnected between themselves in one and two hemispheres. Their axons produce special cortico-cortical fibers. This allows to identify structural unit of large brain cortex – modul– cylinder  aroundcortico-cortical fiber (d 300 mkm),  which includes all nearest nerve cells connecting with this fiber.

In addition to neurons, the cortex contains supporting neuroglial cells i.e. astrocytes, oligodendrocytes and microglia.

 

CEREBELLUM

The cerebellum is an important part of the brain and the highest center of balance and coordination of movements of the body, it promoting muscular tension. It is connected with the brain column by afferent and efferent conductive ways, they forming three pairs of cerebellar limbs. In the nuclei of the column switching of the nervous impulses takes place, they coming from the spinal cord, spinal ganglions to the cerebral hemispheres and the cerebellum and in the opposite direction from the column to the cortex. Functional impairment of the cerebellum may occur in intoxication, for example, alcohol intoxication, infections, and traumas. Cerebral column hemorrhages can result in impairments of the subcortical centers, including respiratory, vasomotor centers, with severe consequences for the patient.

The cerebellar cortex has three layers: an outer molecular layer, a central layer of large Purkinje cells, and an inner granular layer. The Purkinje cells have huge cell bodies, a relatively fine axon extending down through the granule cell layer, and their dendrites are highly developed, assuming the aspect of a fan. These dendrites occupy most of the molecular layer and are the reason for the sparseness of nuclei. Special gliocytes (astrocytes) – lophogliocytes lie in this layer. They have a lot of processes, which accompanied dendrites of Purkinje cells, supporting and protect them.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image024.jpg

Scheme of Purkinje cell

The cerebellum (Latin for little brain) is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses,but its movement-related functions are the most solidly established. The cerebellum does not initiate movement, but it contributes to coordination, precision, and accurate timing. It receives input from sensory systems of the spinal cord and from other parts of the brain, and integrates these inputs to fine tune motor activity. Cerebellar damage does not cause paralysis, but instead produces disorders in fine movement, equilibrium, posture, and motor learning.

Anatomically, the cerebellum has the appearance of a separate structure attached to the bottom of the brain, tucked underneath the cerebral hemispheres. Its surface is covered with finely spaced parallel grooves, in striking contrast to the broad irregular convolutions of the cerebral cortex. These parallel grooves conceal the fact that the cerebellum is actually a continuous thin layer of tissue (the cerebellar cortex), tightly folded in the style of an accordion. Within this thin layer are several types of neurons with a highly regular arrangement, the most important being Purkinje cells and granule cells. This complex neural network gives rise to a massive signal-processing capability, but almost all of its output is directed to a set of small deep cerebellar nuclei lying in the interior of the cerebellum.

In addition to its direct role in motor control, the cerebellum also is necessary for several types of motor learning, most notably learning to adjust to changes in sensorimotor relationships. Several theoretical models have been developed to explain sensorimotor calibration in terms of synaptic plasticity within the cerebellum. Most of them derive from early models formulated by David Marr and James Albus, which were motivated by the observation that each cerebellar Purkinje cell receives two dramatically different types of input: on one hand, thousands of inputs from parallel fibers, each individually very weak; on the other hand, input from one single climbing fiber, which is, however, so strong that a single climbing fiber action potential will reliably cause a target Purkinje cell to fire a burst of action potentials. The basic concept of the Marr-Albus theory is that the climbing fiber serves as a “teaching signal”, which induces a long-lasting change in the strength of synchronously activated parallel fiber inputs. Observations of long-term depression in parallel fiber inputs have provided support for theories of this type, but their validity remains controversial.

At the level of large scale anatomy, the cerebellum consists of a tightly folded and crumpled layer of cortex, with white matter underneath, several deep nuclei embedded in the white matter, and a fluid-filled ventricle at the base. At the microscopic level, each part of the cortex consists of the same small set of neuronal elements, laid out with a highly stereotyped geometry. At an intermediate level, the cerebellum and its auxiliary structures can be decomposed into several hundred or thousand independently functioning modules called “microzones” or “microcompartments”.

http://upload.wikimedia.org/wikipedia/commons/thumb/1/15/Human_cerebellum_anterior_view_description.JPG/220px-Human_cerebellum_anterior_view_description.JPG

 

Anterior view of the human cerebellum, with numbers indicating salient landmarks

The cerebellum is located at the bottom of the brain, with the large mass of the cerebral cortex above it and the portion of the brainstem called the pons in front of it.It is separated from the overlying cerebrum by a layer of leathery dura mater; all of its connections with other parts of the brain travel through the pons. Anatomists classify the cerebellum as part of the metencephalon, which also includes the pons; the metencephalon is the upper part of the rhombencephalon or “hindbrain”. Like the cerebral cortex, the cerebellum is divided into two hemispheres; it also contains a narrow midline zone called the vermis. A set of large folds is, by convention, used to divide the overall structure into 10 smaller “lobules”. Because of its large number of tiny granule cells, the cerebellum contains more neurons than the rest of the brain put together, but it takes up only 10% of total brain volume.The number of neurons in the cerebellum is related to the number of neurons in the neocortex. There are about 3.6 times as many neurons in the cerebellum as ieocortex, a number that is conserved across many different mammalian species.

The unusual surface appearance of the cerebellum conceals the fact that most of its volume is made up of a very tightly folded layer of gray matter, the cerebellar cortex. It has been estimated that, if the human cerebellar cortex were completely unfolded, it would give rise to a layer of neural tissue about 1 meter long and averaging 5 centimeters wide — a total surface area of about 500 square cm, packed within a volume of dimensions 6 cm × 5 cm × 10 cm. Underneath the gray matter of the cortex lies white matter, made up largely of myelinated nerve fibers running to and from the cortex. Embedded within the white matter — which is sometimes called the arbor vitae (Tree of Life) because of its branched, tree-like appearance in cross-section — are four deep cerebellar nuclei, composed of gray matter.

