Basal ganglia labeled at top right.
Basal ganglia on frontal section of brain
|NeuroLex ID||Basal ganglia|
|Anatomical terms of neuroanatomy|
The basal ganglia (or basal nuclei) consist of multiple subcortical nuclei, of varied origin, in the brains of vertebrates, which are situated at the base of the forebrain. Basal ganglia nuclei are strongly interconnected with the cerebral cortex, thalamus, and brainstem, as well as several other brain areas. The basal ganglia are associated with a variety of functions including: control of voluntary motor movements, procedural learning, routine behaviors or "habits" such as bruxism, eye movements, cognition and emotion.
The main components of the basal ganglia – as defined functionally – are the dorsal striatum (caudate nucleus and putamen), ventral striatum (nucleus accumbens and olfactory tubercle), globus pallidus, ventral pallidum, substantia nigra, and subthalamic nucleus. It is important to note, however, that the dorsal striatum and globus pallidus may be considered anatomically distinct from the substantia nigra, nucleus accumbens, and subthalamic nucleus. Each of these components has a complex internal anatomical and neurochemical organization. The largest component, the striatum (dorsal and ventral), receives input from many brain areas beyond the basal ganglia, but only sends output to other components of the basal ganglia. The pallidum receives input from the striatum, and sends inhibitory output to a number of motor-related areas. The substantia nigra is the source of the striatal input of the neurotransmitter dopamine, which plays an important role in basal ganglia function. The subthalamic nucleus receives input mainly from the striatum and cerebral cortex, and projects to the globus pallidus.
Currently, popular theories implicate the basal ganglia primarily in action selection; that is, it helps determine the decision of which of several possible behaviors to execute at any given time. In more specific terms, the basal ganglia's primary function is likely to control and regulate activities of the motor and premotor cortical areas so that voluntary movements can be performed smoothly. Experimental studies show that the basal ganglia exert an inhibitory influence on a number of motor systems, and that a release of this inhibition permits a motor system to become active. The "behavior switching" that takes place within the basal ganglia is influenced by signals from many parts of the brain, including the prefrontal cortex, which plays a key role in executive functions.
The importance of these subcortical nuclei for normal brain function and behavior is emphasized by the numerous and diverse neurological conditions associated with basal ganglia dysfunction, which include: disorders of behavior control such as Tourette syndrome, hemiballismus, and obsessive–compulsive disorder; dystonia; addiction; and movement disorders, the most notable of which are Parkinson's disease, which involves degeneration of the dopamine-producing cells in the substantia nigra pars compacta, and Huntington's disease, which primarily involves damage to the striatum. The basal ganglia have a limbic sector whose components are assigned distinct names: the nucleus accumbens, ventral pallidum, and ventral tegmental area (VTA). There is considerable evidence that this limbic part plays a central role in reward learning, particularly a pathway from the VTA to the nucleus accumbens that uses the neurotransmitter dopamine. A number of highly addictive drugs, including cocaine, amphetamine, and nicotine, are thought to work by increasing the efficacy of this dopamine signal. There is also evidence implicating overactivity of the VTA dopaminergic projection in schizophrenia.
In terms of development, the human nervous system is often classified based on the original 3 primitive vesicles from which it develops: These primary vesicles form in the normal development of the neural tube of the human fetus and initially include prosencephalon, mesencephalon, and rhombencephalon, in rostral to caudal (from head to tail) orientation. Later in development of the nervous system each section itself turns into smaller components. During development, the cells that migrate tangentially to form the basal ganglia are directed by the lateral and medial ganglionic eminences. The following table demonstrates this developmental classification and traces it to the anatomic structures found in the basal ganglia. The structures relevant to the basal ganglia are shown in bold.
|Primary division of the neural tube||Secondary subdivision||Final segments in a human adult|
The basal ganglia form a fundamental component of the cerebrum. In contrast to the cortical layer that lines the surface of the forebrain, the basal ganglia are a collection of distinct masses of gray matter lying deep in the brain not far from the junction of the thalamus. Like most parts of the brain, the basal ganglia consist of left and right sides that are virtual mirror images of each other.
In terms of anatomy, the basal ganglia are divided by anatomists into four distinct structures, depending on how superior or rostral they are (in other words depending on how close to the top of the head they are): Two of them, the striatum and the pallidum, are relatively large; the other two, the substantia nigra and the subthalamic nucleus, are smaller. In the illustration to the right, two coronal sections of the human brain show the location of the basal ganglia components. Of note, and not seen in this section, the subthalamic nucleus and substantia nigra lie farther back (posteriorly) in the brain than the striatum and pallidum.
