Basal ganglia

From Wikipedia, the free encyclopedia

Basal ganglia
Basal ganglia labeled at top right.
Basal ganglia on underneath view of brain
Details
Part of	Cerebrum
Identifiers
Latin	nuclei basales
MeSH	D001479
NeuroNames	224, 2677
NeuroLex ID	birnlex_826
TA	A14.1.09.501
FMA	84013

The basal ganglia (or basal nuclei) are a group of subcortical nuclei, of varied origin, in the brains of vertebrates, including humans, which are situated at the base of the forebrain and top of the midbrain. There are some differences in the basal ganglia of primates. Basal ganglia 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, habit learning, eye movements, cognition, and emotion.

The main components of the basal ganglia – as defined functionally – are the striatum; both dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle), globus pallidus, ventral pallidum, substantia nigra, 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.

Popular theories implicate the basal ganglia primarily in action selection – in helping to decide 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 basal ganglia are of major importance for normal brain function and behaviour. Their dysfunction results in a wide range of neurological conditions including disorders of behaviour control and movement. Those of behaviour include Tourette syndrome, obsessive–compulsive disorder, and addiction. Movement disorders include, most notably Parkinson's disease, which involves degeneration of the dopamine-producing cells in the substantia nigra, Huntington's disease, which primarily involves damage to the striatum, dystonia, and more rarely hemiballismus. 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 as well as cognition and frontal lobe functioning, via the mesolimbic pathway from the VTA to the nucleus accumbens that uses the neurotransmitter dopamine, and the mesocortical pathway. 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.

Structure

In terms of development, the human central nervous system is often classified based on the original three primitive vesicles from which it develops: These primary vesicles form in the normal development of the neural tube of the embryo and initially include the 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
Prosencephalon	Telencephalon Diencephalon	On each side of the brain: the cerebral cortices, caudate, putamen Globus pallidus, ventral pallidum, thalamus, subthalamus, epithalamus, hypothalamus, subthalamic nucleus
Mesencephalon	Mesencephalon	Mesencephalon (midbrain): substantia nigra pars compacta (SNc), substantia nigra pars reticulata (SNr)
Rhombencephalon	Metencephalon Myelencephalon	Pons and cerebellum Medulla

Coronal slices of human brain showing the basal ganglia. White matter is shown in dark gray, gray matter is shown in light gray.
Anterior: striatum, globus pallidus (GPe and GPi)
Posterior: subthalamic nucleus (STN), substantia nigra (SN)

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. They lie to the side of and surround 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 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.

Striatum

Basal ganglia

 

The striatum is a subcortical structure generally divided into the dorsal striatum and ventral striatum, although a medial lateral classification has been suggested to be more relevant behaviorally^[10] and is being more widely used.

The striatum is composed mostly of medium spiny neurons. These GABAergic neurons project to the external (lateral) globus pallidus and internal (medial) globus pallidus as well as the substantia nigra pars reticulata. The projections into the globus pallidus and substantia nigra are primarily dopaminergic, although enkephalin, dynorphin and substance P are expressed. The striatum also contains interneurons that are classified into nitrergic neurons (due to use of nitric oxide as a neurotransmitter), tonically active cholinergic interneurons, parvalbumin-expressing neurons and calretinin-expressing neurons. The dorsal striatum receives significant glutamatergic inputs from the cortex, as well as dopaminergic inputs from the substantia nigra pars compacta. The dorsal striatum is generally considered to be involved in sensorimotor activities. The ventral striatum receives glutamatergic inputs from the limbic areas as well as dopaminergic inputs from the VTA, via the mesolimbic pathway. The ventral striatum is believed to play a role in reward and other limbic functions. The dorsal striatum is divided into the caudate and putamen by the internal capsule while the ventral striatum is composed of the nucleus accumbens and olfactory tubercle. The caudate has three primary regions of connectivity, with the head of the caudate demonstrating connectivity to the prefrontal cortex, cingulate cortex and amygdala. The body and tail show differentiation between the dorsolateral rim and ventral caudate, projecting to the sensorimotor and limbic regions of the striatum respectively. Striatopallidal fibres connect the striatum to the pallidus.

Pallidum

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 GPe receives input mainly from the striatum, and projects to the subthalamic nucleus. The GPi receives signals from the striatum via the "direct" and "indirect" pathways. 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.