Based on surface appearance, three lobes can be distinguished in the cerebellum, called the flocculonodular lobe, anterior lobe (above the primary fissure), and posterior lobe (below the primary fissure). These lobes divide the cerebellum from rostral to caudal (in humans, top to bottom). In terms of function, however, there is a more important distinction along the medial-to-lateral dimension. Leaving out the flocculonodular part, which has distinct connections and functions, the cerebellum can be parsed functionally into a medial sector called the spinocerebellum and a larger lateral sector called the cerebrocerebellum.A narrow strip of protruding tissue along the midline is called the vermis (Latin for “worm”).

The smallest region, the flocculonodular lobe, is often called the vestibulocerebellum. It is the oldest part in evolutionary terms (archicerebellum) and participates mainly in balance and spatial orientation; its primary connections are with the vestibular nuclei, although it also receives visual and other sensory input. Damage to it causes disturbances of balance and gait.

The medial zone of the anterior and posterior lobes constitutes the spinocerebellum, also known as paleocerebellum. This sector of the cerebellum functions mainly to fine-tune body and limb movements. It receives proprioception input from the dorsal columns of the spinal cord (including the spinocerebellar tract) and from the trigeminal nerve, as well as from visual and auditory systems. It sends fibres to deep cerebellar nuclei that, in turn, project to both the cerebral cortex and the brain stem, thus providing modulation of descending motor systems.

The lateral zone, which in humans is by far the largest part, constitutes the cerebrocerebellum, also known as neocerebellum. It receives input exclusively from the cerebral cortex (especially the parietal lobe) via the pontine nuclei (forming cortico-ponto-cerebellar pathways), and sends output mainly to the ventrolateralthalamus (in turn connected to motor areas of the premotor cortex and primary motor area of the cerebral cortex) and to the red nucleus. There is disagreement about the best way to describe the functions of the lateral cerebellum: It is thought to be involved in planning movement that is about to occur, in evaluating sensory information for action, and in a number of purely cognitive functions as well, such as determining the verb which best fits with a certaioun (as in ‘sit’ for ‘chair’).

http://upload.wikimedia.org/wikipedia/commons/thumb/7/72/CerebCircuit.png/275px-CerebCircuit.png

Microcircuitry of the cerebellum. (+): excitatory; (-): inhibitory; MF: Mossy fiber; DCN: Deep cerebellar nuclei; IO: Inferior olive; CF: Climbing fiber; GC: Granule cell; PF: Parallel fiber; PC: Purkinje cell; GgC: Golgi cell; SC: Stellate cell; BC: Basket cell

Two types of neuron play dominant roles in the cerebellar circuit: Purkinje cells and granule cells. Three types of axons also play dominant roles: mossy fibers and climbing fibers (which enter the cerebellum from outside), and parallel fibers (which are the axons of granule cells). There are two main pathways through the cerebellar circuit, originating from mossy fibers and climbing fibers, both eventually terminating in the deep cerebellar nuclei.

Mossy fibers project directly to the deep nuclei, but also give rise to the pathway: mossy fiber → granule cells → parallel fibers → Purkinje cells → deep nuclei. Climbing fibers project to Purkinje cells and also send collaterals directly to the deep nuclei. The mossy fiber and climbing fiber inputs each carry fiber-specific information; the cerebellum also receives dopaminergic, serotonergic, noradrenergic, and cholinergic inputs that presumably perform global modulation.

The cerebellar cortex is divided into three layers. At the bottom lies the thick granular layer, densely packed with granule cells, along with interneurons, mainly Golgi cells but also including Lugaro cells and unipolar brush cells. In the middle lies the Purkinje layer, a narrow zone that contains only the cell bodies of Purkinje cells. At the top lies the molecular layer, which contains the flattened dendritic trees of Purkinje cells, along with the huge array of parallel fibers penetrating the Purkinje cell dendritic trees at right angles. This outermost layer of the cerebellar cortex also contains two types of inhibitory interneurons, stellate cells, and basket cells. Both stellate and basket cells form GABAergic synapses onto Purkinje cell dendrites.

Purkinje cells are among the most distinctive neurons in the brain, and also among the earliest types to be recognized — they were first described by the Czech anatomist Jan Evangelista Purkyně in 1837. They are distinguished by the shape of the dendritic tree: The dendrites branch very profusely, but are severely flattened in a plane perpendicular to the cerebellar folds. Thus, the dendrites of a Purkinje cell form a dense planar net, through which parallel fibers pass at right angles. The dendrites are covered with dendritic spines, each of which receives synaptic input from a parallel fiber. Purkinje cells receive more synaptic inputs than any other type of cell in the brain — estimates of the number of spines on a single human Purkinje cell run as high as 200,000. The large, spherical cell bodies of Purkinje cells are packed into a narrow layer (one cell thick) of the cerebellar cortex, called the Purkinje layer. After emitting collaterals that innervate nearby parts of the cortex, their axons travel into the deep cerebellar nuclei, where they make on the order of 1,000 contacts each with several types of nuclear cells, all within a small domain. Purkinje cells use GABA as their neurotransmitter, and therefore exert inhibitory effects on their targets.

Purkinje cells form the heart of the cerebellar circuit, and their large size and distinctive activity patterns have made it relatively easy to study their response patterns in behaving animals using extracellular recording techniques. Purkinje cells normally emit action potentials at a high rate even in the absence of synaptic input. In awake, behaving animals, mean rates averaging around 40 Hz are typical. The spike trains show a mixture of what are called simple and complex spikes. A simple spike is a single action potential followed by a refractory period of about 10 ms; a complex spike is a stereotyped sequence of action potentials with very short inter-spike intervals and declining amplitudes. Physiological studies have shown that complex spikes (which occur at baseline rates around 1 Hz and never at rates much higher than 10 Hz) are reliably associated with climbing fiber activation, while simple spikes are produced by a combination of baseline activity and parallel fiber input. Complex spikes are often followed by a pause of several hundred milliseconds during which simple spike activity is suppressed.

