Decussation is used in biological contexts to describe a crossing. The anatomical term chiasma is named after the Greek uppercase'Χ', chi). Examples include: In the brain, where nerve fibers obliquely cross from one lateral part to the other, to say they cross at a level other than their origin. See for examples Decussation of pyramids and sensory decussation. Decussation describes the point where the nerves cross from one side of the brain to the other, the nerves from the left side of the body decussate to the right side of the brain and the nerves from the right side of the body decussate to the left brain, however depending on the function of the nerves the level of decussation is variable. In neuroanatomy the term chiasma is reserved for the crossing of nerves outside the brain, such as the optic chiasm. In botanical leaf taxology, the word decussate describes an opposite pattern of leaves which has successive pairs at right angles to each other. In effect, successive pairs of leaves cross each other.
Basil is a classic example of a decussate leaf pattern. In tooth enamel, where bundles of rods cross each other as they travel from the enamel-dentine junction to the outer enamel surface, or near to it. In taxonomic description where decussate markings or structures occur, names such as decussatus or decussata or otherwise in part containing "decuss..." are common in the specific epithet. The origin of the contralateral organization, the optic chiasm and the major decussations on the nervous system of vertebrates has been a long standing puzzle to scientists. For long the visual map theory of Ramón y Cajal has been the most popular theory. More scientists have realized that this theory has some severe flaws. According to the current theory, the decussations are caused by an axial twist which makes it so that the anterior head, along with the forebrain, is turned by 180° with respect to the rest of the body. Commissure Why does the nervous system decussate?: Stanford Neuroblog Media related to Decussation at Wikimedia Commons
Astrocytes known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. The proportion of astrocytes in the brain is not well defined. Depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to 40% of all glia, they perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, a role in the repair and scarring process of the brain and spinal cord following traumatic injuries. Research since the mid-1990s has shown that astrocytes propagate intercellular Ca2+ waves over long distances in response to stimulation, similar to neurons, release transmitters in a Ca2+-dependent manner. Data suggest that astrocytes signal to neurons through Ca2+-dependent release of glutamate; such discoveries have made astrocytes an important area of research within the field of neuroscience.
Astrocytes are a sub-type of glial cells in the central nervous system. They are known as astrocytic glial cells. Star-shaped, their many processes envelop synapses made by neurons. Astrocytes are classically identified using histological analysis. Several forms of astrocytes exist in the central nervous system including fibrous and radial; the fibrous glia are located within white matter, have few organelles, exhibit long unbranched cellular processes. This type has "vascular feet" that physically connect the cells to the outside of capillary walls when they are in proximity to them; the protoplasmic glia are the most prevalent and are found in grey matter tissue, possess a larger quantity of organelles, exhibit short and branched tertiary processes. The radial glial cells are disposed in planes perpendicular to the axes of ventricles. One of their processes abuts the pia mater, while the other is buried in gray matter. Radial glia are present during development, playing a role in neuron migration.
Müller cells of the retina and Bergmann glia cells of the cerebellar cortex represent an exception, being present still during adulthood. When in proximity to the pia mater, all three forms of astrocytes send out processes to form the pia-glial membrane. Astrocytes are macroglial cells in the central nervous system. Astrocytes are derived from heterogeneous populations of progenitor cells in the neuroepithelium of the developing central nervous system. There is remarkable similarity between the well known genetic mechanisms that specify the lineage of diverse neuron subtypes and that of macroglial cells. Just as with neuronal cell specification, canonical signaling factors like Sonic hedgehog, Fibroblast growth factor, WNTs and bone morphogenetic proteins, provide positional information to developing macroglial cells through morphogen gradients along the dorsal–ventral, anterior–posterior and medial–lateral axes; the resultant patterning along the neuraxis leads to segmentation of the neuroepithelium into progenitor domains for distinct neuron types in the developing spinal cord.
On the basis of several studies it is now believed that this model applies to macroglial cell specification. Studies carried out by Hochstim and colleagues have demonstrated that three distinct populations of astrocytes arise from the p1, p2 and p3 domains; these subtypes of astrocytes can be identified on the basis of their expression of different transcription factors and cell surface markers. The three populations of astrocyte subtypes which have been identified are 1) dorsally located VA1 astrocytes, derived from p1 domain, express PAX6 and reelin 2) ventrally located VA3 astrocytes, derived from p3, express NKX6.1 and SLIT1 and 3) and intermediate white-matter located VA2 astrocyte, derived from the p2 domain, which express PAX6, NKX6.1, reelin and SLIT1. After astrocyte specification has occurred in the developing CNS, it is believed that astrocyte precursors migrate to their final positions within the nervous system before the process of terminal differentiation occurs. In medical science, the neuronal network was considered the only important function of astrocytes, they were looked upon as gap fillers.