Substantia nigra

Location of the substantia nigra within the basal ganglia

 

The substantia nigra is a midbrain gray matter portion of the basal ganglia that has two parts – the pars compacta (SNc) and the pars reticulata (SNr). 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.

Subthalamic nucleus

The subthalamic nucleus 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.

Circuit connections

Connectivity diagram showing excitatory glutamatergic pathways as red, inhibitory GABAergic pathways as blue, and modulatory dopaminergic pathways as magenta. (Abbreviations: GPe: globus pallidus external; GPi: globus pallidus internal; STN: subthalamic nucleus; SNc: substantia nigra pars compacta; SNr: substantia nigra pars reticulata)

 

Connectivity of the basal ganglia as revealed by diffusion spectrum imaging based on thirty subjects from the Human Connectome Project. Direct, indirect and hyperdirect pathways are visualized in different colors (see legend). Subcortical structures are rendered based on the Harvard-Oxford subcortical thalamus as well as the Basal Ganglia atlas (other structures). Rendering was generated using TrackVis software.

 

The left side of Fig.1 shows a region of the prefrontal cortex receiving multiple inputs from other regions, as cortico-cortical activity. The input from B is the strongest of these. The right side of Fig. 1 shows the input signals also being fed to the basal ganglia circuitry. The output from here, back to the same region, is shown to modify the strength of the input from B, by adding strength to the input from C thereby modifying the strongest signal from B to C. (Thalamic involvement is implicit but not shown).

 

Multiple models of basal ganglia circuits and function have been proposed, however there have been questions raised about the strict divisions of the direct and indirect pathways, their possible overlap and regulation. The circuitry model has evolved since the first proposed model 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 (through STN) allowing it to inhibit the thalamus.
• The direct or excitatory pathway involved the disinhibition of the thalamus through the inhibition of the GPi/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 glutamatergic 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 five pathways: one limbic, two associative (prefrontal), one oculomotor, and one motor pathway. (The motor and oculomotor pathways are sometimes grouped into one motor pathway.) The five general pathways are organized as follows:

• The motor loop involving projections from the supplementary motor area, arcuate premotor area, motor cortex and somatosensory cortex into the putamen, which projects into the ventrolateral GPi and caudolateral SNr which projects into the cortex through the ventralis lateralis pars medialis and ventralis lateralis pars orialis.
• The oculomotor loop involved projections from the frontal eye fields, the dorsolateral prefrontal cortex (DLPFC), and the posterior parietal cortex into the caudate, into the caudal dorsomedial GPi and ventrolateral SNr, finally looping back into the cortex through the lateral ventralis anterior pars magnocellularis(VAmc).
• The first cognitive/associative pathway proposes a pathway from the DLPFC, into the dorsolateral caudate, followed by a projection into the lateral dorsomedial GPi, and rostral SNr before projecting into the lateral VAmc and medial pars magnocellularis.
• The second cognitive/associative pathway proposed is a circuit projecting from the lateral orbitofrontal cortex, the temporal gyrus, and anterior cingulate cortex into the ventromedial caudate, followed by a projection into the lateromedial GPi, and rostrolateral SNr before looping into the cortex via the medial VAmc and medial magnocellularis.
• The limbic circuit involving the projections from the ACC, hippocampus, entorhinal cortex, and insula into the ventral striatum, then into the rostrodorsal GPi, ventral palladium and rostrodorsal SNr, followed by a loop back into the cortex through the posteromedial part of the medial dorsal nucleus. However, more subdivisions of loops have been proposed, up to 20,000.

The direct pathway, originating in the dorsal striatum inhibits the GPi 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 GPe, resulting in disinhibition of the GPi 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 on 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.

Diagram shows two coronal slices that have been superimposed to include the involved basal ganglia structures. Green arrows (+) refer to excitatory glutamatergic pathways, red arrows (–) refer to inhibitory GABAergic pathways and turquoise arrows refer to dopaminergic pathways that are excitatory on the direct pathway and inhibitory on the indirect pathway.

Neurotransmitters

The basal ganglia contains many afferent glutamatergic 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.

