Editing Basal ganglia (section)

== 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 vesicle]]s: 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 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 eminence]]s.<ref>Marín & Rubenstein. (2001). A Long, Remarkable Journey: Tangential Migration in the Telencephalon. ''Nature Reviews Neuroscience, 2.''</ref> The following table demonstrates this developmental classification and traces it to the anatomic structures found in the basal ganglia.<ref name=a1 /><ref name=brs /><ref>{{cite web|url=http://biology.about.com/library/organs/brain/blprosenceph.htm|title=Divisions of the Brain| vauthors = Bailey R |publisher=about.com|access-date=2010-11-30| archive-url= https://web.archive.org/web/20101202223928/http://biology.about.com/library/organs/brain/blprosenceph.htm| archive-date= 2 December 2010 | url-status= live}}</ref> The structures relevant to the basal ganglia are shown in '''bold'''.

{| class="wikitable"
! scope="col" | Primary division of the [[neural tube]]
! scope="col" | Secondary subdivision 
! scope="col" | Final segments in a human adult
|-
! scope="row" | [[Prosencephalon]]
|
# [[Telencephalon]]
# [[Diencephalon]]
|
# On each side of the brain: the cerebral cortices, '''caudate''', '''putamen''', '''Globus pallidus''', '''ventral pallidum''' 
# Thalamus, subthalamus, epithalamus, hypothalamus, '''subthalamic nucleus'''
|-
! scope="row" | [[Mesencephalon]]
|
# Mesencephalon
|
# Mesencephalon (midbrain): '''substantia nigra pars compacta (SNc)''', '''substantia nigra pars reticulata (SNr)'''
|-
! scope="row" | [[Rhombencephalon]]
|
# [[Metencephalon]]
# [[Myelencephalon]]
|
# Pons and cerebellum
# Medulla
|-
|}
[[File:Anatomy of the Basal Ganglia.ogv|thumb|Video of relevant anatomy]]
[[File:Basal-ganglia-coronal-sections-large.png|thumb|400px|[[Anatomical terms of location|Coronal]] slices of human brain showing the basal ganglia.  White matter is shown in dark gray, gray matter is shown in light gray.<br />Anterior: [[striatum]], [[globus pallidus]] (GPe and GPi)<br />Posterior: [[subthalamic nucleus]] (STN), [[substantia nigra]] (SN)]]

The basal ganglia form a fundamental component of the [[cerebrum]].  In contrast to the [[cerebral cortex|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.<ref name="Hall">{{cite book| vauthors = Hall J |title=Guyton and Hall textbook of medical physiology|date=2011|publisher=Saunders/Elsevier|location=Philadelphia, Pa.|isbn=978-1-4160-4574-8|page=690|edition=12th}}</ref> 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 [[Anatomical terms of location#Superior and inferior|superior]] or [[Anatomical terms of location#Directional terms|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 [[Anatomical terms of location|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 ([[Posterior (anatomy)|posteriorly]]) in the brain than the striatum and pallidum.

===Striatum===
{{Main|Striatum}}
[[File:Anatomy of the basal ganglia.jpg|thumb|left|220px|Basal ganglia]]
The striatum is a subcortical structure generally divided into the [[dorsal striatum]] and [[ventral striatum]]. The dorsal striatum is further divided into a [[Dorsomedial striatum|dorsomedial]] and [[dorsolateral striatum]].<ref name="JoN2022">{{cite journal | vauthors = Turner KM, Svegborn A, Langguth M, McKenzie C, Robbins TW | title = Opposing Roles of the Dorsolateral and Dorsomedial Striatum in the Acquisition of Skilled Action Sequencing in Rats | journal = The Journal of Neuroscience | volume = 42 | issue = 10 | pages = 2039–2051 | date = March 2022 | pmid = 35086903 | pmc = 8916752 | doi = 10.1523/JNEUROSCI.1907-21.2022 }}</ref><ref>{{cite journal | vauthors = Voorn P, Vanderschuren LJ, Groenewegen HJ, Robbins TW, Pennartz CM | title = Putting a spin on the dorsal-ventral divide of the striatum | journal = Trends in Neurosciences | volume = 27 | issue = 8 | pages = 468–474 | date = August 2004 | pmid = 15271494 | doi = 10.1016/j.tins.2004.06.006 | s2cid = 36496683 | author5-link = Cyriel Pennartz }}</ref><ref>{{cite journal | vauthors = Burton AC, Nakamura K, Roesch MR | title = From ventral-medial to dorsal-lateral striatum: neural correlates of reward-guided decision-making | journal = Neurobiology of Learning and Memory | volume = 117 | pages = 51–59 | date = January 2015 | pmid = 24858182 | pmc = 4240773 | doi = 10.1016/j.nlm.2014.05.003 }}</ref>