The outermost molecular layer has two principal types of cells. They are basket and stellate cells. Basket cells are middle-sized multipolar neurons whose bodies lie in the lower part of this layer, close to ganglion layer. Their axons move to the bodies of Purkinje cells and turn around them many times, producing special “basket”. Large stellate cells are very similar; their perikaryons have the same location. Small stellate cells of cerebellar molecular layer are smaller, lie upper and their axons are connecting with dendrites of Purkinje cells in opposite to basket and large stellate cells.

The granular layer is formed by very small neurons (the smallest in the body), which are compactly disposed, in contrast to the less cell-dense molecular layer. There4 are 4 types of cells here. Corn cells are small multipolar neurons whose axons pass up to the molecular layer, making there collaterals parallely to the surface of cortex, and connecting with dendrites of basket, stellate and Purkinje cells. Corn cells are the only cells which transmit the stimuli to the cerebellar cortex. Two types of Golgi cells (with short and long axons) and horizontal cells perform the inhibiting functions.

Granule cells

Cerebellar granule cells, in contrast to Purkinje cells, are among the smallest neurons in the brain. They are also easily the most numerous neurons in the brain: In humans, estimates of their total number average around 50 billion, which means that about 3/4 of the brain’s neurons are cerebellar granule cells. Their cell bodies are packed into a thick layer at the bottom of the cerebellar cortex. A granule cell emits only four to five dendrites, each of which ends in an enlargement called a dendritic claw. These enlargements are sites of excitatory input from mossy fibers and inhibitory input from Golgi cells.

http://upload.wikimedia.org/wikipedia/commons/thumb/0/0c/Parallel-fibers.png/220px-Parallel-fibers.png

Granule cells, parallel fibers, and Purkinje cells with flattened dendritic trees

The thin, unmyelinated axons of granule cells rise vertically to the upper (molecular) layer of the cortex, where they split in two, with each branch traveling horizontally to form a parallel fiber; the splitting of the vertical branch into two horizontal branches gives rise to a distinctive “T” shape. A parallel fiber runs for an average of 3 mm in each direction from the split, for a total length of about 6 mm (about 1/10 of the total width of the cortical layer). As they run along, the parallel fibers pass through the dendritic trees of Purkinje cells, contacting one of every 3–5 that they pass, making a total of 80–100 synaptic connections with Purkinje cell dendritic spines. Granule cells use glutamate as their neurotransmitter, and therefore exert excitatory effects on their targets.

Granule cells receive all of their input from mossy fibers, but outnumber them 200 to 1 (in humans). Thus, the information in the granule cell population activity state is the same as the information in the mossy fibers, but recoded in a much more expansive way. Because granule cells are so small and so densely packed, it has been very difficult to record their spike activity in behaving animals, so there is little data to use as a basis of theorizing. The most popular concept of their function was proposed by David Marr, who suggested that they could encode combinations of mossy fiber inputs. The idea is that with each granule cell receiving input from only 4–5 mossy fibers, a granule cell would not respond if only a single one of its inputs were active, but would respond if more than one were active. This combinatorial coding scheme would potentially allow the cerebellum to make much finer distinctions between input patterns than the mossy fibers alone would permit.

So, only Purkinje and corn cells are excitatory neurons in cerebellar cortex all the other neurons have inhibiting functions.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image026.jpg

Scheme of nerve cells location in cerebellar cortex.

 

Conductive system of cerebellum

 

Cerebellum has coordinative function, it regulates balance and muscular tension, that’s why it has a lot of different connections.

Afferent and efferent fibers of cerebellum comprise the nerve fibers, which connect the cerebellar cortex with other structures of nerve system.

 

Afferent fibers of cerebellum include mosslike and climbing fibers.

Mosslike fibers arise from olives (tr. olivocerebellaris) and cerebellar pons (tr. pontocerebellaris), transmitting stimuli to dendrites of corn cells. Meshwork of these fibers gives name to this structure.

Climbing fibers originate from spinal cord (tr. spinocerebellaris) and vestibular nuclei (tr. vestibulocerebellaris), cross the granular layer and transmit the nerve impulses to the dendrites of Purkinje cells.

Mossy fibers

Mossy fibers enter the granular layer from their points of origin, many arising from the pontine nuclei, others from the spinal cord, vestibular nuclei, etc. In the human cerebellum, the total number of mossy fibers has been estimated at about 200 million. These fibers form excitatory synapses with the granule cells and the cells of the deep cerebellar nuclei. Within the granular layer, a mossy fiber generates a series of enlargements called rosettes. The contacts between mossy fibers and granule cell dendrites take place within structures called glomeruli. Each glomerulus has a mossy fiber rosette at its center, and up to 20 granule cell dendritic claws contacting it. Terminals from Golgi cells infiltrate the structure and make inhibitory synapses onto the granule cell dendrites. The entire assemblage is surrounded by a sheath of glial cells. Each mossy fiber sends collateral branches to several cerebellar folia, generating a total of 20–30 rosettes; thus a single mossy fiber makes contact with an estimated 400–600 granule cells.

Climbing fibers

Purkinje cells also receive input from the inferior olivary nucleus (IO) on the contralateral side of the brainstem, via climbing fibers. Although the IO lies in the medulla oblongata, and receives input from the spinal cord, brainstem, and cerebral cortex, its output goes entirely to the cerebellum. A climbing fiber gives off collaterals to the deep cerebellar nuclei before entering the cerebellar cortex, where it splits into about 10 terminal branches, each of which innervates a single Purkinje cell. In striking contrast to the 100,000-plus inputs from parallel fibers, each Purkinje cell receives input from exactly one climbing fiber; but this single fiber “climbs” the dendrites of the Purkinje cell, winding around them and making a total of up to 300 synapses as it goes. The net input is so strong that a single action potential from a climbing fiber is capable of producing an extended complex spike in the Purkinje cell: a burst of several spikes in a row, with diminishing amplitude, followed by a pause during which activity is suppressed. The climbing fiber synapses cover the cell body and proximal dendrites; this zone is devoid of parallel fiber inputs.