Functional connectivity

The functional connectivity, measured by regional co-activation during functional neuroimaging studies, is broadly consistent with the parallel processing models of basal ganglia function. The putamen was generally coactivated with motor areas such as the supplementary motor area, caudal anterior cingulate cortex and primary motor cortex, while the caudate and rostral putamen were more frequently coactivated with the rostral ACC and DLPFC. The ventral striatum was significantly associated with the amygdala and hippocampus, which although was not included in the first formulations of basal ganglia models, has been an addition to more recent models.

Function

Eye movements

One intensively studied function of the basal ganglia is its role in controlling eye movements. Eye movement is influenced by an extensive network of brain regions that converges 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 basal ganglia, 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.

Role in motivation

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. There is also evidence from non-human primate and human electrophysiology studies that other basal ganglia structures including the globus pallidus internus and subthalamic nucleus are involved in reward processing.

Decision making

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 on associative reward based trial and error learning.

Working memory

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 it 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.

Clinical significance

Basal ganglia disease is a group of movement disorders that result from either excessive output from the basal ganglia to the thalamus – hypokinetic disorders, or from insufficient output – hyperkinetic disorders. Hypokinetic disorders arise from an excessive output from the basal ganglia, which inhibits the output from the thalamus to the cortex, and thus limits voluntary movement. Hyperkinetic disorders result from a low output from the basal ganglia to the thalamus which gives not enough inhibition to the thalamic projections to the cortex and thus gives uncontrolled/involuntary movements. Dysfunction of the basal ganglia circuitry can also lead to other disorders.

The following is a list of disorders that have been linked to the basal ganglia:

• Addiction
• Athetosis
• Athymhormic syndrome (PAP syndrome)
• Attention-deficit hyperactivity disorder (ADHD)
• Blepharospasm
• Bruxism
• Cerebral palsy: basal ganglia damage during second and third trimester of pregnancy
• Chorea
• Dystonia
• Fahr's disease
• Foreign accent syndrome (FAS)
• Huntington's disease
• Kernicterus
• Lesch–Nyhan syndrome
• Major Depressive Disorder 
• Obsessive-compulsive disorder
• Other anxiety disorders 
• PANDAS
• Parkinson's disease
• Spasmodic dysphonia
• Stuttering
• Sydenham's chorea
• Tardive dyskinesia, caused by chronic antipsychotic treatment
• Tourette's disorder
• Wilson's disease

History

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", and 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 centromedian nucleus 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).

Terminology

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, whereas Terminologia anatomica excludes the last two. Some neurologists have included the centromedian nucleus of the thalamus as part of the basal ganglia, and some have also included the pedunculopontine nucleus.

Other animals

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.

The names given to the various nuclei of the basal ganglia are different in different species. In cats and rodents the internal globus pallidus is known as the entopeduncular nucleus. In birds the striatum is called the paleostriatum augmentatum and the external globus pallidus is called the paleostriatum primitivum. 

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.

Spinal cord

From Wikipedia, the free encyclopedia

Spinal cord
The spinal cord (in yellow) connects the brain to nerves throughout the body.
Details
Part of	Central nervous system
Artery	spinal artery
Identifiers
Latin	medulla spinalis
MeSH	D013116
NeuroNames	22
TA	A14.1.02.001
FMA	7647

The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column. It encloses the central canal of the spinal cord, which contains cerebrospinal fluid. The brain and spinal cord together make up the central nervous system (CNS). In humans, the spinal cord begins at the occipital bone, passing through the foramen magnum and entering the spinal canal at the beginning of the cervical vertebrae. The spinal cord extends down to between the first and second lumbar vertebrae, where it ends. The enclosing bony vertebral column protects the relatively shorter spinal cord. It is around 45 cm (18 in) in men and around 43 cm (17 in) long in women. The diameter of the spinal cord ranges from 13 mm (¹⁄₂ in) in the cervical and lumbar regions to 6.4 mm (¹⁄₄ in) in the thoracic area.

The spinal cord functions primarily in the transmission of nerve signals from the motor cortex to the body, and from the afferent fibers of the sensory neurons to the sensory cortex. It is also a center for coordinating many reflexes and contains reflex arcs that can independently control reflexes. It is also the location of groups of spinal interneurons that make up the neural circuits known as central pattern generators. These circuits are responsible for controlling motor instructions for rhythmic movements such as walking.