More the function of astrocytes has been reconsidered, they are now thought to play a number of active roles in the brain, including the secretion or absorption of neural transmitters and maintenance of the blood–brain barrier. Following on this idea the concept of a tripartite synapse has been proposed, referring to the tight relationship occurring at synapses among a presynaptic element, a postsynaptic element and a glial element. Structural: They are involved in the physical structuring of the brain. Astrocytes get their name because they are "star-shaped", they are the most abundant glial cells in the brain that are associated with neuronal synapses. They regulate the transmission of electrical impulses within the brain. Glycogen fuel reserve buffer: Astrocytes contain glycogen and are capable of gluconeogenesis; the astrocytes next to neurons in hippocampus store and release glucose. Thus, astrocytes can fuel neurons with glucose during periods of high rate of glucose consumption and glucose shortage.
A recent research on rats suggests there may be a connection between this activity and physical exercise. Metabolic support: They provide neurons with nutrients such as lactate. Glucose sensing: associated w
The commissural fibers or transverse fibers are axons that connect the two hemispheres of the brain. In contrast to commissural fibers, association fibers connect regions within the same hemisphere of the brain, projection fibers connect each region to other parts of the brain or to the spinal cord; the commissural fibers make up tracts that include the corpus callosum, the anterior commissure, the posterior commissure. The corpus callosum is the largest commissural tract in the human brain, it consists of about 200-300 million axons. The corpus callosum is essential to the communication between the two hemispheres. A recent study of individuals with agenesis of the corpus callosum suggests that the corpus callosum plays a vital role in problem solving strategies, verbal processing speed, executive performance; the absence of a developed corpus callosum is shown to have a significant relationship with impaired verbal processing speed and problem solving. Another study of individuals with multiple sclerosis provides evidence that structural and microstructural abnormalities of the corpus callosum are related to cognitive dysfunction.
Verbal and visual memory, information processing speed, executive tasks were shown to be impaired when compared to healthy individuals. Physical disabilities in multiple sclerosis patients seem to be related to abnormalities of the corpus callosum, but not to the same extent of other cognitive functions. Using diffusion tensor imaging, researchers have been able to produce a visualization of this network of fibers, which shows the corpus callosum has an anteroposterior topographical organization, uniform with the cerebral cortex; the anterior commissure is a tract that connects the two temporal lobes of the cerebral hemispheres across the midline, placed in front of the columns of the fornix. The great majority of fibers connecting the two hemispheres travel through the corpus callosum, over 10 times larger than the anterior commissure, other routes of communication pass through the hippocampal commissure or, via subcortical connections; the anterior commissure is a significant pathway that can be distinguished in the brains of all mammals.
Using diffusion tensor imaging, researchers were able to approximate the location of the anterior commissure where it crosses the midline of the brain. This tract can be observed to be in the shape of a bicycle as it branches through various areas of the brain. Through diffusion tensor imaging results, the anterior commissure was categorized into two fiber systems: 1) the olfactory fibers and 2) the non-olfactory fibers; the posterior commissure is a rounded nerve tract crossing the middle line on the dorsal aspect of the upper end of the cerebral aqueduct. It is important in the bilateral pupillary light reflex. Evidence suggests the posterior commissure is a tract that plays a role in language processing between the right and left hemispheres of the brain, it connects the pretectal nuclei. A case study described in The Irish Medical Journal discussed the role the posterior commissure plays in the connection between the right occipital cortex and the language centers in the left hemisphere; this study explains how visual information from the left side of the visual field is received by the right visual cortex and transferred to the word form system in the left hemisphere though the posterior commissure and the splenium.
Disruption of the posterior commissure can cause alexia without agraphia. It is evident from this case study of alexia without agraphia that the posterior commissure plays a vital role in transferring information from the right occipital cortex to the language centers of the left hemisphere; the lyra or hippocampal commissure. Aging Age-related decline in the commissural fiber tracts that make up the corpus callosum indicate the corpus callosum is involved in memory and executive function; the posterior fibers of the corpus callosum are associated with episodic memory. Perceptual processing decline is related to diminished integrity of occipital fibers of the corpus callosum. Evidence suggests that the genu of the corpus callosum does not contribute to any one cognitive domain in the elderly; as fiber tract connectivity in the corpus callosum declines due to aging, compensatory mechanisms are found in other areas of the corpus callosum and frontal lobe. These compensatory mechanisms, increasing connectivity in other parts of the brain, may explain why elderly individuals still display executive function as a decline of connectivity is seen in regions of the corpus callosum.
