Global Pallidus
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The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a major component of the
subcortical The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of neural integration in the central nervous system, and plays a key ...
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
in the
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
. It consists of two adjacent segments, one external (or lateral), known in rodents simply as the globus pallidus, and one internal (or medial). It is part of the
telencephalon The cerebrum (: cerebra), telencephalon or endbrain is the largest part of the brain, containing the cerebral cortex (of the two cerebral hemispheres) as well as several subcortical structures, including the hippocampus, basal ganglia, and olf ...
, but retains close functional ties with the
subthalamus The subthalamus or ventral thalamus is a part of the diencephalon. Its most prominent structure is the subthalamic nucleus. The subthalamus connects to the globus pallidus, a subcortical nucleus of the basal ganglia. Structure The subthalamus ...
in the
diencephalon In the human brain, the diencephalon (or interbrain) is a division of the forebrain (embryonic ''prosencephalon''). It is situated between the telencephalon and the midbrain (embryonic ''mesencephalon''). The diencephalon has also been known as t ...
– both of which are part of the extrapyramidal motor system. The globus pallidus receives principal inputs from the
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
, and principal direct outputs to the
thalamus The thalamus (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...
and the
substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...
. The latter is made up of similar neuronal elements, has similar afferents from the striatum, similar projections to the thalamus, and has a similar synaptology. Neither receives direct cortical afferents, and both receive substantial additional inputs from the
intralaminar thalamic nuclei The intralaminar thalamic nuclei (ITN) are collections of neurons in the medullary laminae of thalamus, internal medullary lamina of the thalamus.Mancall, E., Brock, D. & Gray, H. (2011). Gray's clinical neuroanatomy the anatomic basis for clinical ...
. Globus pallidus is
Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...
for "pale globe".


Structure

Pallidal nuclei are made up of the same neuronal components. In primates, almost all pallidal neurons are very large,
parvalbumin Parvalbumin (PV) is a calcium-binding protein with low molecular weight (typically 9–11 kDa). In humans, it is encoded by the ''PVALB'' gene. It is a member of the albumin family; it is named for its size (''parv-'', from Latin ' which means " ...
-positive, with very large dendritic arborizations. These have the peculiarity of having the three-dimensional shape of flat discs, parallel to one another, parallel to the border of the pallidum and perpendicular to the afferent striatopallidal
axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...
s. There are only a few small local circuitry neurons. The globus pallidus is traversed by the numerous
myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...
ated axons of the
striatopallidonigral bundle The basal ganglia form a major brain system in all vertebrates, but in primates (including humans) there are special differentiating features. The basal ganglia include the striatum, globus pallidus, substantia nigra and subthalamic nucleus. In pr ...
that give it the pale appearance from which it is named. The ultrastructure is very peculiar, as the long dendrites are everywhere, without discontinuity, covered by synapses.Fox, C.A., Andrade, A.N. Du Qui, I.J., Rafols, J.A. (1974) The primate globus pallidus. A Golgi and electron microscopic study. J. Hirnforsch. 15: 75–93di Figlia, M., Pasik, P., Pasik, T. (1982) A Golgi and ultrastructural study of the monkey globus pallidus. J. Comp. Neurol. 212: 53–75


Parts

In primates, the globus pallidus is divided into two parts by a thin medial medullary lamina. These are the
internal globus pallidus The internal globus pallidus (GPi or medial globus pallidus) is one of the two subcortical nuclei that provides inhibitory output in the basal ganglia, the other being the substantia nigra pars reticulata. Together with the external globus pallid ...
(GPi) and the
external globus pallidus The external globus pallidus (GPe or lateral globus pallidus) combines with the internal globus pallidus (GPi) to form the globus pallidus, an anatomical subset of the basal ganglia. Globus pallidus means "pale globe" in Latin, indicating its app ...
(GPe); both are composed of closed nuclei surrounded by myelinic walls. The
ventral pallidum The ventral pallidum (VP) is a structure within the basal ganglia of the brain. It is an output nucleus whose fibres project to thalamic nuclei, such as the ventral anterior nucleus, the ventral lateral nucleus, and the medial dorsal nucleus ...
lies within the
substantia innominata The substantia innominata, also innominate substance or substantia innominata of Meynert (Latin for unnamed substance), is a series of layers in the human brain consisting partly of gray and partly of white matter, which lies below the anterior par ...
(Latin for unnamed substance) and receives efferent connections from the ventral
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
(the
nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...
and the
olfactory tubercle The olfactory tubercle (OT), also known as the tuberculum olfactorium, is a multi-sensory processing center that is contained within the olfactory cortex and ventral striatum and plays a role in reward cognition. The OT has also been shown to ...
). It projects to the dorsomedial nucleus of the dorsal
thalamus The thalamus (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...
, which, in turn, projects to the
prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...
; it also projects to the
pedunculopontine nucleus The pedunculopontine nucleus (PPN) or pedunculopontine tegmental nucleus (PPT or PPTg) is a collection of neurons located in the upper pons in the brainstem. It is involved in voluntary movements, arousal, and provides sensory feedback to the cere ...
and tegmental motor areas. Its function is to serve as a limbic-somatic motor interface, and it is involved in the planning and inhibition of movements from the dorsal striatopallidal complex.