Structure

Diagram of the spinal cord showing segments

 

The spinal cord is the main pathway for information connecting the brain and peripheral nervous system. Much shorter than its protecting spinal column, the human spinal cord originates in the brainstem, passes through the foramen magnum, and continues through to the conus medullaris near the second lumbar vertebra before terminating in a fibrous extension known as the filum terminale.

It is about 45 cm (18 in) long in men and around 43 cm (17 in) in women, ovoid-shaped, and is enlarged in the cervical and lumbar regions. The cervical enlargement, stretching from the C5 to T1 vertebrae, is where sensory input comes from and motor output goes to the arms and trunk. The lumbar enlargement, located between L1 and S3, handles sensory input and motor output coming from and going to the legs.

The spinal cord is continuous with the caudal portion of the medulla, running from the base of the skull to the body of the first lumbar vertebra. It does not run the full length of the vertebral column in adults. It is made of 31 segments from which branch one pair of sensory nerve roots and one pair of motor nerve roots. The nerve roots then merge into bilaterally symmetrical pairs of spinal nerves. The peripheral nervous system is made up of these spinal roots, nerves, and ganglia.

The dorsal roots are afferent fascicles, receiving sensory information from the skin, muscles, and visceral organs to be relayed to the brain. The roots terminate in dorsal root ganglia, which are composed of the cell bodies of the corresponding neurons. Ventral roots consist of efferent fibers that arise from motor neurons whose cell bodies are found in the ventral (or anterior) gray horns of the spinal cord. 

The spinal cord (and brain) are protected by three layers of tissue or membranes called meninges, that surround the canal . The dura mater is the outermost layer, and it forms a tough protective coating. Between the dura mater and the surrounding bone of the vertebrae is a space called the epidural space. The epidural space is filled with adipose tissue, and it contains a network of blood vessels. The arachnoid mater, the middle protective layer, is named for its open, spiderweb-like appearance. The space between the arachnoid and the underlying pia mater is called the subarachnoid space. The subarachnoid space contains cerebrospinal fluid (CSF), which can be sampled with a lumbar puncture, or "spinal tap" procedure. The delicate pia mater, the innermost protective layer, is tightly associated with the surface of the spinal cord. The cord is stabilized within the dura mater by the connecting denticulate ligaments, which extend from the enveloping pia mater laterally between the dorsal and ventral roots. The dural sac ends at the vertebral level of the second sacral vertebra.

In cross-section, the peripheral region of the cord contains neuronal white matter tracts containing sensory and motor axons. Internal to this peripheral region is the grey matter, which contains the nerve cell bodies arranged in the three grey columns that give the region its butterfly-shape. This central region surrounds the central canal, which is an extension of the fourth ventricle and contains cerebrospinal fluid. 

The spinal cord is elliptical in cross section, being compressed dorsolaterally. Two prominent grooves, or sulci, run along its length. The posterior median sulcus is the groove in the dorsal side, and the anterior median fissure is the groove in the ventral side.

Spinal cord segments

The human spinal cord is divided into segments where pairs of spinal nerves (mixed; sensory and motor) form. Six to eight motor nerve rootlets branch out of right and left ventro lateral sulci in a very orderly manner. Nerve rootlets combine to form nerve roots. Likewise, sensory nerve rootlets form off right and left dorsal lateral sulci and form sensory nerve roots. The ventral (motor) and dorsal (sensory) roots combine to form spinal nerves (mixed; motor and sensory), one on each side of the spinal cord. Spinal nerves, with the exception of C1 and C2, form inside the intervertebral foramen (IVF). These rootlets form the demarcation between the central and peripheral nervous systems.

A model of segments of the human spine and spinal cord, nerve roots can be seen extending laterally from the (not visible) spinal cord.

 

The grey column, (as three regions of grey columns) in the center of the cord, is shaped like a butterfly and consists of cell bodies of interneurons, motor neurons, neuroglia cells and unmyelinated axons. The anterior and posterior grey column present as projections of the grey matter and are also known as the horns of the spinal cord. Together, the grey columns and the gray commissure form the "grey H." 

The white matter is located outside of the grey matter and consists almost totally of myelinated motor and sensory axons. "Columns" of white matter carry information either up or down the spinal cord.

