basal ganglia basal ganglia the basal ganglia (bg), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. in humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an external and internal region, and in the division of the striatum. the basal ganglia are situated at the base of the forebrain and top of the midbrain. 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, conditional learning, eye movements, cognition, and emotion. this article is about the basal ganglia of vertebrates. for detailed information on the circuitries specific to primates, see primate basal ganglia. basal gangliabasal ganglia (red) and related structures (blue) shown within the brainbasal ganglia from anterior view of braindetailspart ofcerebrumidentifierslatinnuclei basalesacronym(s)bgmeshd001479neuronames224, 2677neurolex idbirnlex_826ta98a14.1.09.501ta25559fma84013anatomical terms of neuroanatomy the main components of the basal ganglia – as defined functionally – are the striatum, consisting of both the dorsal striatum (caudate nucleus and putamen) and the ventral striatum (nucleus accumbens and olfactory tubercle), the globus pallidus, the ventral pallidum, the substantia nigra, and the 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 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 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. 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 (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 main article: 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 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 (i.e. constantly releasing neurotransmitter unless inhibited) 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 main article: 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 main article: 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 further information: cortico-basal ganglia-thalamo-cortical loop 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