The striatum is the largest component of the basal ganglia. The term "striatum" comes from the observation that this structure has a striped appearance when sliced in certain directions, arising from numerous large and small bundles of nerve fibers (white matter) that traverse it. Early anatomists, examining the human brain, perceived the dorsal striatum as two distinct masses of gray matter separated by a large tract of white matter called the internal capsule. They named these two masses the "caudate nucleus" and "putamen". More recent anatomists have concluded, on the basis of microscopic and neurochemical studies, that it is more appropriate to consider these masses as two separated parts of a single entity, the "dorsal striatum", in the same way that a city may be separated into two parts by a river. Numerous functional differences between the caudate and putamen have been identified, but these are taken to be consequences of the fact that each sector of the dorsal striatum is preferentially connected to specific parts of the cerebral cortex.
The internal organization of the striatum is extraordinarily complex. The vast majority of striatal neurons (about 96%) are a class of projection neurons known as medium spiny neurons. These neurons are GABAergic cells (meaning that they release the neurotransmitter gamma-aminobutyric acid, a.k.a. GABA) with small cell bodies and dendrites densely covered with dendritic spines, which receive synaptic input primarily from the cortex and thalamus. Medium spiny neurons can be divided into subtypes in a number of ways, on the basis of neurochemistry and connectivity. The next most abundant classes of neurons in the striatum are cholinergic interneurons (roughly 2%) and GABAergic interneurons (roughly 2%).
Numerous studies have shown that the connections between cortex and striatum are, in general, topographic; that is, each part of the cortex sends stronger input to some parts of the striatum than to others. The nature of the topography has been difficult to understand, however—perhaps in part because the striatum is organized in three dimensions, whereas the cortex, as a layered structure, is organized in two. This dimensional discrepancy entails a great deal of distortion and discontinuity in mapping one structure to the other. It is interesting to note that the same topography applies to the striatal connections to the thalamus.
The pallidum consists of a large structure called the globus pallidus ("pale globe") together with a smaller ventral extension called the ventral pallidum. The globus pallidus appears as a single neural mass, but can be divided into two functionally distinct parts, called the internal (or medial) and external (lateral) segments, abbreviated GPi and GPe. Both segments contain primarily GABAergic neurons, which therefore have inhibitory effects on their targets. The two segments participate in distinct neural circuits. The external segment, or GPe, receives input mainly from the striatum, and projects to the subthalamic nucleus. The internal segment, or GPi, receives signals from the striatum via two pathways, called "direct" and "indirect". Pallidal neurons operate using a disinhibition principle. These neurons fire at steady high rates in the absence of input, and signals from the striatum cause them to pause or reduce their rate of firing. Because pallidal neurons themselves have inhibitory effects on their targets, the net effect of striatal input to the pallidum is a reduction of the tonic inhibition exerted by pallidal cells on their targets (disinhibition) with an increased rate of firing in the targets.
The substantia nigra is a mesencephalic gray matter portion of the basal ganglia that is divided into SNr (reticulata) and SNc (compacta). SNr often works in unison with GPi, and the SNr-GPi complex inhibits the thalamus. Substantia nigra pars compacta (SNc) however, produces the neurotransmitter dopamine, which is very significant in maintaining balance in the striatal pathway. The circuit portion below explains the role and circuit connections of each of the components of the basal ganglia.
The subthalamic nucleus (STN) is a diencephalic gray matter portion of the basal ganglia, and the only portion of the ganglia that produces an excitatory neurotransmitter, glutamate. The role of the subthalamic nucleus is to stimulate the SNr-GPi complex and it is part of the indirect pathway. The subthalamic nucleus receives inhibitory input from the external part of the globus pallidus and sends excitatory input to the GPi.
Multiple models have been proposed relating to circuit definition and relating the basal ganglia to its many functions. There is currently debate among the pathway divisions, pathway overlap, and pathway regulation. The circuity definition has evolved since the first proposed definition in the 1990s by Delong in the parallel processing model, in which the cortex and substantia nigra pars compacta project into the dorsal striatum giving rise to an inhibitory indirect and excitatory direct pathway. The inhibitory indirect pathway involved the inhibition of the globus pallidus externus, allowing for the disinhibition of the globus pallidus internus allowing it to inhibit the thalamus. The direct or excitatory pathway involved the disinhibition of the thalamus through the inhibition of the GPe/SNr. However the speed of the direct pathway would not be concordant with the indirect pathway in this model leading to problems with it. To get over this, a hyperdirect pathway where the cortex sends glutaminergic projections through the subthalamic nucleus exciting the inhibitory GPe under the center surround model, as well as a shorter indirect pathway have been proposed. Generally, the basal ganglia circuitry is divided into limbic, associative(prefrontal), oculomotor and motor pathways. The motor and oculomotor are sometimes grouped into one motor pathway. However, more subdivisions of loops have been proposed, up to 20,000.