The spinal cord proper terminates in a region called the conus medullaris, while the pia mater continues as an extension called the filum terminale, which anchors the spinal cord to the coccyx. The cauda equina ("horse's tail") is a collection of nerves inferior to the conus medullaris that continue to travel through the vertebral column to the coccyx. The cauda equina forms because the spinal cord stops growing in length at about age four, even though the vertebral column continues to lengthen until adulthood. This results in sacral spinal nerves originating in the upper lumbar region. 

Within the CNS, nerve cell bodies are generally organized into functional clusters, called nuclei. Axons within the CNS are grouped into tracts. 

There are 31 spinal cord nerve segments in a human spinal cord:

• 8 cervical segments forming 8 pairs of cervical nerves (C1 spinal nerves exit the spinal column between the foramen magnum and the C1 vertebra; C2 nerves exit between the posterior arch of the C1 vertebra and the lamina of C2; C3–C8 spinal nerves pass through the IVF above their corresponding cervical vertebrae, with the exception of the C8 pair which exit between the C7 and T1 vertebrae)
• 12 thoracic segments forming 12 pairs of thoracic nerves
• 5 lumbar segments forming 5 pairs of lumbar nerves
• 5 sacral segments forming 5 pairs of sacral nerves
• 1 coccygeal segment

Spinal cord segments in some common species 

Species	Cervical	Thoracic	Lumbar	Sacral	Caudal/Coccygeal	Total
Dog	8	13	7	3	5	36
Cat	8	13	7	3	5	36
Cow	8	13	6	5	5	37
Horse	8	18	6	5	5	42
Pig	8	15/14	6/7	4	5	38
Human	8	12	5	5	1	31
Mouse	8	13	6	4	3	35

In the fetus, vertebral segments correspond with spinal cord segments. However, because the vertebral column grows longer than the spinal cord, spinal cord segments do not correspond to vertebral segments in the adult, particularly in the lower spinal cord. For example, lumbar and sacral spinal cord segments are found between vertebral levels T9 and L2, and the spinal cord ends around the L1/L2 vertebral level, forming a structure known as the conus medullaris.

Although the spinal cord cell bodies end around the L1/L2 vertebral level, the spinal nerves for each segment exit at the level of the corresponding vertebra. For the nerves of the lower spinal cord, this means that they exit the vertebral column much lower (more caudally) than their roots. As these nerves travel from their respective roots to their point of exit from the vertebral column, the nerves of the lower spinal segments form a bundle called the cauda equina. 

There are two regions where the spinal cord enlarges:

• Cervical enlargement – corresponds roughly to the brachial plexus nerves, which innervate the upper limb. It includes spinal cord segments from about C4 to T1. The vertebral levels of the enlargement are roughly the same (C4 to T1).
• Lumbar enlargement – corresponds to the lumbosacral plexus nerves, which innervate the lower limb. It comprises the spinal cord segments from L2 to S3 and is found about the vertebral levels of T9 to T12.

Development

Spinal cord seen in a midsection of a five-week-old embryo

 

Spinal cord seen in a midsection of a 3 month old fetus

 

The spinal cord is made from part of the neural tube during development. There are four stages of the spinal cord that arises from the neural tube: The neural plate, neural fold, neural tube, and the spinal cord. Neural differentiation occurs within the spinal cord portion of the tube. As the neural tube begins to develop, the notochord begins to secrete a factor known as Sonic hedgehog or SHH. As a result, the floor plate then also begins to secrete SHH, and this will induce the basal plate to develop motor neurons. During the maturation of the neural tube, its lateral walls thicken and form a longtitudinal groove called the sulcus limitans. This extends the length of the spinal cord into dorsal and ventral portions as well. Meanwhile, the overlying ectoderm secretes bone morphogenetic protein (BMP). This induces the roof plate to begin to secrete BMP, which will induce the alar plate to develop sensory neurons. Opposing gradients of such morphogens as BMP and SHH form different domains of dividing cells along the dorsal ventral axis. Dorsal root ganglion neurons differentiate from neural crest progenitors. As the dorsal and ventral column cells proliferate, the lumen of the neural tube narrows to form the small central canal of the spinal cord. The alar plate and the basal plate are separated by the sulcus limitans. Additionally, the floor plate also secretes netrins. The netrins act as chemoattractants to decussation of pain and temperature sensory neurons in the alar plate across the anterior white commissure, where they then ascend towards the thalamus. Following the closure of the caudal neuropore and formation of the brain's ventricles that contain the choroid plexus tissue, the central canal of the caudal spinal cord is filled with cerebrospinal fluid. 