Older adults compared to younger adults show poorer performance in balance tests. A decline in white matter integrity of the corpus callosum in older individuals may explain declines in the ability to balance. Changes in the white matter integrity of the corpus callosum may be related to cognitive and motor function decline as well. Decreased white matter integrity effects proper transmission and processing of sensorimotor information. White matter degeneration of the genu of the corpus callosum is associated with gait, balance impairment, the quality of postural control; the corpus callosum allows for communication between the two hemispheres and is found only in placental mammals, while it is absent in monotremes and marsupials, as well as other vertebrates such as birds, reptiles and fish. The anterior commissure serves as the primary mode of interhemispheric communication in marsupials, which carries all the commissural fibers arising from the neocortex, whereas in pl
Myelin is a lipid-rich substance formed in the central nervous system by glial cells called oligodendrocytes, in the peripheral nervous system by Schwann cells. Myelin insulates nerve cell axons to increase the speed at which information travels from one nerve cell body to another or, for example, from a nerve cell body to a muscle; the myelinated axon can be likened to an electrical wire with insulating material around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, each myelin sheath insulates the axon over a single section and, in general, each axon comprises multiple long myelinated sections separated from each other by short gaps called Nodes of Ranvier; each myelin sheath is formed by the concentric wrapping of an oligodendrocyte or Schwann cell process around the axon. More myelin speeds the transmission of electrical impulses called action potentials along myelinated axons by insulating the axon and reducing axonal membrane capacitance.
This results in saltatory conduction whereby the action potential "jumps" from one node of Ranvier, over a long myelinated stretch of the axon called the internode, before "recharging" at the next node of Ranvier, so on, until it reaches the axon terminal. Nodes of Ranvier are the short unmyelinated regions of the axon between adjacent long myelinated internodes. Once it reaches the axon terminal, this electrical signal provokes the release of a chemical message or neurotransmitter that binds to receptors on the adjacent post-synaptic cell at specialised regions called synapses; this "insulating" role for myelin is essential for normal motor function, sensory function and cognition, as demonstrated by the consequences of disorders that affect it, such as the genetically determined leukodystrophies. Due to its high prevalence, multiple sclerosis, which affects the central nervous system, is the best known disorder of myelin; the process of generating myelin is called myelination or myelinogenesis.
In the CNS, cells called oligodendrocyte precursor cells differentiate into mature oligodendrocytes, which form myelin. In humans, myelination begins early in the 3rd trimester, although only little myelin is present in either the CNS or the PNS at the time of birth. During infancy, myelination progresses with increasing numbers of axons acquiring myelin sheaths; this corresponds with the development of cognitive and motor skills, including language comprehension, speech acquisition and walking. Myelination continues through adolescence and early adulthood and although complete at this time, myelin sheaths can be added in grey matter regions such as the cerebral cortex, throughout life. Myelin is considered a defining characteristic of the jawed vertebrates, but axons are ensheathed by glial cells in invertebrates, although these glial-wraps are quite different from vertebrate compact myelin, formed, as indicated above, by concentric wrapping of the myelinating cell process multiple times around the axon.
Myelin was first described in 1854 by Rudolf Virchow, although it was over a century following the development of electron microscopy, that its glial cell origin and its ultrastructure became apparent. In vertebrates, not all axons are myelinated. For example, in the PNS, a large proportion of axons are unmyelinated. Instead, they are ensheathed by non-myelinating Schwann cells known as Remak SCs and arranged in Remak bundles. In the CNS, non-myelinated, intermingle with myelinated ones and are entwined, at least by the processes of another type of glial cell called the astrocyte. CNS myelin differs in composition and configuration from PNS myelin, but both perform the same "insulating" function. Being rich in lipid, myelin appears white. Both CNS white matter tracts and PNS nerves each comprise thousands to millions of axons aligned in parallel. Blood vessels provide the route for oxygen and energy substrates such as glucose to reach these fibre tracts, which contain other cell types including astrocytes and microglia in the CNS and macrophages in the PNS.
