Basal ganglia

The basal ganglia or basal nuclei are a group of subcortical nuclei found in the brains of vertebrates. Positioned at the base of the forebrain and the top of the midbrain, they have strong connections with the cerebral cortex, thalamus, brainstem and other brain areas. The basal ganglia are associated with a variety of functions, including regulating voluntary motor movements, procedural learning, habit formation, conditional learning, eye movements, cognition, and emotion.
The main functional components of the basal ganglia include the striatum, consisting of both the dorsal striatum and the ventral striatum, the globus pallidus, the ventral pallidum, the substantia nigra, and the subthalamic nucleus. Each of these components has complex internal anatomical and neurochemical structures. The largest component, the striatum, receives input from various brain areas but only sends output to other components of the basal ganglia. The globus pallidus 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 mainly receives input from the striatum and cerebral cortex and projects to the globus pallidus.
The basal ganglia are thought to play a key role in action selection, aiding in the choice of behaviors to execute. More specifically, they regulate motor and premotor cortical areas, facilitating smooth voluntary movements. 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. It has also been hypothesized that the basal ganglia are not only responsible for motor action selection, but also for the selection of more cognitive actions. Computational models of action selection in the basal ganglia incorporate this.
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, as well as cognitive deficits that are similar to those that result from damage to the prefrontal cortex. 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. 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 the development of the nervous system in humans, the central nervous system is often classified based on the original three primitive brain vesicles: 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 orientation. Later in development 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 : substantia nigra pars compacta , substantia nigra pars reticulata
Rhombencephalon	Metencephalon Myelencephalon	Pons and cerebellum Medulla

File:Basal-ganglia-coronal-sections-large.png|thumb|400px|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
Posterior: subthalamic nucleus, substantia nigra
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 : 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 in the brain than the striatum and pallidum.

Striatum

The striatum is a subcortical structure generally divided into the dorsal striatum and ventral striatum. The dorsal striatum is further divided into a dorsomedial and dorsolateral striatum.
The striatum is composed mostly of medium spiny neurons. These GABAergic neurons project to the external globus pallidus and internal 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, 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 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, the internal globus pallidus and the external globus pallidus. 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 with an increased rate of firing in the targets.

Substantia nigra

The substantia nigra is a midbrain gray matter portion of the basal ganglia that has two parts – the pars compacta and the pars reticulata. SNr often works in unison with GPi, and the SNr–GPi complex inhibits the thalamus. Substantia nigra pars compacta 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.