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 oralis. 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 pallidum 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 consists 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 state, 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 main article: basal ganglia disease 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, conditions, and symptoms 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 epilepsy fahr's disease foreign accent syndrome (fas) huntington's disease kernicterus lesch–nyhan syndrome major depressive disorder obsessive-compulsive disorder other anxiety disorders pandas (disorder) parkinson's disease restless legs syndrome schizophrenia spasmodic dysphonia stuttering sydenham's chorea tardive dyskinesia, caused by chronic antipsychotic treatment tourette's syndrome 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