In terms of total mass, myelin comprises 40% water. Protein content includes myelin basic protein, abundant in the CNS where it plays a critical, non-redundant role in formation of compact myelin. In the PNS, myelin protein zero has a similar role to that of PLP in the CNS in that it is involved in holding together the multiple concentric layers of glial cell membrane that constitute the myelin sheath; the primary lipid of myelin is a glycolipid called galactocerebroside. The intertwining hydrocarbon chains of sphingomyelin strengthen the
The blood vessels are a part of the circulatory system, microcirculation, that transports blood throughout the human body. These vessels are designed to transport nutrients and oxygen to the tissues of the body, they take waste and carbon dioxide and carry them away from the tissues and back to the heart. Blood vessels are needed to sustain life. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the word vascular, meaning relating to the blood vessels, is derived from the Latin vas, meaning vessel. Some structures -- such as cartilage, the epithelium, the lens and cornea of the eye -- do not contain blood vessels and are labeled avascular; the arteries and veins have three layers. The middle layer is thicker in the arteries than it is in the veins: The inner layer, tunica intima, is the thinnest layer, it is a single layer of flat cells glued by a polysaccharide intercellular matrix, surrounded by a thin layer of subendothelial connective tissue interlaced with a number of circularly arranged elastic bands called the internal elastic lamina.
A thin membrane of elastic fibers in the tunica intima run parallel to the vessel. The middle layer tunica media is the thickest layer in arteries, it consists of circularly arranged elastic fiber, connective tissue, polysaccharide substances, the second and third layer are separated by another thick elastic band called external elastic lamina. The tunica media may be rich in vascular smooth muscle. Veins don't have the external elastic lamina, but only an internal one; the tunica media is thicker in the arteries rather than the veins. The outer layer is the thickest layer in veins, it is made of connective tissue. It contains nerves that supply the vessel as well as nutrient capillaries in the larger blood vessels. Capillaries consist of little more than a layer of endothelium and occasional connective tissue; when blood vessels connect to form a region of diffuse vascular supply it is called an anastomosis. Anastomoses provide critical alternative routes for blood to flow in case of blockages. There is a layer of muscle surrounding the arteries and the veins which help contract and expand the vessels.
This creates enough pressure for blood to be pumped around the body. Blood vessels are part of the circulatory system, together with the blood; the biggest difference in the structure of arteries and veins is the presence of valves. Backflow of blood is prevented in arteries by the heart; however in veins, one-direction valves are used to prevent backflow as a result of a decrease in blood pressure as the blood passes through the circulatory system. There are various kinds of blood vessels: Arteries Elastic arteries Distributing arteries Arterioles Capillaries Venules Veins Large collecting vessels, such as the subclavian vein, the jugular vein, the renal vein and the iliac vein. Venae cavae. Sinusoids Extremely small vessels located within bone marrow, the spleen, the liver, they are grouped as "arterial" and "venous", determined by whether the blood in it is flowing away from or toward the heart. The term "arterial blood" is used to indicate blood high in oxygen, although the pulmonary artery carries "venous blood" and blood flowing in the pulmonary vein is rich in oxygen.
This is because they are carrying the blood to and from the lungs to be oxygenated. Blood vessels function to transport blood. In general and arterioles transport oxygenated blood from the lungs to the body and its organs, veins and venules transport deoxygenated blood from the body to the lungs. Blood vessels circulate blood throughout the circulatory system Oxygen is the most critical nutrient carried by the blood. In all arteries apart from the pulmonary artery, hemoglobin is saturated with oxygen. In all veins apart from the pulmonary vein, the saturation of hemoglobin is about 75%. In addition to carrying oxygen, blood carries hormones, waste products and nutrients for cells of the body. Blood vessels do not engage in the transport of blood. Blood is propelled through arterioles through pressure generated by the heartbeat. Blood vessels transport red blood cells which contain the oxygen necessary for daily activities; the amount of red blood cells present in your vessels has an effect on your health.