Earlier findings by Viktor Hamburger and Rita Levi-Montalcini in the chick embryo have been confirmed by more recent studies which have demonstrated that the elimination of neuronal cells by programmed cell death (PCD) is necessary for the correct assembly of the nervous system.

Overall, spontaneous embryonic activity has been shown to play a role in neuron and muscle development but is probably not involved in the initial formation of connections between spinal neurons.

Blood supply

The spinal cord is supplied with blood by three arteries that run along its length starting in the brain, and many arteries that approach it through the sides of the spinal column. The three longitudinal arteries are the anterior spinal artery, and the right and left posterior spinal arteries. These travel in the subarachnoid space and send branches into the spinal cord. They form anastamoses (connections) via the anterior and posterior segmental medullary arteries, which enter the spinal cord at various points along its length. The actual blood flow caudally through these arteries, derived from the posterior cerebral circulation, is inadequate to maintain the spinal cord beyond the cervical segments.

The major contribution to the arterial blood supply of the spinal cord below the cervical region comes from the radially arranged posterior and anterior radicular arteries, which run into the spinal cord alongside the dorsal and ventral nerve roots, but with one exception do not connect directly with any of the three longitudinal arteries. These intercostal and lumbar radicular arteries arise from the aorta, provide major anastomoses and supplement the blood flow to the spinal cord. In humans the largest of the anterior radicular arteries is known as the artery of Adamkiewicz, or anterior radicularis magna (ARM) artery, which usually arises between L1 and L2, but can arise anywhere from T9 to L5. Impaired blood flow through these critical radicular arteries, especially during surgical procedures that involve abrupt disruption of blood flow through the aorta for example during aortic aneursym repair, can result in spinal cord infarction and paraplegia.

Function

Somatosensory organization

Spinal cord tracts.

 

Somatosensory organization is divided into the dorsal column-medial lemniscus tract (the touch/proprioception/vibration sensory pathway) and the anterolateral system, or ALS (the pain/temperature sensory pathway). Both sensory pathways use three different neurons to get information from sensory receptors at the periphery to the cerebral cortex. These neurons are designated primary, secondary and tertiary sensory neurons. In both pathways, primary sensory neuron cell bodies are found in the dorsal root ganglia, and their central axons project into the spinal cord. 

In the dorsal column-medial leminiscus tract, a primary neuron's axon enters the spinal cord and then enters the dorsal column. If the primary axon enters below spinal level T6, the axon travels in the fasciculus gracilis, the medial part of the column. If the axon enters above level T6, then it travels in the fasciculus cuneatus, which is lateral to the fasciculus gracilis. Either way, the primary axon ascends to the lower medulla, where it leaves its fasciculus and synapses with a secondary neuron in one of the dorsal column nuclei: either the nucleus gracilis or the nucleus cuneatus, depending on the pathway it took. At this point, the secondary axon leaves its nucleus and passes anteriorly and medially. The collection of secondary axons that do this are known as internal arcuate fibers. The internal arcuate fibers decussate and continue ascending as the contralateral medial lemniscus. Secondary axons from the medial lemniscus finally terminate in the ventral posterolateral nucleus (VPLN) of the thalamus, where they synapse with tertiary neurons. From there, tertiary neurons ascend via the posterior limb of the internal capsule and end in the primary sensory cortex.

The proprioception of the lower limbs differs from the upper limbs and upper trunk. There is a four-neuron pathway for lower limb proprioception. This pathway initially follows the dorsal spino-cerebellar pathway. It is arranged as follows: proprioceptive receptors of lower limb → peripheral process → dorsal root ganglion → central process → Clarke's column → 2nd order neuron → medulla oblogata (Caudate nucleus) → 3rd order neuron → VPLN of thalamus → 4th order neuron → posterior limb of internal capsule → corona radiata → sensory area of cerebrum.

The anterolateral system works somewhat differently. Its primary neurons axons enter the spinal cord and then ascend one to two levels before synapsing in the substantia gelatinosa. The tract that ascends before synapsing is known as Lissauer's tract. After synapsing, secondary axons decussate and ascend in the anterior lateral portion of the spinal cord as the spinothalamic tract. This tract ascends all the way to the VPLN, where it synapses on tertiary neurons. Tertiary neuronal axons then travel to the primary sensory cortex via the posterior limb of the internal capsule. 