The direct pathway, originating in the dorsal striatum inhibits the GPe and SNr, resulting in a net disinhibition or excitation of the thalamus. This pathway consist of medium spiny neurons (MSNs) that express dopamine receptor D1, muscarinic acetylcholine receptor M4, and adenosine receptor A1. The direct pathway has been proposed to facilitate motor actions, timing of motor actions, gating of working memory, and motor responses to specific stimuli.
The (long) indirect pathway originates in the dorsal striatum and inhibits the GPi, resulting in disinhibition of the GPe which is then free to inhibit the thalamus. This pathway consists of MSNs that express dopamine receptor D2, muscarinic acetylcholine receptor M1, and adenosine receptor A2a. This pathway has been proposed to result in global motor inhibition(inhibition of all motor activity), and termination of responses. Another shorter indirect pathway has been proposed, which involves cortical excitation of the subthalamic nucleus resulting in direct excitation of the GPe, and inhibition of the thalamus. This pathway is proposed to result in inhibition of specific motor programs based off of associative learning.
A combination of these indirect pathways resulting in a hyperdirect pathway that results in inhibition of basal ganglia inputs besides one specific focus has been proposed as part of the center surround theory. This hyperdirect pathway is proposed to inhibit premature responses, or globally inhibit the basal ganglia to allow for more specific top down control by the cortex.
The interactions of these pathways are currently under debate. Some say that all pathways directly antagonize each other in a "push pull" fashion, while others support the center surround theory, in which one focused input into the cortex is protected by inhibition of competing inputs by the rest of the indirect pathways.
The basal ganglia contains many afferent glutaminergic inputs, with predominantly GABAergic efferent fibers, modulatory cholinergic pathways, significant dopamine in the pathways originating in the ventral tegmental area and substantia nigra, as well as various neuropeptides. Neuropeptides found in the basal ganglia include substance P, neurokinin A, cholecystokinin, neurotensin, neurokinin B, neuropeptide y, somatostatin, dynorphin, enkephaline. Other neuromodulators found in the basal ganglia include nitric oxide, carbon monoxide, and phenylethylamine.
One intensively studied functions of the basal ganglia (BG) is its role in controlling eye movements. Eye movement is influenced by an extensive network of brain regions that converge on a midbrain area called the superior colliculus (SC). The SC is a layered structure whose layers form two-dimensional retinotopic maps of visual space. A "bump" of neural activity in the deep layers of the SC drives an eye movement directed toward the corresponding point in space.
The SC receives a strong inhibitory projection from the BG, originating in the substantia nigra pars reticulata (SNr). Neurons in the SNr usually fire continuously at high rates, but at the onset of an eye movement they "pause", thereby releasing the SC from inhibition. Eye movements of all types are associated with "pausing" in the SNr; however, individual SNr neurons may be more strongly associated with some types of movements than others. Neurons in some parts of the caudate nucleus also show activity related to eye movements. Since the great majority of caudate cells fire at very low rates, this activity almost always shows up as an increase in firing rate. Thus, eye movements begin with activation in the caudate nucleus, which inhibits the SNr via the direct GABAergic projections, which in turn disinhibits the SC.
Extracellular dopamine in the basal ganglia has been linked to motivational states in rodents, with high levels being linked to satiated "euphoria", medium levels with seeking, and low with aversion. The limbic basal ganglia circuits are influenced heavily by extracellular dopamine. Increased dopamine results in inhibition of the Ventral pallidum, entopeduncular nucleus, and substantia nigra pars reticulata, resulting in disinhibition of the thalamus. This model of direct D1, and indirect D2 pathways explain why selective agonists of each receptor are not rewarding, as activity at both pathways is required for disinhibition. The disinhibition of the thalamus leads to activation of the prefrontal cortex and ventral striatum, selective for increased D1 activity leading to reward.
Two models have been proposed for the basal ganglia, one being that actions are generated by a "critic" in the ventral striatum and estimates value, and the actions are carried out by an "actor" in the dorsal striatum. Another model proposes the basal ganglia acts as a selection mechanism, where actions are generated in the cortex and are selected based on context by the basal ganglia. The CBGTC loop is also involved in reward discounting, with firing increasing with an unexpected or greater than expected reward. One review supported the idea that the cortex was involved in learning actions regardless of their outcome, while the basal ganglia was involved in selecting appropriate actions based off of associative reward based trial and error learning.
The basal ganglia has been proposed to gate what enters and what doesn't enter working memory. One hypothesis proposes that the direct pathway(Go, or excitatory) allows information into the PFC, where is stays independent of the pathway, however another theory proposes that in order for information to stay in the PFC the direct pathway needs to continue reverberating. The short indirect pathway has been proposed to, in a direct push pull antagonism with the direct pathway, close the gate to the PFC. Together these mechanisms regulate working memory focus.