Hematocrit tests can be performed to calculate the proportion of red blood cells in your blood. Higher proportions result in conditions such as dehydration or heart disease while lower proportions could lead to anemia and long-term blood loss. Blood vessels transport red blood cells which contain the oxygen necessary for daily activities; the amount of red blood cells present in your vessels has an effect on your health. Hematocrit tests can be performed to calculate the proportion of red blood cells in your blood. Higher proportions result in conditions such as dehydration or heart disease while lower proportions could lead to anemia and long-term blood loss. Permeability of the endothelium is pivotal in the release of nutrients to the tissue, it is increased in inflammation in response to histamine and interleukins, which leads to most of the
Microglia are a type of neuroglia located throughout the brain and spinal cord. Microglia account for 10–15% of all cells found within the brain; as the resident macrophage cells, they act as the first and main form of active immune defense in the central nervous system. Microglia are distributed in large non-overlapping regions throughout the CNS. Microglia are key cells in overall brain maintenance—they are scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, infectious agents. Since these processes must be efficient to prevent fatal damage, microglia are sensitive to small pathological changes in the CNS; this sensitivity is achieved in part by the presence of unique potassium channels that respond to small changes in extracellular potassium. The brain and spinal cord, which make up the CNS, are not accessed directly by pathogenic factors in the body's circulation due to a series of endothelial cells known as the blood–brain barrier, or BBB; the BBB prevents most infections from reaching the vulnerable nervous tissue.
In the case where infectious agents are directly introduced to the brain or cross the blood–brain barrier, microglial cells must react to decrease inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the lack of antibodies from the rest of the body, microglia must be able to recognize foreign bodies, swallow them, act as antigen-presenting cells activating T-cells. Microglial cells are plastic, undergo a variety of structural changes based on location and system needs; this level of plasticity is required to fulfill the vast variety of functions that microglia perform. The ability to transform distinguishes microglia from macrophages, which must be replaced on a regular basis, provides them the ability to defend the CNS on short notice without causing immunological disturbance. Microglia adopt a specific form, or phenotype, in response to the local conditions and chemical signals they have detected; the microglial sensome is a new biological concept that appears to be playing a large role in neurodevelopment and neurodegeneration.
The sensome refers to the unique grouping of protein transcripts used for sensing ligands and microbes. In other words, the sensome represents the genes required for the proteins used to sense molecules within the body; the sensome can be analyzed with a variety of methods including qPCR, RNA-seq, microarray analysis, direct RNA sequencing. Genes included in the sensome code for receptors and transmembrane proteins on the plasma membrane that are more expressed in microglia compared to neurons, it does not include secreted proteins or transmembrane proteins specific to membrane bound organelles, such as the nucleus and endoplasmic reticulum. The plurality of identified sensome genes code for pattern recognition receptors, there are a large variety of included genes. Microglial share a similar sensome to other macrophages, however they contain 22 unique genes, 16 of which are used for interaction with endogenous ligands; these differences create a unique microglial biomarker that includes over 40 genes including P2ry12 and HEXB.
DAP12 appears to play an important role in sensome protein interaction, acting as a signalling adaptor and a regulatory protein. The regulation of genes within the sensome must be able to change in order to respond to potential harm. Microglia can take on the role of neurotoxicity in order to face these dangers. For these reasons, it is suspected. Sensome genes that are upregulated with aging are involved in sensing infectious microbial ligands while those that are downregulated are involved in sensing endogenous ligands; this analysis suggests a glial-specific regulation favoring neuroprotection in natural neurodegeneration. This is in contrast to the shift towards neurotoxicity seen in neurodegenerative diseases; the sensome can play a role in neurodevelopment. Early-life brain infection results in microglia that are hypersensitive to immune stimuli; when exposed to infection, there is an upregulation of sensome genes involved in neuroinflammation and a downregulation of genes that are involved with neuroplasticity.
The sensome’s ability to alter neurodevelopment may however be able to combat disease. The deletion of CX3CL1, a expressed sensome gene, in rodent models of Rett syndrome resulted in improved health and longer lifespan; the downregulation of Cx3cr1 in humans without Rett syndrome is associated with symptoms similar to schizophrenia. This suggests that the sensome not only plays a role in various developmental disorders, but requires tight regulation in order to maintain a disease-free state; this form of microglial cell is found at specific locations throughout the entire brain and spinal cord in the absence of foreign material or dying cells. This "resting" form of microglia is composed of a small cellular body. Unlike the amoeboid forms of microglia, the cell body of the ramified form remains in place while its branches are moving and surveying the surrounding area; the branches are sensitive to small changes in physiological condition and require specific culture conditions to observe in vitro.