Some of the "pain fibers" in the ALS deviate from their pathway towards the VPLN. In one such deviation, axons travel towards the reticular formation in the midbrain. The reticular formation then projects to a number of places including the hippocampus (to create memories about the pain), the centromedian nucleus (to cause diffuse, non-specific pain) and various parts of the cortex. Additionally, some ALS axons project to the periaqueductal gray in the pons, and the axons forming the periaqueductal gray then project to the nucleus raphes magnus, which projects back down to where the pain signal is coming from and inhibits it. This helps control the sensation of pain to some degree.

Motor organization

Actions of the spinal nerves

Level	Motor function
C1–C6	Neck flexors
C1–T1	Neck extensors
C3, C4, C5	Supply diaphragm (mostly C4)
C5, C6	Move shoulder, raise arm (deltoid); flex elbow (biceps)
C6	externally rotate (supinate) the arm
C6, C7	Extend elbow and wrist (triceps and wrist extensors); pronate wrist
C7, C8	Flex wrist; supply small muscles of the hand
T1–T6	Intercostals and trunk above the waist
T7–L1	Abdominal muscles
L1–L4	Flex hip joint
L2, L3, L4	Adduct thigh; Extend leg at the knee (quadriceps femoris)
L4, L5, S1	abduct thigh; Flex leg at the knee (hamstrings); Dorsiflex foot (tibialis anterior); Extend toes
L5, S1, S2	Extend leg at the hip (gluteus maximus); flex foot and flex toes

The corticospinal tract serves as the motor pathway for upper motor neuronal signals coming from the cerebral cortex and from primitive brainstem motor nuclei. 

Cortical upper motor neurons originate from Brodmann areas 1, 2, 3, 4, and 6 and then descend in the posterior limb of the internal capsule, through the crus cerebri, down through the pons, and to the medullary pyramids, where about 90% of the axons cross to the contralateral side at the decussation of the pyramids. They then descend as the lateral corticospinal tract. These axons synapse with lower motor neurons in the ventral horns of all levels of the spinal cord. The remaining 10% of axons descend on the ipsilateral side as the ventral corticospinal tract. These axons also synapse with lower motor neurons in the ventral horns. Most of them will cross to the contralateral side of the cord (via the anterior white commissure) right before synapsing. 

The midbrain nuclei include four motor tracts that send upper motor neuronal axons down the spinal cord to lower motor neurons. These are the rubrospinal tract, the vestibulospinal tract, the tectospinal tract and the reticulospinal tract. The rubrospinal tract descends with the lateral corticospinal tract, and the remaining three descend with the anterior corticospinal tract. 

The function of lower motor neurons can be divided into two different groups: the lateral corticospinal tract and the anterior cortical spinal tract. The lateral tract contains upper motor neuronal axons which synapse on dorsal lateral (DL) lower motor neurons. The DL neurons are involved in distal limb control. Therefore, these DL neurons are found specifically only in the cervical and lumbosacral enlargements within the spinal cord. There is no decussation in the lateral corticospinal tract after the decussation at the medullary pyramids.

The anterior corticospinal tract descends ipsilaterally in the anterior column, where the axons emerge and either synapse on lower ventromedial (VM) motor neurons in the ventral horn ipsilaterally or descussate at the anterior white commissure where they synapse on VM lower motor neurons contralaterally . The tectospinal, vestibulospinal and reticulospinal descend ipsilaterally in the anterior column but do not synapse across the anterior white commissure. Rather, they only synapse on VM lower motor neurons ipsilaterally. The VM lower motor neurons control the large, postural muscles of the axial skeleton. These lower motor neurons, unlike those of the DL, are located in the ventral horn all the way throughout the spinal cord.

Spinocerebellar tracts

Proprioceptive information in the body travels up the spinal cord via three tracks. Below L2, the proprioceptive information travels up the spinal cord in the ventral spinocerebellar tract. Also known as the anterior spinocerebellar tract, sensory receptors take in the information and travel into the spinal cord. The cell bodies of these primary neurons are located in the dorsal root ganglia. In the spinal cord, the axons synapse and the secondary neuronal axons decussates and then travel up to the superior cerebellar peduncle where they decussate again. From here, the information is brought to deep nuclei of the cerebellum including the fastigial and interposed nuclei. 

