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.  [23]  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:  [24]

* 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  .  [25]  However, more subdivisions of loops have been proposed, up to 20,000.  [26]

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
 .  [27]  The direct
pathway has been proposed to facilitate motor actions, timing of motor
actions, gating of  working memory  ,
and motor responses to specific stimuli.  [26]

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
 .  [27]  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.  [26]

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_ .  [28]  [29]  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.  [26]

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.  [26]

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.