Climbing fibers fire at low rates, but a single climbing fiber action potential induces a burst of several action potentials in a target Purkinje cell (a complex spike). The contrast between parallel fiber and climbing fiber inputs to Purkinje cells (over 100,000 of one type versus exactly one of the other type) is perhaps the most provocative feature of cerebellar anatomy, and has motivated much of the theorizing. In fact, the function of climbing fibers is the most controversial topic concerning the cerebellum. There are two schools of thought, one following Marr and Albus in holding that climbing fiber input serves primarily as a teaching signal, the other holding that its function is to shape cerebellar output directly. Both views have been defended in great length iumerous publications. In the words of one review, “In trying to synthesize the various hypotheses on the function of the climbing fibers, one has the sense of looking at a drawing by Escher. Each point of view seems to account for a certain collection of findings, but when one attempts to put the different views together, a coherent picture of what the climbing fibers are doing does not appear. For the majority of researchers, the climbing fibers signal errors in motor performance, either in the usual manner of discharge frequency modulation or as a single announcement of an ‘unexpected event’. For other investigators, the message lies in the degree of ensemble synchrony and rhythmicity among a population of climbing fibers.”

The efferent fibers of cerebellum consists mainly of Purkinje cells axons, which move to subcortical nuclei (n.n. dentatus, lentiformis and so on)

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image028.jpg

 

Section of cerebellar cortex, showing several folia. Each folium has a central core of bright blue white matter, consisting of nerve processes entering and leaving the superficial cortex. The cortex has an external pale layer and a darker staining granular layer beneath it. Large Purkinje cells lie in a row between these two layers but are not visible at this magnification.

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image030.jpg

 

Higher magnification of cerebellar cortex, showing the row of large Purkinje cells lying between the outer and inner cortical layers. The stubs of the dendritic trees of the Purkinje cells look rather like “antlers” arising from the cell bodies. Very complex dendritic brunching actually extend throughout the molecular layer above the Purkinje c ells. A single axon leaves each Purkinje cell at its oval base and descends through the granular layer to deeper relay stations within the brain. Again, these are neurons with a very distinctive shape.

Photomicrograph of the cerebellum. The staining procedure used (H&E) does not reveal the unusually large dendritic arborization of the Purkinje cell. Low magnification.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image032.jpg

 

Section of the cerebellum with distinct Purkinje cells. One Purkinje cell shows part of its rich dendritic arborization. H&E stain. Medium magnification.

The deep nuclei of the cerebellum are clusters of gray matter lying within the white matter at the core of the cerebellum. They are, with the minor exception of the nearby vestibular nuclei, the sole sources of output from the cerebellum. These nuclei receive collateral projections from mossy fibers and climbing fibers, as well as inhibitory input from the Purkinje cells of the cerebellar cortex. The three nuclei (dentate, interpositus, and fastigial) each communicate with different parts of the brain and cerebellar cortex. The fastigial and interpositus nuclei belong to the spinocerebellum. The dentate nucleus, which in mammals is much larger than the others, is formed as a thin, convoluted layer of gray matter, and communicates exclusively with the lateral parts of the cerebellar cortex. The flocculonodular lobe is the only part of the cerebellar cortex that does not project to the deep nuclei — its output goes to the vestibular nuclei instead.

The majority of neurons in the deep nuclei have large cell bodies and spherical dendritic trees with a radius of about 400 μm, and use glutamate as their neurotransmitter. These cells project to a variety of targets outside the cerebellum. Intermixed with them is a lesser number of small cells, which use GABA as neurotransmitter and project exclusively to the inferior olivary nucleus, the source of climbing fibers. Thus, the nucleo-olivary projection provides an inhibitory feedback to match the excitatory projection of climbing fibers to the nuclei. There is evidence that each small cluster of nuclear cells projects to the same cluster of olivary cells that send climbing fibers to it; there is strong and matching topography in both directions.

When a Purkinje cell axon enters one of the deep nuclei, it branches to make contact with both large and small nuclear cells, but the total number of cells contacted is only about 35 (in cats). On the converse, a single deep nuclear cell receives input from approximately 860 Purkinje cells (again in cats).

http://upload.wikimedia.org/wikipedia/commons/thumb/f/f9/Microzone.svg/250px-Microzone.svg.png

Schematic illustration of the structure of zones and microzones in the cerebellar cortex

From the viewpoint of gross anatomy, the cerebellar cortex appears to be a homogeneous sheet of tissue, and, from the viewpoint of microanatomy, all parts of this sheet appear to have the same internal structure. There are, however, a number of respects in which the structure of the cerebellum is compartmentalized. There are large compartments that are generally known as zones; these can be decomposed into smaller compartments known as microzones.

The first indications of compartmental structure came from studies of the receptive fields of cells in various parts of the cerebellum cortex. Each body part maps to specific points in the cerebellum, but there are numerous repetitions of the basic map, forming an arrangement that has been called “fractured somatotopy”.A clearer indication of compartmentalization is obtained by immunostaining the cerebellum for certain types of protein. The best-known of these markers are called “zebrins”, because staining for them gives rise to a complex pattern reminiscent of the stripes on a zebra. The stripes generated by zebrins and other compartmentalization markers are oriented perpendicular to the cerebellar folds — that is, they are narrow in the mediolateral direction, but much more extended in the longitudinal direction. Different markers generate different sets of stripes, and the widths and lengths vary as a function of location, but they all have the same general shape.

Oscarsson in the late 1970s proposed that these cortical zones can be partitioned into smaller units called microzones. A microzone is defined as a group of Purkinje cells all having the same somatotopic receptive field. Microzones were found to contain on the order of 1000 Purkinje cells each, arranged in a long, narrow strip, oriented perpendicular to the cortical folds. Thus, as the adjoining diagram illustrates, Purkinje cell dendrites are flattened in the same direction as the microzones extend, while parallel fibers cross them at right angles.

