The basal ganglia system is one major cerebral system only recently reconstituted. A part of it was presented as "motor", "extrapyramidal", complementary to the corticospinal (pyramidal). Contrary to what was thought, the basal ganglia sytem has no direct spinal output. The motor effects are exerted through the motor cortex and the pyramidal system. The unilateral effects are thus controlateral.

Definition and content

The term ganglion should  be avoided in the central nervous system. Terminologia anatomica (1998), the international authority for anatomical naming indeed retain "nuclei basales" (p.130) but there is a "pars basalis telencephali" p. 129, which comprises the amygdala and some basal ganglia. The adjective basal describes the position in the basal part of the brain. The International Basal Ganglia Society, IBAGS, deals with cerebral parts and systems for which there is a consensus. This comprises the striatum, the pallidum (with two nuclei), the substantia nigra and the nucleus subthalamicus, to which is added the central complex (centre median parafascicular) and sometimes the pedunculopontine complex. This ensemble must not be seen as a collection but as a system.

Corticostriatal connection

The whole system starts as a major output of the cortex, about the same size as the corticopontine system opening the door to the cerebellar system. The cortico-striatal connection represents a significant portion of the cortical output. Almost every part of the cortex, except for the primary visual and auditory cortices, from the pyramidal neurons of the layer V send axons to the striatum. The topography of the cortico-striate connection is not simple as as small cortical place can send terminal arborisations to several striatal places (Goldman and Nauta, 19 Selemon and Goldman-Rakic)

Basal ganglia core

The basal ganglia core includes the striatum and its direct targets reached through the striato-pallido-nigral bundle: the two nuclei of the pallidum and the substantia nigra.

Striatum

The striatum is a huge neuronal telencephalic mass located close to the lateral cerebral ventricles. In primates, it has four neuronal genera: spiny (96%), leptodendritic (2%), spidery (1%) neurons and microneurons(1%) ^[1]. The dendritic arborisations of the spiny neurons are spherical. Their diameter depends on the animal species. [[Dendritic spine|Spines] are of the same type than those of two other (telencephalic) acanthodendritic (acanthos means spine) genera, the pyramidal neurons of the cerebral cortex and the spiny neurons of the amygdala. Most of these spines synapse with cortical afferents. Their axons have abundant and dense initial axonal collateral participating in local circuitry. The further part is long and myelinated. The neurons are GABAergic. The leptodendritic neurons (or Deiter's) have all the morphological properties of the pallidal neurons. The spidery neurons are specific to primates. They have a big soma and short dendritic and axonal branches. They are the cholinergic neurons of the primate, with a morphology entirely different from that of the cholinergic neurons of non-primates. They are the "tonically active neurons" or TANS of Kimura and collaborators. The microneurons are local circuit neurons similar to those found in the thalamus for instance. They are GABAergic, and some may be dopaminergic ^[2]. The distribution of these neurons is assessed to be biphasic either in the matrix or in striosomes. This opposition is not clear everywhere. In opposition to the head of the caudate, every striatal part has not distinct striosomes. These would represent insular segregation of orbitofrontal axonal endings. They have no relation in macaques with amygdalar afferents. The long oblique split of the striatum by the internal capsule creates the classic division into putamen, caudate and fundus, that do not to correspond exactly with the presently accepted anatomofunctional subdivision of the striatum. Due to a separation of corticostriate territories, a sensorimotor territory (or sensorimotor striatum) may be distinguished. It receives axons from the central region of the cortex, primary somatosensory, motor, premotor, accessory motor and anterior parietal. It is essentially putaminal, but does not cover the total extent of the putamen. Conversely it includes intracapsular fringes and the inferolateral border of the caudate ^[3]. To this is opposed an associative territory. This is essentially caudate above all orally and dorsally but does not cover the entire caudate volume. The separation between the two may be clearcut and observe using calbinding immunochemistry (the sensorimotor territory being negative)^[4]. The isolation of a third ventral striatal part is more difficult. One part is only is distinctive the "nucleus accumbens" having same morphological features but particular immunostaining. It selectively receives axons from the subiculum.

The striato-pallido-nigral bundle. This is made up of very numerous thin, fewly myelinated axons from the above described spiny neurons. Dispute about whether each striatal axon has a single target has been resolved recently^[5]. Striatal neurons in primates may have several targets. A non-negligable number of them send axons to all three targets.The main mediator is GABA, but there is one (or several) comediator that varies depending on the target. This is the case for enkephalin in the lateral pallidum and substance P in the medial ^[6]. The substantia nigra receives a mixture of the two. This would mean that a single axon is able to differentiate parts according to the target. This considerably modifies several decades old schemes.