From the levels of L2 to T1, proprioceptive information enters the spinal cord and ascends ipsilaterally, where it synapses in Clarke's nucleus. The secondary neuronal axons continue to ascend ipsilaterally and then pass into the cerebellum via the inferior cerebellar peduncle. This tract is known as the dorsal spinocerebellar tract. 

From above T1, proprioceptive primary axons enter the spinal cord and ascend ipsilaterally until reaching the accessory cuneate nucleus, where they synapse. The secondary axons pass into the cerebellum via the inferior cerebellar peduncle where again, these axons synapse on cerebellar deep nuclei. This tract is known as the cuneocerebellar tract. 

Motor information travels from the brain down the spinal cord via descending spinal cord tracts. Descending tracts involve two neurons: the upper motor neuron (UMN) and lower motor neuron (LMN). A nerve signal travels down the upper motor neuron until it synapses with the lower motor neuron in the spinal cord. Then, the lower motor neuron conducts the nerve signal to the spinal root where efferent nerve fibers carry the motor signal toward the target muscle. The descending tracts are composed of white matter. There are several descending tracts serving different functions. The corticospinal tracts (lateral and anterior) are responsible for coordinated limb movements.

Clinical significance

A congenital disorder is diastematomyelia in which part of the spinal cord is split usually at the level of the upper lumbar vertebrae. Sometimes the split can be along the length of the spinal cord.

Injury

Spinal cord injuries can be caused by trauma to the spinal column (stretching, bruising, applying pressure, severing, laceration, etc.). The vertebral bones or intervertebral disks can shatter, causing the spinal cord to be punctured by a sharp fragment of bone. Usually, victims of spinal cord injuries will suffer loss of feeling in certain parts of their body. In milder cases, a victim might only suffer loss of hand or foot function. More severe injuries may result in paraplegia, tetraplegia (also known as quadriplegia), or full body paralysis below the site of injury to the spinal cord. 

Damage to upper motor neuron axons in the spinal cord results in a characteristic pattern of ipsilateral deficits. These include hyperreflexia, hypertonia and muscle weakness. Lower motor neuronal damage results in its own characteristic pattern of deficits. Rather than an entire side of deficits, there is a pattern relating to the myotome affected by the damage. Additionally, lower motor neurons are characterized by muscle weakness, hypotonia, hyporeflexia and muscle atrophy. 

Spinal shock and neurogenic shock can occur from a spinal injury. Spinal shock is usually temporary, lasting only for 24–48 hours, and is a temporary absence of sensory and motor functions. Neurogenic shock lasts for weeks and can lead to a loss of muscle tone due to disuse of the muscles below the injured site. 

The two areas of the spinal cord most commonly injured are the cervical spine (C1–C7) and the lumbar spine (L1–L5). (The notation C1, C7, L1, L5 refer to the location of a specific vertebra in either the cervical, thoracic, or lumbar region of the spine.) Spinal cord injury can also be non-traumatic and caused by disease (transverse myelitis, polio, spina bifida, Friedreich's ataxia, spinal cord tumor, spinal stenosis etc.)

In the U.S., 10,000–12,000 people become paralyzed annually as a result of various injuries to the spinal cord.

Treatment

Real or suspected spinal cord injuries need immediate immobilisation including that of the head. Scans will be needed to assess the injury. A steroid, methylprednisolone, can be of help as can physical therapy and possibly antioxidants. Treatments need to focus on limiting post-injury cell death, promoting cell regeneration, and replacing lost cells. Regeneration is facilitated by maintaining electric transmission in neural elements.

Lumbar puncture

The spinal cord ends at the level of vertebrae L1–L2, while the subarachnoid space —the compartment that contains cerebrospinal fluid— extends down to the lower border of S2. Lumbar punctures in adults are usually performed between L3–L5 (cauda equina level) in order to avoid damage to the spinal cord. In the fetus, the spinal cord extends the full length of the spine and regresses as the body grows.

Tumours

Spinal tumours can occur in the spinal cord and these can be either inside (intradural) or outside (extradural) the dura mater.