The striatum is composed mostly of [[medium spiny neuron]]s.  These [[GABAergic|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 [[gaseous signaling molecules|neurotransmitter]]), tonically active (i.e. constantly releasing neurotransmitter unless inhibited) cholinergic interneurons, [[parvalbumin]]-expressing neurons and [[calretinin]]-expressing neurons.<ref>{{cite journal | vauthors = Lanciego JL, Luquin N, Obeso JA | title = Functional neuroanatomy of the basal ganglia | journal = Cold Spring Harbor Perspectives in Medicine | volume = 2 | issue = 12 | pages = a009621 | date = December 2012 | pmid = 23071379 | pmc = 3543080 | doi = 10.1101/cshperspect.a009621 }}</ref> 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.<ref>{{cite journal | vauthors = Threlfell S, Cragg SJ | title = Dopamine signaling in dorsal versus ventral striatum: the dynamic role of cholinergic interneurons | journal = Frontiers in Systems Neuroscience | volume = 5 | pages = 11 | date = 3 March 2011 | pmid = 21427783 | pmc = 3049415 | doi = 10.3389/fnsys.2011.00011 | doi-access = free }}</ref> The dorsal striatum is divided into the [[caudate nucleus|caudate]] and [[putamen]] by the [[internal capsule]] while the ventral striatum is composed of the [[nucleus accumbens]] and [[olfactory tubercle]].<ref>{{cite journal | vauthors = Ferré S, Lluís C, Justinova Z, Quiroz C, Orru M, Navarro G, Canela EI, Franco R, Goldberg SR | title = Adenosine-cannabinoid receptor interactions. Implications for striatal function | journal = British Journal of Pharmacology | volume = 160 | issue = 3 | pages = 443–453 | date = June 2010 | pmid = 20590556 | pmc = 2931547 | doi = 10.1111/j.1476-5381.2010.00723.x }}</ref><ref name="Haber">{{cite book| vauthors = Haber SN |title=Neuroanatomy of Reward: A View from the Ventral Striatum|url=https://www.ncbi.nlm.nih.gov/books/NBK92777/|publisher=CRC Press/Taylor & Francis|date=1 January 2011|pmid=22593898 |isbn=9781420067262|access-date=9 March 2017|archive-date=3 March 2021|archive-url=https://web.archive.org/web/20210303205023/https://www.ncbi.nlm.nih.gov/books/NBK92777/|url-status=live}}</ref> 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.<ref>{{cite journal | vauthors = Robinson JL, Laird AR, Glahn DC, Blangero J, Sanghera MK, Pessoa L, Fox PM, Uecker A, Friehs G, Young KA, Griffin JL, Lovallo WR, Fox PT | title = The functional connectivity of the human caudate: an application of meta-analytic connectivity modeling with behavioral filtering | journal = NeuroImage | volume = 60 | issue = 1 | pages = 117–129 | date = March 2012 | pmid = 22197743 | pmc = 3288226 | doi = 10.1016/j.neuroimage.2011.12.010 }}</ref> [[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, the [[internal globus pallidus]] (GPi) and the [[external globus pallidus]] (GPe).<ref name=a1 /> Both segments contain primarily GABAergic neurons, which therefore have inhibitory effects on their targets. The two segments participate in distinct [[neural circuit]]s. 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|Substantia nigra}}
[[File:Blausen 0076 BasalGanglia.png|thumb|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|Subthalamic nucleus}}
The subthalamic nucleus is a [[Diencephalon|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 of movement|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===
{{see|Cortico-basal ganglia-thalamo-cortical loop}}
[[File:basal-ganglia-classic.png|thumb|200px|right|Connectivity diagram showing excitatory [[glutamatergic]] pathways as {{color|red|red}}, inhibitory [[GABA]]ergic pathways as {{color|blue|blue}}, and modulatory [[dopaminergic]] pathways as {{color|magenta|magenta}}. (Abbreviations: GPe: globus pallidus external; GPi: globus pallidus internal; STN: subthalamic nucleus; SNc: substantia nigra pars compacta; SNr: substantia nigra pars reticulata)]]
[[File:Motor loop.png|thumb|Connectivity of the basal ganglia as revealed by [[Diffusion MRI|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.]]
[[File:The conditional routing model.jpg|thumb|left|260px|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 pathway|direct]] and [[indirect pathway]]s, their possible overlap and regulation.<ref>{{cite journal | vauthors = Calabresi P, Picconi B, Tozzi A, Ghiglieri V, Di Filippo M | title = Direct and indirect pathways of basal ganglia: a critical reappraisal | journal = Nature Neuroscience | volume = 17 | issue = 8 | pages = 1022–1030 | date = August 2014 | pmid = 25065439 | doi = 10.1038/nn.3743 | url = https://www.researchgate.net/publication/264314897 | access-date = 15 January 2017 | url-status = live | s2cid = 8983260 | archive-url = https://web.archive.org/web/20210530083923/https://www.researchgate.net/publication/264314897_Direct_and_Indirect_Pathways_of_Basal_Ganglia_A_Critical_Reappraisal | archive-date = 30 May 2021 }}</ref> The circuitry model has evolved since the first proposed model in the 1990s by [[Mahlon DeLong|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|globus pallidus externus]], allowing for the disinhibition of the [[globus pallidus|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.