Function

The globus pallidus is a structure in the brain involved in the regulation of voluntary movement. It is part of the
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
, which, among many other functions, regulate movements that occur on the subconscious level. The globus pallidus has a predominantly inhibitory effect on movement regulation, balancing cerebellar excitation. Pulsatile and regular interaction between these complementary systems allows smooth and controlled movement. Imbalances can result tremors, jerks,
dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...
,
chorea Chorea, or (rarely) choreia, () is an abnormal involuntary movement disorder, characterized by quick movements of the hands or feet. It is one of a group of neurological disorders called dyskinesias. The term ''chorea'' is derived , as the move ...
and progressive motor weakness ending in diaphragmatic dysfunction, with the most common cause of mortality in most neurodegenerative disorders being
aspiration pneumonia Aspiration pneumonia is a type of lung infection that is due to a relatively large amount of material from the stomach or mouth entering the lungs. Signs and symptoms often include fever and cough of relatively rapid onset. Complications may incl ...
. The basal ganglia acts on a subconscious level, requiring no conscious effort to function. When someone makes a decision to engage in an activity such as petting a dog, for example, these structures help to regulate the movement to make it as smooth as possible, and to respond to sensory feedback. Likewise, the globus pallidus is involved in the constant subtle regulation of movement that allows people to walk and engage in a wide variety of other activities with a minimal level of disruption.


Pallidonigral pacemaker

The two pallidal nuclei and the two parts of the substantia nigra (the
pars compacta The pars compacta (SNpc, SNc) is one of two subdivisions of the ''substantia nigra'' of the midbrain (the other being the pars reticulata); it is situated medial to the ''pars reticulata''. It is formed by dopaminergic neurons. It projects to th ...
and
pars reticulata The pars reticulata (SNpr) is a portion of the substantia nigra and is located lateral to the pars compacta. Most of the neurons that project out of the pars reticulata are inhibitory GABAergic neurons (i.e., these neurons release GABA, which is ...
) constitute a high-frequency autonomous pacemaker. (see primate basal ganglia#Pallidonigral set and pacemaker)


Common afferents

The two parts receive successively a large quantity of
GABAergic In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter gamma-aminobutyric acid (GABA). For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic ...
axonal terminal arborisations from the
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
through the dense striato-pallidonigral bundle. The synaptology is very peculiar (see primate basal ganglia system). The striatal afferents contribute more than 90% of synapses. The two pallidal nuclei receive dopaminergic axons from the pars compacta of the substantia nigra.


Pathway

This area of the basal ganglia receives input from another area, called the striatum, which has two parts, the
caudate nucleus The caudate nucleus is one of the structures that make up the corpus striatum, which is part of the basal ganglia in the human brain. Although the caudate nucleus has long been associated with motor processes because of its relation to Parkinso ...
and the
putamen The putamen (; from Latin, meaning "nutshell") is a subcortical nucleus (neuroanatomy), nucleus with a rounded structure, in the basal ganglia nuclear group. It is located at the base of the forebrain and above the midbrain. The putamen and c ...
. This data is routed to the thalamus, either directly or indirectly. In the case of the interna, one area of the globus pallidus, the structure can feed directly to the thalamus. The externa, which lies on the outside of this structure, feeds information to the interna, where it can be passed on to the thalamus.