Unlike activated or ameboid microglia, ramified microglia do not phagocytose cells and secrete fewer immunomolecules. Microglia in this state are able to search for and identify immune threats while maintaining homeostasis in the CNS. Although this is considered the res
Purkinje cells, or Purkinje neurons, are a class of GABAergic neurons located in the cerebellum. They are named after their discoverer, Czech anatomist Jan Evangelista Purkyně, who characterized the cells in 1839; these cells are some of the largest neurons in the human brain, with an intricately elaborate dendritic arbor, characterized by a large number of dendritic spines. Purkinje cells are found within the Purkinje layer in the cerebellum. Purkinje cells are aligned like dominos stacked one in front of the other, their large dendritic arbors form nearly two-dimensional layers through which parallel fibers from the deeper-layers pass. These parallel fibers make weaker excitatory synapses to spines in the Purkinje cell dendrite, whereas climbing fibers originating from the inferior olivary nucleus in the medulla provide powerful excitatory input to the proximal dendrites and cell soma. Parallel fibers pass orthogonally through the Purkinje neuron's dendritic arbor, with up to 200,000 parallel fibers forming a Granule-cell-Purkinje-cell synapse with a single Purkinje cell.
Each Purkinje cell receives 500 climbing fiber synapses, all originating from a single climbing fiber. Both basket and stellate cells provide inhibitory input to the Purkinje cell, with basket cells synapsing on the Purkinje cell axon initial segment and stellate cells onto the dendrites. Purkinje cells send inhibitory projections to the deep cerebellar nuclei, constitute the sole output of all motor coordination in the cerebellar cortex; the Purkinje layer of the cerebellum, which contains the cell bodies of the Purkinje cells and Bergmann glia, express a large number of unique genes. Purkinje-specific gene markers were proposed by comparing the transcriptome of Purkinje-deficient mice with that of wild-type mice. One illustrative example is the Purkinje cell protein 4 in knockout mice, which exhibit impaired locomotor learning and markedly altered synaptic plasticity in Purkinje neurons. PCP4 accelerates both the association and dissociation of calcium with calmodulin in the cytoplasm of Purkinje cells, its absence impairs the physiology of these neurons.
There is evidence in mice and humans that bone marrow cells either fuse with or generate cerebellar Purkinje cells, it is possible that bone marrow cells, either by direct generation or by cell fusion, could play a role in repair of central nervous system damage. Further evidence points yet towards the possibility of a common stem cell ancestor among Purkinje neurons, B-lymphocytes and aldosterone-producing cells of the human adrenal cortex. Purkinje cells show two distinct forms of electrophysiological activity: Simple spikes occur at rates of 17 – 150 Hz, either spontaneously or when Purkinje cells are activated synaptically by the parallel fibers, the axons of the granule cells. Complex spikes are slow, 1–3 Hz spikes, characterized by an initial prolonged large-amplitude spike, followed by a high-frequency burst of smaller-amplitude action potentials, they are caused by climbing fiber activation and can involve the generation of calcium-mediated action potentials in the dendrites. Following complex spike activity, simple spikes can be suppressed by the powerful complex spike input.
Purkinje cells show spontaneous electrophysiological activity in the form of trains of spikes both sodium-dependent and calcium-dependent. This was shown by Rodolfo Llinas. P-type calcium channels were named after Purkinje cells, where they were encountered, which are crucial in cerebellar function. We now know that activation of the Purkinje cell by climbing fibers can shift its activity from a quiet state to a spontaneously active state and vice versa, serving as a kind of toggle switch; these findings have been challenged by a study suggesting that such toggling by climbing-fiber inputs occurs predominantly in anaesthetized animals and that Purkinje cells in awake behaving animals, in general, operate continuously in the upstate. But this latter study has itself been challenged and Purkinje cell toggling has since been observed in awake cats. A computational model of the Purkinje cell has shown intracellular calcium computations to be responsible for toggling. Findings have suggested that Purkinje cell dendrites release endocannabinoids that can transiently downregulate both excitatory and inhibitory synapses.
The intrinsic activity mode of Purkinje cells is controlled by the sodium-potassium pump. This suggests that the pump might not be a homeostatic, "housekeeping" molecule for ionic gradients. Instead, it could be a computation element in the brain. Indeed, a mutation in the Na + - K + pump. Furthermore, using the poison ouabain to block Na+-K+ pumps in the cerebellum of a live mouse induces ataxia and dystonia. Numerical modeling of experimental data suggests that, in vivo, the Na+-K+ pump produces long quiescent punctuations to Purkinje neuron firing. Alcohol inhibits Na+-K+ pumps in the cerebellum and this is how it corrupts cerebellar computation and body co-ordination. In humans, Purkinje cells can be harmed by a variety causes: toxic exposure, e.g. to alcohol or lithium. Gluten ataxia is an autoimmune disease triggere