Pallido-nigral ensemble

This comprises the two nuclei of the pallidum  and the pars lateralis and the pars reticulata of the "substantia" nigra (TA, yet not a substance but a nucleus). By no ways has the pallidum of the shape of a globus. Cecile and Oskar Vogt (1941) simplified the case by selecting pallidum, also offered by the Terminologia Anatomica (1998). The whole set is made up the same neuronal components. The majority is made up of large neurons, strongly stained for parvalbumin, having very large dendritic arborisations (much larger in primates than in rodents) with straight and thick dendrites of the leptodendritic family (Yelnik et al. 1987). Only the shape and direction of the dendritic arborizations differ in pallidum and nigra. In the pallidum, the threee-dimensional shape of arborisations is discoid and flat. The arborisations are parallel to one other and to the lateral border of the pallidum. They are thus perpendicular to the striatal afferences. As they have very large extensions they may thus have contact with a large quantity of striatal axons. The synaptology of the set is uncommon. The dendrites of the pallidal or nigral axons are entirely covered by synapses without any apposition of glia. More than 90% of synapses are from striatal origin (Di Figlia et al. )

Lateral pallidum (external segment globus pallidus, GPe)

sends most of its axons to the subthalamic nucleus from which it receives a feed-back connection.

Medial pallidum ( internal segment globus pallidus, GPi)

In addition to the massive striatopallidal connection the medial pallidum receives a dopamine innervation from the nigra compacta. It sends its axons to the lateral region of the thalamus (VO), the pars media of the central complex (see below) and the pedunculopontine complex.

Nigrapars lateralis (SNl)

The two parts of the nigra that belong to the basal ganglia core are the pars lateralis and the pars reticulata receiving a dense projection from the striato-pallido-nigral bundle and having the same structure as that of pallidal neurons. The difference between pallidal and nigral neurons is only in the three-dimensional extension of their dendritic arborizations. The particular synaptology is also the same. The pars lateralis is the most lateral part of the nigra; the main difference from the pars reticulata is that it sends axons to the superior colliculus.

=== Nigra pars reticulata (SNr)=== sends nigro-thalamic axons to the anterior most and medial part of the lateral region of the thalamus the nucleus ventralis anterior (VA, differentiated from VO receiving pallidal afferences).

Striato-pallidonigral connection

Nigral pars compacta (SNc) and nearby dopaminergic elements

Sensu stricto, the pars compacta is a part of the core of basal anglia core since it receives directly synapses from striatal axons through the striatopallidonigral bundle. However, this afferent connection is probably less impotant (at least in physiopathological models) than its output. This explains its intermediate position in our plan. The dense and dark neurons of the pars compacta are the origin of the name , 'substantia nigra'. Aging indeed leads to its blackening, by deposit of melanin, visible by naked eye. Its constitution contrasts with the rest of the nigra. The neurons have larger and thicker dendritic arborizations. This is also the case for neurons located more dorsally and posteriorly that did not get a stable status. The long ventral dendrites of the pars compacta indeed plunge deep in the pars reticulata where they receive synapses from the striato-pallido-nigral bundle. The neurons are the dopaminergic neurons which have been the source of a considerabla literature. They end intensively in the striatum and also in almost all elements of the basal ganglia system: pallidum, subthalamic nucleus. The role of these dopaminergic neurons

Regulators of the basal ganglia core

Subthalamic nucleus, or corpus Lyuisi

The subthalamic nucleus is made up of a single neuronal species (with no known local circuit neurons) with rather long ellipsoid dendritic arborisations. The subthalamic nucleus receives its main afference from the lateral nucleus of the pallidum. Another afference comes from the cerebral cortex particularly the motor cortex, which is too neglected in the models. Subthalamic neurons leave the nucleus dorsally. Their targets are at first the elements of the core of the basal ganglia: the substantia nigra and the medial and lateral nuclei of the pallidum. The main afference of the nucleus is the lateral nucleus of the pallidum (external segment of the globus pallidus (GPe) with which it makes a tight regulatory loop ( STN-GPe circuit). It utilizes the excitatory neurotransmitter glutamate. This gives it a particular interest since the striatopallidal, and the pallido-subthalamic connections are inhibitory (GABA). This is over exploited in models. Stereotactic stimulation of the nucleus suppress most of the symptoms of the Parkinson' syndrome particularly sikinesia induced by dopatherapy.

Central complex (C)

The central complex is the so-called centre-médian- parafascicular complex. In upper primates, starting from the cercopithecidae, it is in fact made up not of two but of three parts. Two opposed interpretations were proposed by the Vogts (1941) and Niimi () concerning the belonging of the intermediate part either to the centre médian or to the parafascicular nucleus. This is undecidable. It has thus been proposed to group the three elements together in the regio Centralis and to name them from medially to laterally: n. centralis pars parafascicularis, pars media and pars paralateralis (the three with their own neuronal species). The whole is parvalbumin rich. The first two medial parts are acetylcholinesterase rich. They are the source of the major, centralo-striatal, part of the thalamo-striatal connection, with glutamate as the mediator. The main afference of the pars media is the medial pallidum. This pars media sends axons to the sensorimotor striatum . The pars media is a part of the subcortical Nauta-Mehler's circuit (striatum-medial pallidum-pars media-striatum). The pars parafascicularis receives afferences from the substantia nigra and the superior colliculus. The pars parafascicularis sends axons to the associative striatum . The same sends also axons to the substantia nigra. There are thus strong interconnections of the complex with the basal ganglia. The pars paralateralis has essentially cortical relation particularly with the motor cortex. The structure of the complex is different from that of the close intralaminar formation. It has different connections. This leads today to remove the central complex from intralaminar elements and to link it to the basal ganglia complex. It may be classified among the regulators of the core. There were few physiological data. For Matsumoto et al. (2001) the axons of the complex would supply striatal neurons with information about behaviorally significant sensory events.