Disease

Infarction Infarction is tissue death (necrosis) due to Ischemia, inadequate blood supply to the affected area. It may be caused by Thrombosis, artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as a ...
of the globus pallidus can be seen with
anoxic brain injury Cerebral hypoxia is a form of hypoxia (reduced supply of oxygen), specifically involving the brain; when the brain is completely deprived of oxygen, it is called ''cerebral anoxia''. There are four categories of cerebral hypoxia; they are, in o ...
,
carbon monoxide Carbon monoxide (chemical formula CO) is a poisonous, flammable gas that is colorless, odorless, tasteless, and slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the si ...
poisoning and drug overdoses (
MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly known as ecstasy (tablet form), and molly (crystal form), is an empathogen–entactogenic drug with stimulant and minor Psychedelic drug, psychedelic properties. In studies, it has been used ...
and
heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...
), with the insult classically being
bilateral Bilateral may refer to any concept including two sides, in particular: *Bilateria, bilateral animals *Bilateralism, the political and cultural relations between two states *Bilateral, occurring on both sides of an organism ( Anatomical terms of l ...
. Bilateral calcification can occur in a lentiform shape with aggressive
parenteral nutrition Parenteral nutrition (PN), or intravenous feeding, is the feeding of nutritional products to a person intravenously, bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding entities or standard ph ...
. Encephalopathy, as can occur with
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
or
Leigh syndrome Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who fir ...
, also causes globus pallidus abnormalities, making them bright on
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
T1 sequences in liver disease and on bright on T2 sequences with Leigh syndrome. Additional substances that can accumulate in the basal ganglia include heavy metals (such as
gadolinium Gadolinium is a chemical element; it has Symbol (chemistry), symbol Gd and atomic number 64. It is a silvery-white metal when oxidation is removed. Gadolinium is a malleable and ductile rare-earth element. It reacts with atmospheric oxygen or moi ...
, iron and
copper Copper is a chemical element; it has symbol Cu (from Latin ) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish-orang ...
),
calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...
and
amyloid Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human ...
with
hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...
. Clumps of disorganized nerve tissue, can accumulate inside the globus pallidus with
neurofibromatosis type I Neurofibromatosis type I (NF-1), or von Recklinghausen syndrome, is a complex multi-system neurocutaneous disorder caused by a subset of genetic mutations at the neurofibromin 1 (''NF1'') locus. Other conditions associated with mutation of the ...
, causing severe neurologic dysfunction. The pallidus can also be destroyed by rare metabolic disorders such as PKAN,
methylmalonic acidemias Methylmalonic acidemias, also called methylmalonic acidurias, are a group of inherited metabolic disorders, that prevent the body from properly breaking down proteins and fats. This leads to a buildup of a toxic level of methylmalonic acid in body ...
and
maple syrup urine disease Maple syrup urine disease (MSUD) is a rare, inherited metabolic disorder that affects the body's ability to metabolize amino acids due to a deficiency in the activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex. It parti ...
. Though damage to the globus pallidus can cause
movement disorders Movement disorders are clinical syndromes with either an excess of movement or a paucity of voluntary and involuntary movements, unrelated to weakness or spasticity. Movement disorders present with extrapyramidal symptoms and are caused by basal ...
, diseases like
Parkinson's Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become more prevalen ...
and
essential tremor Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations ( oscillations or twitching movements) of certain muscle groups i ...
can paradoxically be treated by surgically inducing lesions in the nuclei using ultrasound,
Gamma knife Radiosurgery is surgery using radiation, that is, the destruction of precisely selected areas of tissue (biology), tissue using ionizing radiation rather than excision with a blade. Like other forms of radiation therapy (also called radiotherapy), ...
, or more rarely open surgery. The nucleus can also be artificially stimulated using
deep brain stimulation Deep brain stimulation (DBS) is a type of neurostimulation therapy in which an implantable pulse generator is stereotactic surgery, surgically implanted subcutaneous tissue, below the skin of the chest and connected by Lead (electronics), leads ...
in which a battery pack is inserted into the chest wall and electrical leads run up the neck and into the brain from the back of the skull. The aim of these procedures is to reduce involuntary muscle tremors and improve extrapyramidal symptoms associated with neurodegeneration, though they can impact intellectual function and cause
dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. It is a condition in which problems effectively occur with the ...
.McCartney, L. K., Bau K., Stewart K., Botha B., Morrow A., (2016), Pallidotomy as a treatment option for a complex patient with severe dystonia, Dev. Med. Child Neurol. 2016 58: (68–69) http://onlinelibrary.wiley.com/doi/10.1111/dmcn.13070/epdf


History

The origin of the name is not established. It was used by Joseph Dejerine (1906) but not by
Santiago Ramón y Cajal Santiago Ramón y Cajal (; 1 May 1852 – 17 October 1934) was a Spanish neuroscientist, pathologist, and histologist specializing in neuroanatomy, and the central nervous system. He and Camillo Golgi received the Nobel Prize in Physiology or M ...
(1909–1911). As the elements in no way have the shape of a globe, throughout the 20th century scientists proposed a simpler term (a neuter adjective), ''pallidum'' (meaning "pale"). Propositions include those by Foix and Nicolesco (1925), the Vogts (1941), Crosby et al. (1962) and the ''
Terminologia Anatomica ''Terminologia Anatomica'' (commonly abbreviated TA) is the international standard for human anatomy, human anatomical terminology. It is developed by the Federative International Programme on Anatomical Terminology (FIPAT) a program of the Inter ...
''. For a long time the globus pallidus was linked to the putamen and termed the
lentiform nucleus The lentiform nucleus (or lentiform complex, lenticular nucleus, or lenticular complex) are the putamen (laterally) and the globus pallidus (medially), collectively. Due to their proximity, these two structures were formerly considered one, howev ...
(nucleus lenticularis or lentiformis), a heterogeneous anatomical entity that is part of the
striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
rather than the pallidum. The link with the
substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...
pars reticulata was stressed very early on due to the similarities in dendritic arborisation (and they are sometimes known as the pallidonigral set) but, in spite of strong evidence, this association remains controversial.


Animal Studies

In rodents, the globus pallidus internus is also known as the entopeduncular nucleus.


See also

*
Lentiform nucleus The lentiform nucleus (or lentiform complex, lenticular nucleus, or lenticular complex) are the putamen (laterally) and the globus pallidus (medially), collectively. Due to their proximity, these two structures were formerly considered one, howev ...


References


External links

*
Diagram at uni-tuebingen.de
{{DEFAULTSORT:Globus Pallidus Basal ganglia