It is not only receptive fields that define the microzone structure: The climbing fiber input from the inferior olivary nucleus is equally important. The branches of a climbing fiber (usually numbering about 10) usually innervate Purkinje cells belonging to the same microzone. Moreover, olivary neurons that send climbing fibers to the same microzone tend to be coupled by gap junctions, which synchronize their activity, causing Purkinje cells within a microzone to show correlated complex spike activity on a millisecond time scale. Also, the Purkinje cells belonging to a microzone all send their axons to the same small cluster of output cells within the deep cerebellar nuclei. Finally, the axons of basket cells are much longer in the longitudinal direction than in the mediolateral direction, causing them to be confined largely to a single microzone. The consequence of all this structure is that cellular interactions within a microzone are much stronger than interactions between different microzones.

In 2005, Richard Apps and Martin Garwicz summarized evidence that microzones themselves form part of a larger entity they call a multizonalmicrocomplex. Such a microcomplex includes several spatially separated cortical microzones, all of which project to the same group of deep cerebellar neurons, plus a group of coupled olivary neurons that project to all of the included microzones as well as to the deep nuclear area.

The strongest clues to the function of the cerebellum have come from examining the consequences of damage to it. Animals and humans with cerebellar dysfunction show, above all, problems with motor control, on the side of the body ipsilateral to the damaged cerebellum. They continue to be able to generate motor activity, but it loses precision, producing erratic, uncoordinated, or incorrectly timed movements. A standard test of cerebellar function is to reach with the tip of the finger for a target at arm’s length: A healthy person will move the fingertip in a rapid straight trajectory, whereas a person with cerebellar damage will reach slowly and erratically, with many mid-course corrections. Deficits ion-motor functions are more difficult to detect. Thus, the general conclusion reached decades ago is that the basic function of the cerebellum is not to initiate movements, or to decide which movements to execute, but rather to calibrate the detailed form of a movement.

Prior to the 1990s, the function of the cerebellum was almost universally believed to be purely motor-related, but newer findings have brought that view strongly into question. Functional imaging studies have shown cerebellar activation in relation to language, attention, and mental imagery; correlation studies have shown interactions between the cerebellum and non-motoric areas of the cerebral cortex; and a variety of non-motor symptoms have been recognized in people with damage that appears to be confined to the cerebellum. In particular, the Cerebellar Cognitive Affective Syndrome has been described in adults and children.

Kenji Doya has argued that the function of the cerebellum is best understood not in terms of what behaviors it is involved in but rather in terms of what neural computations it performs; the cerebellum consists of a large number of more or less independent modules, all with the same geometrically regular internal structure, and therefore all, it is presumed, performing the same computation. If the input and output connections of a module are with motor areas (as many are), then the module will be involved in motor behavior; but, if the connections are with areas involved ion-motor cognition, the module will show other types of behavioral correlates. The cerebellum, Doya proposes, is best understood as a device for supervised learning, in contrast to the basal ganglia, which perform reinforcement learning, and the cerebral cortex, which performs unsupervised learning.

The comparative simplicity and regularity of the cerebellar anatomy led to an early hope that it might imply a similar simplicity of computational function, as expressed in one of the first books on cerebellar electrophysiology, The Cerebellum as a Neuronal Machine by John C. Eccles, Masao Ito, and Janos Szentágothai. Although a full understanding of cerebellar function has remained elusive, at least four principles have been identified as important: (1) feedforward processing, (2) divergence and convergence, (3) modularity, and (4) plasticity.

1. Feedforward processing: The cerebellum differs from most other parts of the brain (especially the cerebral cortex) in that the signal processing is almost entirely feedforward – that is, signals move unidirectionally through the system from input to output, with very little recurrent internal transmission. The small amount of recurrence that does exist consists of mutual inhibition; there are no mutually excitatory circuits. This feedforward mode of operation means that the cerebellum, in contrast to the cerebral cortex, cannot generate self-sustaining patterns of neural activity. Signals enter the circuit, are processed by each stage in sequential order, and then leave. As Eccles, Ito, and Szentágothai wrote, “This elimination in the design of all possibility of reverberatory chains of neuronal excitation is undoubtedly a great advantage in the performance of the cerebellum as a computer, because what the rest of the nervous system requires from the cerebellum is presumably not some output expressing the operation of complex reverberatory circuits in the cerebellum but rather a quick and clear response to the input of any particular set of information.”

2. Divergence and convergence: In the human cerebellum, information from 200 million mossy fiber inputs is expanded to 40 billion granule cells, whose parallel fiber outputs then converge onto 15 million Purkinje cells. Because of the way that they are lined up longitudinally, the 1000 or so Purkinje cells belonging to a microzone may receive input from as many as 100 million parallel fibers, and focus their own output down to a group of less than 50 deep nuclear cells. Thus, the cerebellar network receives a modest number of inputs, processes them very extensively through its rigorously structured internal network, and sends out the results via a very limited number of output cells.

3. Modularity: The cerebellar system is functionally divided into more or less independent modules, which probably number in the hundreds to thousands. All modules have a similar internal structure, but different inputs and outputs. A module (a multizonalmicrocompartment in the terminology of Apps and Garwicz) consists of a small cluster of neurons in the inferior olivary nucleus, a set of long narrow strips of Purkinje cells in the cerebellar cortex (microzones), and a small cluster of neurons in one of the deep cerebellar nuclei. Different modules share input from mossy fibers and parallel fibers, but in other respects they appear to function independently — the output of one module does not appear to significantly influence the activity of other modules.

4. Plasticity: The synapses between parallel fibers and Purkinje cells, and the synapses between mossy fibers and deep nuclear cells, are both susceptible to modification of their strength. In a single cerebellar module, input from as many as a billion parallel fibers converges onto a group of less than 50 deep nuclear cells, and the influence of each parallel fiber on those nuclear cells is adjustable. This arrangement gives tremendous flexibility for fine-tuning the relationship between cerebellar inputs and outputs.