While implemented as a gradient without exact borders (or septa within the nuclei), the basal ganglia circuitry has often been divided into five pathways: one limbic, two associative (prefrontal), one oculomotor, and one motor pathway.<ref>{{cite journal | vauthors = Alexander GE, DeLong MR, Strick PL | title = Parallel organization of functionally segregated circuits linking basal ganglia and cortex | journal = Annual Review of Neuroscience | volume = 9 | issue = 1 | pages = 357–381 | date = March 1986 | pmid = 3085570 | doi = 10.1146/annurev.ne.09.030186.002041 }}</ref>  The motor and oculomotor pathways are sometimes grouped into one motor pathway. Furthermore, a simplified scheme into three domains (motor, associative and limbic) has gained popularity.<ref>{{cite journal | vauthors = Rodriguez-Oroz MC, Jahanshahi M, Krack P, Litvan I, Macias R, Bezard E, Obeso JA | title = Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms | journal = The Lancet. Neurology | volume = 8 | issue = 12 | pages = 1128–1139 | date = December 2009 | pmid = 19909911 | doi = 10.1016/S1474-4422(09)70293-5 | url = https://archive-ouverte.unige.ch/unige:95918 }}</ref> The five general pathways are organized as follows:<ref>{{cite book | veditors = Squire L |display-editors=etal |title=Fundamental neuroscience|date=2013|publisher=Elsevier/Academic Press|location=Amsterdam|isbn=9780123858702|page=728|edition=4th}}</ref>

*The motor loop involving projections from the [[supplementary motor area]], arcuate premotor area, primary 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 [[insular cortex|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]].<ref name="DABG">{{cite journal | vauthors = Ikemoto S, Yang C, Tan A | title = Basal ganglia circuit loops, dopamine and motivation: A review and enquiry | journal = Behavioural Brain Research | volume = 290 | pages = 17–31 | date = September 2015 | pmid = 25907747 | pmc = 4447603 | doi = 10.1016/j.bbr.2015.04.018 }}</ref> However, more subdivisions of loops have been proposed, up to 20,000.<ref name="BG models">{{cite journal | vauthors = Schroll H, Hamker FH | title = Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy | journal = Frontiers in Systems Neuroscience | volume = 7 | pages = 122 | date = December 2013 | pmid = 24416002 | pmc = 3874581 | doi = 10.3389/fnsys.2013.00122 | doi-access = free }}</ref>