The following is a list of disorders that have been linked to the basal ganglia:
The acceptance that the basal ganglia system constitutes one major cerebral system took time to arise. The first anatomical identification of distinct subcortical structures was published by Thomas Willis in 1664. For many years, the term corpus striatum was used to describe a large group of subcortical elements, some of which were later discovered to be functionally unrelated. For many years, the putamen and the caudate nucleus were not associated with each other. Instead, the putamen was associated with the pallidum in what was called the nucleus lenticularis or nucleus lentiformis.
A thorough reconsideration by Cécile and Oskar Vogt (1941) simplified the description of the basal ganglia by proposing the term striatum to describe the group of structures consisting of the caudate nucleus, the putamen, and the mass linking them ventrally, the nucleus accumbens. The striatum was named on the basis of the striated (striped) appearance created by radiating dense bundles of striato-pallido-nigral axons, described by anatomist Samuel Alexander Kinnier Wilson (1912) as "pencil-like".
The anatomical link of the striatum with its primary targets, the pallidum and the substantia nigra, was discovered later. The name globus pallidus was attributed by Déjerine to Burdach (1822). For this, the Vogts proposed the simpler "pallidum". The term "locus niger" was introduced by Félix Vicq-d'Azyr as tache noire in (1786), though that structure has since become known as the substantia nigra, due to contributions by Von Sömmering in 1788. The structural similarity between the substantia nigra and globus pallidus was noted by Mirto in 1896. Together, the two are known as the pallidonigral ensemble, which represents the core of the basal ganglia. Altogether, the main structures of the basal ganglia are linked to each other by the striato-pallido-nigral bundle, which passes through the pallidum, crosses the internal capsule as the "comb bundle of Edinger", then finally reaches the substantia nigra.
Additional structures that later became associated with the basal ganglia are the "body of Luys" (1865) (nucleus of Luys on the figure) or subthalamic nucleus, whose lesion was known to produce movement disorders. More recently, other areas such as the central complex (centre médian-parafascicular) and the pedunculopontine complex have been thought to be regulators of the basal ganglia.
Near the beginning of the 20th century, the basal ganglia system was first associated with motor functions, as lesions of these areas would often result in disordered movement in humans (chorea, athetosis, Parkinson's disease).
The nomenclature of the basal ganglia system and its components has always been problematic. Early anatomists, seeing the macroscopic anatomical structure but knowing nothing of the cellular architecture or neurochemistry, grouped together components that are now believed to have distinct functions (such as the internal and external segments of the globus pallidus), and gave distinct names to components that are now thought to be functionally parts of a single structure (such as the caudate nucleus and putamen).
The term "basal" comes from the fact that most of its elements are located in the basal part of the forebrain. The term ganglia is a misnomer: In modern usage, neural clusters are called "ganglia" only in the peripheral nervous system; in the central nervous system they are called "nuclei". For this reason, the basal ganglia are also occasionally known as the "basal nuclei". Terminologia anatomica (1998), the international authority for anatomical naming, retained "nuclei basales", but this is not commonly used.
The International Basal Ganglia Society (IBAGS) informally considers the basal ganglia to be made up of the striatum, the pallidum (with two nuclei), the substantia nigra (with its two distinct parts), and the subthalamic nucleus. Percheron et al. in 1991 and Parent and Parent in 2005 included the central region (centre median-parafascicular) of the thalamus as part of the basal ganglia, while Mena-Segovia et al. in 2004 included the pedunculopontine complex as well.
Also, the names given to the various nuclei of the basal ganglia are different in different species. In particular, the internal segment of the globus pallidus in primates is called the entopeduncular nucleus in rodents. The "striatum" and "external segment of the globus pallidus" in primates are called the "paleostriatum augmentatum" and "paleostriatum primitivum," respectively, in birds.
The basal ganglia form one of the basic components of the forebrain, and can be recognized in all species of vertebrates. Even in the lamprey (generally considered one of the most primitive of vertebrates), striatal, pallidal, and nigral elements can be identified on the basis of anatomy and histochemistry.
A clear emergent issue in comparative anatomy of the basal ganglia is the development of this system through phylogeny as a convergent cortically re-entrant loop in conjunction with the development and expansion of the cortical mantle. There is controversy, however, regarding the extent to which convergent selective processing occurs versus segregated parallel processing within re-entrant closed loops of the basal ganglia. Regardless, the transformation of the basal ganglia into a cortically re-entrant system in mammalian evolution occurs through a re-direction of pallidal (or "paleostriatum primitivum") output from midbrain targets such as the superior colliculus, as occurs in sauropsid brain, to specific regions of the ventral thalamus and from there back to specified regions of the cerebral cortex that form a subset of those cortical regions projecting into the striatum. The abrupt rostral re-direction of the pathway from the internal segment of the globus pallidus into the ventral thalamus—via the path of the ansa lenticularis—could be viewed as a footprint of this evolutionary transformation of basal ganglia outflow and targeted influence.
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