There is considerable evidence that the cerebellum plays an essential role in some types of motor learning. The tasks where the cerebellum most clearly comes into play are those in which it is necessary to make fine adjustments to the way an action is performed. There has, however, been much dispute about whether learning takes place within the cerebellum itself, or whether it merely serves to provide signals that promote learning in other brain structures. Most theories that assign learning to the circuitry of the cerebellum are derived from early ideas of David Marr and James Albus, who postulated that climbing fibers provide a teaching signal that induces synaptic modification in parallel fiberPurkinje cell synapses. Marr assumed that climbing fiber input would cause synchronously activated parallel fiber inputs to be strengthened. Most later cerebellar-learning models, however, have followed Albus in assuming that climbing fiber activity would be an error signal, and would cause synchronously activated parallel fiber inputs to be weakened. Some of these later models, such as the Adaptive Filter model of Fujita made attempts to understand cerebellar function in terms of optimal control theory.

The idea that climbing fiber activity functions as an error signal has been examined in many experimental studies, with some supporting it but others casting doubt. In a pioneering study by Gilbert and Thach from 1977, Purkinje cells from monkeys learning a reaching task showed increased complex spike activity — which is known to reliably indicate activity of the cell’s climbing fiber input — during periods when performance was poor. Several studies of motor learning in cats observed complex spike activity when there was a mismatch between an intended movement and the movement that was actually executed. Studies of the vestibulo-ocular reflex (which stabilizes the visual image on the retina when the head turns) found that climbing fiber activity indicated “retinal slip”, although not in a very straightforward way.

One of the most extensively studied cerebellar learning tasks is the eyeblink conditioning paradigm, in which a neutral conditioned stimulus such as a tone or a light is repeatedly paired with an unconditioned stimulus, such as an air puff, that elicits a blink response. After such repeated presentations of the CS and US, the CS will eventually elicit a blink before the US, a conditioned response or CR. Experiments showed that lesions localized either to a specific part of the interpositus nucleus (one of the deep cerebellar nuclei) or to a few specific points in the cerebellar cortex would abolish learning of a correctly timed blink response. If cerebellar outputs are pharmacologically inactivated while leaving the inputs and intracellular circuits intact, learning takes place even while the animal fails to show any response, whereas, if intracerebellar circuits are disrupted, no learning takes place — these facts taken together make a strong case that the learning, indeed, occurs inside the cerebellum.

http://upload.wikimedia.org/wikipedia/commons/thumb/6/63/Model_of_Cerebellar_Perceptron.jpg/220px-Model_of_Cerebellar_Perceptron.jpg

Model of a cerebellar perceptron, as formulated by James Albus

The large base of knowledge about the anatomical structure and behavioral functions of the cerebellum have made it a fertile ground for theorizing — there are perhaps more theories of the function of the cerebellum than of any other part of the brain. The most basic distinction among them is between “learning theories” and “performance theories” — that is, theories that make use of synaptic plasticity within the cerebellum to account for its role in learning, versus theories that account for aspects of ongoing behavior on the basis of cerebellar signal processing. Several theories of both types have been formulated as mathematical models and simulated using computers.

Perhaps the earliest “performance” theory was the “delay line” hypothesis of Valentino Braitenberg. The original theory put forth by Braitenberg and Atwood in 1958 proposed that slow propagation of signals along parallel fibers imposes predictable delays that allow the cerebellum to detect time relationships within a certain window. Experimental data did not support the original form of the theory, but Braitenberg continued to argue for modified versions. The hypothesis that the cerebellum functions essentially as a timing system has also been advocated by Richard Ivry. Another influential “performance” theory is the Tensor Network Theory of Pellionisz and Llinás, which provided an advanced mathematical formulation of the idea that the fundamental computation performed by the cerebellum is to transform sensory into motor coordinates.

Theories in the “learning” category almost all derive from early publications by David Marr and James Albus. Marr’s 1969 paper proposed that the cerebellum is a device for learning to associate elemental movements encoded by climbing fibers with mossy fiber inputs that encode the sensory context. Albus proposed that a cerebellar Purkinje cell functions as a perceptron, a neurally inspired abstract learning device. The most basic difference between the Marr and Albus theories is that Marr assumed that climbing fiber activity would cause parallel fiber synapses to be strengthened, whereas Albus proposed that they would be weakened. Albus also formulated his version as a software algorithm he called a CMAC (Cerebellar Model Articulation Controller), which has been tested in a number of applications.

The most salient symptoms of cerebellar dysfunction are motor-related — the specific symptoms depend on which part of the cerebellum is involved and how it is disrupted. Damage to the flocculonodular lobe (the vestibular part) may show up as a loss of equilibrium and, in particular, an altered walking gait, with a wide stance that indicates difficulty in balancing. Damage to the lateral zone, or the cerebrocerebellum, results in problems with skilled voluntary and planned movements. This can cause errors in the force, direction, speed and amplitude of movements. Some manifestations include hypotonia (decreased muscle tone), dysarthria (problems with speech articulation), dysmetria (problems judging distances or ranges of movement), dysdiadochokinesia (inability to perform rapid alternating movements), impaired check reflex or rebound phenomenon, and tremors (involuntary movement caused by alternating contractions of opposing muscle groups). Damage to the midline portion may disrupt whole-body movements, whereas damage localized more laterally is more likely to disrupt fine movements of the hands or limbs. Damage to the upper part of the cerebellum tends to cause gait impairments and other problems with leg coordination; damage to the lower part is more likely to cause uncoordinated or poorly aimed movements of the arms and hands, as well as difficulties in speed. This complex of motor symptoms is called “ataxia”. To identify cerebellar problems, the neurological examination includes assessment of gait (a broad-based gait being indicative of ataxia), finger-pointing tests and assessment of posture. If cerebellar dysfunction is indicated, a magnetic resonance imaging scan can be used to obtain a detailed picture of any structural alterations that may exist.

The human cerebellum changes with age. These changes may differ from those of other parts of the brain, for example the gene expression pattern in the human cerebellum shows less age-related alteration than in the cerebral cortex.[35] Some studies have reported reductions iumbers of cells or volume of tissue, but the amount of data relating to this question is not very large.

Compound reflex arc

Brain is involved iervous activity, being included in compound reflex arc.