Amygdala

Amygdala is not an element of the basal ganglia. It intervenes in the basal ganglia system regulation at the striatal level. Its axons do not cover the whole extent of the striatum.

Pedunculopontine complex

The pedunculopontine complex is not a primary part of the basal ganglia. It is a part of the reticulate formation having strong interrelations with the basal ganglia system. As indicated by its name, it is located at the junction between the pons and the cerebral peduncle, lateral to the decussation of the brachium conjunctivum. It receives direct afferences from the medial pallidum. One part of its axons are cholinergic. It sends axons to the pallidal territory of the lateral region VO. A review on its role in the system and in diseases is given by Pahapill and Lozano (2000)

Outputs of the basal ganglia system

Many connections of the basal ganglia are between elements of the basal ganglia. There are few output external targets. One is the superior colliculus, from the nigra lateralis. There are two major distinct output subsystems in direction to the thalamus and from there to the cortex.

Nigra lateralis to superior colliculus

Medial pallidum to thalamic VO and cortex

Axons to the thalamus form the ansa lenticularis and the fasciculus lenticularis, forming a single entity. The axons arrive at the medial face of the pallidum; from there, they cross the internal capsule where they form the comb system (Kamm system of Edinger, 1900). The axons arrives at the lateral border of the subthalamic nucleus. Passing over it they constitute the field H2 of Forel (1877). From there, they curve down towards the hypothalamus. At field H, they turn abruptly and go up in a dorsolateral direction (forming H1 field) and reach the ventral border of the thalamus. Pallidal axons have their own thalamic territory, everywhere separated from the cerebellar and from the nigral. To mark this separation the nucleus is named nucleus ventralis oralis (VO) and the nigral VA ^[7]. The VO nucleus remains lateral in macaques and human. It stained for calbindin and acetylcholonesterase. The thalamocortical neurons of VO go preferently to the supplementary motor cortex (SMA), to preSMA and to a lesser extent to the motor cortex. The pallidothalamic neurons also give branches to the pars media of the central complex (see above). This sends axons to the premotor, accessory motor cortex.

Nigra reticulata to thalamic VA and cortex

Axons go up dorsally without forming a clear bundle. They reach the inferior border of the thalamus. The nigral territory (VA) is medial to the pallidal. It is crossed by the mammillothalamic bundle. In addition to the nigral afference, it receives axons from the tectum (superior colliculus) and from the amygdala (basal complex). Thalamocortical axons from VA send their axons to a particular set made up of the oculomotor cortex (FEF and SEF), the frontal and the cingular cortex. This indicates that this output subsystem participate in visuomotor circuits.

The target motor areas send back axons to the striatum forming thus cortico-basal ganglia- thalamus- cortical longer circuits.

Models of the basal ganglia system

The description done above is essentially anatomical and follows a simple topological hierarchical rule.

References

^ Yelnik et al. (1991)
^ Rochette et al.
^ Percheron et al. (1984)
^ François et al. (19 )
^ Levesque and Parent et al. (2005)
^ Haber and Elde (1981)
^ ;Percheron, (2003)

Cossette, M., Lecomte, F., Parent, A. (2005) Morphology and didtribution of dopaminergic intrinsic to the human striatum. J.Chem. Neuroanat.,29: 1-11
diFiglia, M
François
Goldman and Nauta
Levesque, M., Bédard, A., Cossette, M., Parent, A. (2003) Novel aspets of the chimical anatomy of the striatum and its efferent projections. . Chem. Neuroanat. 26: 271-281

Levesque, M. and Parent, A. (2005) The striatofugal fiber system in primates:a reevaluationof its organization based on single-axon tracin studies. PNAS.102: Matsumoto, N., Minamimoto, T, Graybiel, A.M, Kimura, M. (2001) Neurons in the thalmic CN-Pf complex supply striatal neurons with information about behaviorally significant sensory events. J. Neurophysiol. 85: 960-976

Niimi
Pahapill, P.A. and Lozano, A. M. (2000) The pedunculopontine nucleus and Parkinson's disease. Brain, 123:1767-1783
Percheron, G. (2003) Thalamus. In The human nervous system. Paxinos, G. and Mai, J. eds) Elsevier, Amsterdam
Selemon and Goldman Rakic
Terminologia anatomica (1998) Thieme, Stuttgart
Vogt, C. and O. (1941)
Yelnik, J., François, Percheron, G?, Tandé, D. (1991) Morphological taxonomy of the neurons of the primate striatum. J. Comp. Neurol. 313:273 .

[1] Yelnik et al. (1991)

[2] Rochette et al.

[3] Percheron et al. (1984)

[4] François et al. (19 )

[5] Levesque and Parent et al. (2005)

[6] Haber and Elde (1981)

[7] ;Percheron, (2003)

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