These circuits are known to interact (at least) on a cortico-cortical level (U-fibers), a cortico-striatal level (by diffuse projections from cortex to striatum), a thalamo-cortical level (by diffuse reciprocal connections across thalamus and cortex) and striato-nigral level.<ref>{{Cite book |title=Connectomic deep brain stimulation |date=2022 |publisher=Academic Press, an imprint of Elsevier |isbn=978-0-12-821861-7 | veditors = Horn A |location=London}}</ref> The latter interaction has been characterized in more detail by [[Suzanne Haber]] and colleagues in their 'spiral model', which postulated how the ventral striatum (limbic circuit) can influence the dorsal striatum (motor circuit) through the midbrain dopamine cells (ventral tegmental area, substantia nigra pars compacta and other regions). In this model, connections from the ventral tegmental area to the shell region of the nucleus accumbens form a “closed,” reciprocal loop. However, these projections also extend laterally to influence dopamine neurons that send signals to the rest of the ventral striatum, creating the initial segment of a feed-forward loop, or 'spiral'. This spiral continues through striato-nigro-striatal pathways, whereby the VS affects cognitive and motor striatal areas via midbrain dopamine neurons.<ref>{{cite journal | vauthors = Haber SN, Knutson B | title = The reward circuit: linking primate anatomy and human imaging | journal = Neuropsychopharmacology | volume = 35 | issue = 1 | pages = 4–26 | date = January 2010 | pmid = 19812543 | pmc = 3055449 | doi = 10.1038/npp.2009.129 }}</ref><ref>{{cite journal | vauthors = Haber SN, Fudge JL, McFarland NR | title = Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum | journal = The Journal of Neuroscience | volume = 20 | issue = 6 | pages = 2369–2382 | date = March 2000 | pmid = 10704511 | pmc = 6772499 | doi = 10.1523/JNEUROSCI.20-06-02369.2000 }}</ref>

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 neuron]]s (MSNs) that express [[dopamine receptor D1]], [[muscarinic acetylcholine receptor M4]], and [[adenosine receptor A1]].<ref name="receptors" /> The direct pathway has been proposed to facilitate motor actions, timing of motor actions, gating of [[working memory]], and motor responses to specific stimuli.<ref name="BG models" />

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]].<ref name="receptors">{{cite journal | vauthors = Silkis I | title = The cortico-basal ganglia-thalamocortical circuit with synaptic plasticity. II. Mechanism of synergistic modulation of thalamic activity via the direct and indirect pathways through the basal ganglia | journal = Bio Systems | volume = 59 | issue = 1 | pages = 7–14 | date = January 2001 | pmid = 11226622 | doi = 10.1016/s0303-2647(00)00135-0 }}</ref> 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.<ref name="BG models"/>

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''.<ref>{{cite journal | vauthors = DeLong M, Wichmann T | title = Changing views of basal ganglia circuits and circuit disorders | journal = Clinical EEG and Neuroscience | volume = 41 | issue = 2 | pages = 61–67 | date = April 2010 | pmid = 20521487 | pmc = 4305332 | doi = 10.1177/155005941004100204 }}</ref><ref>{{cite journal | vauthors = DeLong M, Wichmann T | title = Update on models of basal ganglia function and dysfunction | journal = Parkinsonism & Related Disorders | volume = 15 | issue = 3 | pages = S237–S240 | date = December 2009 | pmid = 20082999 | pmc = 4275124 | doi = 10.1016/S1353-8020(09)70822-3 }}</ref> 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.<ref name="BG models"/>

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.<ref name="BG models"/>

[[File:Basal ganglia circuits.svg|thumb |Diagram shows two coronal slices that have been superimposed to include the involved basal ganglia structures. {{color|green|Green arrows}} (+) refer to excitatory [[glutamatergic]] pathways, {{color|red|red arrows}} (–) refer to inhibitory [[gamma-Aminobutyric acid|GABAergic]] pathways and {{color|turquoise|turquoise arrows}} refer to [[dopaminergic]] pathways that are excitatory on the direct pathway and inhibitory on the indirect pathway.]]

===Neurotransmitters===
The basal ganglia receive many afferent [[Glutamate (neurotransmitter)|glutamatergic]] inputs, with predominantly [[GABAergic]] efferent fibers, modulatory [[acetylcholine|cholinergic]] pathways, significant dopamine in the pathways originating in the [[ventral tegmental area]] and [[substantia nigra]], as well as various [[neuropeptide]]s.  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]].<ref>{{cite book| vauthors = Sian J, Youdim MB, Riederer P, Gerlach M |title=Biochemical Anatomy of the Basal Ganglia and Associated Neural Systems|year=1999|publisher=Lippincott-Raven |url=https://www.ncbi.nlm.nih.gov/books/NBK27905/|language=en|access-date=15 January 2017|archive-date=30 May 2021|archive-url=https://web.archive.org/web/20210530083923/https://www.ncbi.nlm.nih.gov/books/NBK27905/|url-status=live}}</ref>

===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.<ref>{{cite journal | vauthors = Postuma RB, Dagher A | title = Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications | journal = Cerebral Cortex | volume = 16 | issue = 10 | pages = 1508–1521 | date = October 2006 | pmid = 16373457 | doi = 10.1093/cercor/bhj088 | doi-access = free }}</ref>