A lot of nerve cells which lie in the spinal cord and brain participate in the passage of nerve impulses, they are located between sensory and motor neurons.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image034.jpg

 

Schematic representation of a nerve and a reflex arc. In this example, the sensory stimulus starts in the skin and passes to the spinal cord via the dorsal root ganglion. The sensory stimulus is transmitted to an interneuron that activates a motor neuron that innervates skeletal muscle. Examples of the operation of this reflex are withdrawal of the finger from a hot surface and the knee-jerk reflex.

 

MENINGES

The central nervous system is protected by the skull and the vertebral column. It is also encased in membranes of connective tissue called the meninges. Starting with the outermost layer, the meninges are the dura mater, arachnoid, and pia mater. The arachnoid and the pia mater are linked together and are often considered a single membrane called the pia-arachnoid.

 

Dura Mater

 

The dura mater is the external layer (meninx) and is composed of dense connective tissue continuous with the periosteum of the skull. The dura mater that envelops the spinal cord is separated from the perios­teum of the vertebrae by the epidural space, which contains thin-walled veins, loose connective tissue, and adipose tissue.

The dura mater is always separated from the arachnoid by the thin subdural space. The internal surface of all dura mater, as well as its external sur­face in the spinal cord, is covered by simple squamous epithelium of mesenchymal origin.

 

Arachnoid

 

The arachnoid (Gr. arachnoeides, cobweb-like) has two components: a layer in contact with the dura mater, and a system of trabeculae connecting the layer with the pia mater. The cavities between the trabeculae form the subarachnoid space, which is filled with cerebrospinal fluid and is completely separated from the subdural space. This space forms a hydraulic cushion that protects the central nervous system from trauma. The subarachnoid space communicates with the ventricles of the brain.

The arachnoid is composed of connective tissue devoid of blood vessels. Its surfaces are covered by the same type of simple squamous epithelium that covers the dura mater. Since the arachnoid has fewer trabeculae in the spinal cord, it can be more cleanly distinguished from the pia mater in that area.

In some areas, the arachnoid perforates the dura mater, forming protrusions that terminate in venous sinuses in the dura mater. These protrusions, which are covered by endothelial cells of the veins, are called arachnoid villi. Their function is to reabsorb cerebrospinal fluid into the blood of the venous sinuses.

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image036.jpg

 

The structure of the meninges, with the superposition of pia mater, arachnoid, and dura mater. Astrocytes form a 3-dimensional net around the neurons (not shown). Note that the footlike processes of the astrocytes form a continuous layer that involves the blood vessels that contribute to the blood-brain barrier.

 

 

Pia Mater

 

The pia mater is a loose connective tissue contain­ing many blood vessels. Although it is located quite close to the nerve tissue, it is not in contact with nerve cells or fibers. Between the pia mater and the neural el­ements is a thin layer of neuroglial processes, adhering firmly to the pia mater and forming a physical barrier at the periphery of the central nervous system. This barrier separates the central nervous system from the cerebrospinal fluid.

The pia mater follows all the irregularities of the surface of the central nervous system and penetrates it to some extent along with the blood vessels. Pia mater is covered by squamous cells of mesenchymal origin.

Blood vessels penetrate the central nervous system through tunnels covered by pia mater – the perivascular spaces. The pia mater disappears before the blood vessels are transformed into capillaries. In the central nervous system, the blood capillaries are completely covered by expansions of the neuroglial cell processes.

 

Blood-Brain Barrier

 

The blood-brain barrier is a functional barrier that prevents the passage of some substances, such as an­tibiotics and chemical and bacterial toxic matter, from the blood to nerve tissue.

 

The blood-brain barrier results from the reduced permeability that is a property of blood capillaries of nerve tissue. Occluding junctions, who provide continuity between the endothelial cells of these cap­illaries, represent the main structural component of the barrier. The cytoplasm of these endothelial cells does not have the fenestrations found in many other locations, and very few pinocytotic vesicles are ob­served. The expansions of neuroglial cell processes that envelop the capillaries are partly responsible for their low permeability.

 

HOROID PLEXUS & CEREBROSPINAL FLUID

 

The choroid plexus consists of invaginated folds of pia mater that penetrate the interior of the ventricles. It is found in the roofs of the third and fourth ventricles and in part in the walls of the lateral ventricles. It is a vascular structure made up of dilated fenestrated capillaries.

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image038.jpg

 

Photomicrograph of choroid plexus section. The choroid plexus presents a core of loose connective tissue rich in blood capillaries (BC) covered by a simple cubic epithelium (arrowhead). H&E stain. Medium magnification.

 

The choroid plexus is composed of loose connective tissue of the pia mater, covered by a simple cuboidal or low columnar epithelium that has the cytologic characteristics of ion-transporting cells.

The main function of the choroid plexus is to elaborate cerebrospinal fluid, which contains only a small amount of solids and completely fills the ventricles, central canal of the spinal cord, subarachnoid space, and perivascular space. Cerebrospinal fluid is important for the metabolism of the central nervous system and acts as a protective device.

Cerebrospinal fluid is very low in protein content. A few desquamated cells and two to five lymphocytes per milliliter are also present. Cerebrospinal fluid circulates through the ventricles, from which it passes into the subarachnoid space. There, arachnoid villi provide the main pathway for absorption of cerebrospinal fluid into the venous circulation. There are no lymphatic vessels ierve tissue.

A decrease in the absorption of cerebrospinal fluid or a blockage of outflow from the ventricles results in the condition known as hydrocephalus (Or. hydro, water, + kephale, head), which promotes a progressive enlargement of the head followed by mental impairment and muscular weakness.

 

Students’ Practical Activities

 

Specimen 1. Cerebral cortex.

Silver impregnation.

 

The cerebral hemispheres consist of a convoluted cortex of grey matter overlying the central medullary mass of white matter which conveys fibers between different parts of the cortex and to and from other parts of the central nervous system. The neurons are arranged into six layers, the layers differing in characteristic neurone morphology, size and population density. The layers merge with one another rather than being highly demarcated and vary somewhat from one region of the cortex to another depending on cortical thickness and function.

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image039.jpg

 

Specimen illustrates the typical layered appearance of the cerebral cortex, the more detailed characteristics of each layer being as follows:

1. Plexiform (molecular) layer. This most superficial layer mainly contains dendrites and axons of cortical neurons making synapses with one another; the sparse nuclei are those of neuroglia and occasional horizontal cells of Cajal.

Horizontal cells of Cajal are small and spindle-shaped but oriented parallel to the surface. They are the least common cell type and are only found in the most superficial layer where their axons pass laterally to synapse with the dendrites of pyramidal cells.

2. Outer granular layer. A dense population of small pyramidal cells and stellate cells make up this thin layer which also contains various axons and dendrites connections from deeper layer.

Stellate (granule) cells are small neurons with a short vertical axon and several short branching dendrites giving the cell body the shape of star. With routine histological methods the cells look like small granules giving rise to their alternative name.

3. Pyramidal cell layer. Pyramidal cells of moderate size predominate in this broad layer, the cells increasing in size deeper in the layer.

Pyramidal cells have pyramid-shape cell bodies, the apex being directed towards the cortical surface. A thin axon arises from the base of the cell and passes into the underlying white matter, though in the case of small superficially located cells, the axon may synapse in the deep layers of the cortex. From the apex, a thick branching dendrite passes towards the surface where it has a prolific array of fine dendrites branches. In addition, short dendrites arise from the edges of the base and ramify laterally. The size oh pyramidal cells varies from small to large, the smallest tending to lie more superficially.

4. Inner granular layer. This narrow layer consists mainly of densely packed stellate cells.

5. Ganglionic layer. Large pyramidal cells and smaller numbers of stellate cells and cells of Martinotti make up this layer, the name of the layer originating from the huge pyramidal (ganglion) Betz cells of the motor cortex.

6. Multiform cell layer. So named on account of the wide variety of differing morphological forms found in this layer, the layer contains numerous small pyramidal cells and cells of Martinotti, as well as stellate cells especially superficially, and fusiform cells in the deeper part.

Cells of Martinotti are small polygonal cells with a few short dendrites and the axon extending toward the surface and bifurcating to run horizontally, most commonly in the most superficial layer.

Fusiform cells are spindle-shaped cells oriented at right angels to the surface. The axon arises from the side of the cell body and passes superficially. Dendrites extend from each end of the cell body branching so as to pass vertically into deeper and more superficial layers.

In addition to neurons, the cortex contains supporting neuroglial cells i.e. astrocytes, oligodendrocytes and microglia.

 

Illustrate and indicate: I. Cerebral cortex: 1. Plexiform (molecular) layer; 2. Outer granular layer; 3.Pyramidal cell layer; 4.Inner granular layer; 5.Ganglionic layer; 6.Multiform cell layer; II.White matter.

 

Specimen 2.Cerebellum.

Stained with H&E.

 

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/en/med/lik/ptn/1/12%20Cerebellum.%20Hemispheres%20of%20the%20brain.%20Autonomic%20nerve%20system_files/image040.jpg

 

Higher magnification of cerebellar cortex, showing the row of large Purkinje cells lying between the outer and inner cortical layers. The stubs of the dendritic trees of the Purkinje cells look rather like “antlers” arising from the cell bodies. Very complex dendritic brunching actually extend throughout the molecular layer above the Purkinje c ells. A single axon leaves each Purkinje cell at its oval base and descends through the granular layer to deeper relay stations within the brain. Again, these are neurons with a very distinctive shape.

As seen in specimen, the cerebellum cortex forms a series of deeply convoluted folds or folia supported by a branching central medulla of white matter. The cortex is seen to consist of three layers, an outer layer containing relatively few cells (the so-called molecular-layer), an extremely cellular inner layer (the so-called granule cell layer) and a single intervening layer of huge neurons called Purkinje cells. The Purkinje cells have huge cell bodies, a relatively fine axon extending down through the granule cell layer, and an extensively branching dendritic system, which arborises into the outer molecular layer.

The deep granule cell layer of the cortex contains numerous small neurons, the non-myelinated axons of which pass outwards to the molecular layer where they bifurcate to run parallel to the surface to synapse with the dendrities of Purkinje cells; each granule cell synapses with several hundred Purkinje cells. There are three other types of small neurons in the cerebellar cortex, namely, stellate cells and basket cells scattered in the outer molecular layer and Golgi cells scattered in the superficial part of the granule cell layer.

 

Illistrate and indicate: I. Cerebellar cortex: 1. Molecular layer; 2. Single layer of huge neurons: a) Purkinje cells. 3. Granule cell layer; II. White matter.

 

References:

a) basic

1.                 Practical classes materials.

2.                 Lectury presentation.

3.                 Stevens A. Human Histology / A. Stevens, J. Lowe. – [second edition]. Mosby, 2000. P. 86-91.

4.                 Wheter’s Functional Histology : A Text and Colour Atlas / [Young B., Lowe J., Stevens A., Heath J.]. Elsevier Limited, 2006. – P. 392-399.

5.                 Ross M. Histology : A Text and Atlas / M. Ross W.Pawlina. – [sixth edition]. – Lippincott Williams and Wilkins, 2011. – P. 394-398.

b) additional

6. Eroschenko V.P. Atlas of Histology with functional correlations / Eroschenko V.P. [tenthedition]. – Lippincott Williams and Wilkins, 2008. – P. 147-153.

7. Charts:

http://intranet.tdmu.edu.ua/index.php?dir_name=kafedra&file_name=tl_34.php#n15

8. Volkov K. S. Ultrastructure of cells and tissues / K. S. Volkov, N. V. Pasechko. – Ternopil :Ukrmedknyha, 1997. – P. 10-20.

http://en.wikipedia.org/wiki/Histology

http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html

http://www.udel.edu/biology/Wags/histopage/histopage.htm

 

 

 

 

 

Leave a Reply

Your email address will not be published. Required fields are marked *

Приєднуйся до нас!
Підписатись на новини:
Наші соц мережі