striatum

File:Striatum Structural MRI.png. The striatum includes the caudate nucleus and the lentiform nucleus which includes the putamen and the globus pallidus |The striatum in red as seen on MRI. The striatum includes the caudate nucleus (top), and the lentiform nucleus (the putamen (right) and the globus pallidus (lower left))]]

The striatum is the largest structure of the basal ganglia. The striatum is divided into two subdivisions, a ventral striatum and a dorsal striatum, based upon function and connections. It is also divisible into a matrix and embedded striosomes.

The ventral striatum is composed of the nucleus accumbens and the olfactory tubercle.{{Cite journal |vauthors=Ubeda-Bañon I, Novejarque A, Mohedano-Moriano A, etal |title=Projections from the posterolateral olfactory amygdala to the ventral striatum: neural basis for reinforcing properties of chemical stimuli |journal=BMC Neurosci |volume=8 |pages=103 |year=2007 |pmid=18047654 |pmc=2216080 |doi=10.1186/1471-2202-8-103 |doi-access=free }} The nucleus accumbens is made up of the nucleus accumbens core and the nucleus accumbens shell, which differ by neural populations. The olfactory tubercle receives input from the olfactory bulb but has not been shown to play a role in processing smell. In non-primate species, the islands of Calleja are included.{{Cite web|title = Ventral striatum – NeuroLex|url = http://neurolex.org/wiki/Nlx_57107#tab=Basic|website = neurolex.org|access-date = 2015-12-12}} The ventral striatum is associated with the limbic system and has been implicated as a vital part of the circuitry for decision making and reward-related behavior.{{Cite web|title = Ventral Striatum Definition – Medical Dictionary|url = http://medicaldictionary.net/ventral-striatum.html|website = medicaldictionary.net|access-date = 2015-11-18}}{{Cite web|title = Ventral Striatum – Medical Definition|url = http://www.medilexicon.com/medicaldictionary.php?t=85559|website = www.medilexicon.com|access-date = 2015-11-18}}

The dorsal striatum is composed of the caudate nucleus and the putamen.

Primarily it mediates cognition and involves motor and executive function. The dorsal striatum can be further subdivided into the dorsomedial striatum, and the dorsolateral striatum. Both of these areas have different roles in the acquisition of learnt behaviour and skill formation.{{cite journal |last1=Turner |first1=Karly M. |last2=Svegborn |first2=Anna |last3=Langguth |first3=Mia |last4=McKenzie |first4=Colin |last5=Robbins |first5=Trevor W. |title=Opposing Roles of the Dorsolateral and Dorsomedial Striatum in the Acquisition of Skilled Action Sequencing in Rats |journal=The Journal of Neuroscience |date=9 March 2022 |volume=42 |issue=10 |pages=2039–2051 |doi=10.1523/JNEUROSCI.1907-21.2022|pmid=35086903 |pmc=8916752 }} The dorsomedial region receives projections from the frontal and the parietal cortices. The dorsolateral region receives projections from the sensorimotor cortex.{{cite journal |last1=Macpherson |first1=Tom |last2=Hikida |first2=Takatoshi |title=Role of basal ganglia neurocircuitry in the pathology of psychiatric disorders |journal=Psychiatry and Clinical Neurosciences |date=June 2019 |volume=73 |issue=6 |pages=289–301 |doi=10.1111/pcn.12830}}

Neurochemistry studies have used staining techniques on the striatum that have identified two distinct striatal compartments, the matrix, and the striosome (or patch). The matrix is seen to be rich in acetylcholinesterase, while the embedded striosomes are acetylcholinesterase-poor. The matrix forms the bulk of the striatum, and receives input from most areas of the cerebral cortex.{{cite book |last1=Squire |first1=Larry |title=Fundamental neuroscience |date=2013 |publisher=Elsevier Academic Press |location=Amsterdam Heidelberg |isbn=9780123858702 |page=658 |edition=4.}} Clusters of neurons in the matrix, called matrisomes receive a similar input. Their output goes to both regions of the globus pallidus and to the substantia nigra pars reticulata.

The striosomes receive input from the prefrontal cortex and give outputs to the substantia nigra pars compacta. There are more striosomes present in the dorsal striatum making up 10-15% of the striatal volume, than in the ventral striatum.{{Cite journal|pmid=27977131|year=2017|last1=Brimblecombe|first1=K. R.|title=The Striosome and Matrix Compartments of the Striatum: A Path through the Labyrinth from Neurochemistry toward Function|journal=ACS Chemical Neuroscience|volume=8|issue=2|pages=235–242|last2=Cragg|first2=S. J.|doi=10.1021/acschemneuro.6b00333|doi-access=free}}

File:Dendritic spines.jpgs on medium spiny neuron of striatum]]

Types of cells in the striatum include:

• Medium spiny neurons (MSNs), which are the principal neurons of the striatum. They are GABAergic and, thus, are classified as inhibitory neurons. Medium spiny projection neurons comprise 95% of the total neuronal population of the human striatum. Medium spiny neurons have two characteristic types: D1-type MSNs and D2-type MSNs. A subpopulation of MSNs contain both D1-type and D2-type receptors, with approximately 40% of striatal MSNs expressing both DRD1 and DRD2 mRNA.{{cite journal |last1=Nishi |first1=Akinori |last2=Kuroiwa |first2=Mahomi |last3=Shuto |first3=Takahide |title=Mechanisms for the Modulation of Dopamine D1 Receptor Signaling in Striatal Neurons |journal=Frontiers in Neuroanatomy |date=2011 |volume=5 |pages=43 |doi=10.3389/fnana.2011.00043 |pmid=21811441 |pmc=3140648 |doi-access=free }}
• Cholinergic interneurons release acetylcholine, which has a variety of important effects in the striatum. In humans, other primates, and rodents, these interneurons respond to salient environmental stimuli with stereotyped responses that are temporally aligned with the responses of dopaminergic neurons of the substantia nigra.{{cite journal |last1=Goldberg |first1=J.A. |last2=Reynolds |first2=J.N.J. |title=Spontaneous firing and evoked pauses in the tonically active cholinergic interneurons of the striatum |journal=Neuroscience |date=December 2011 |volume=198 |pages=27–43 |doi=10.1016/j.neuroscience.2011.08.067 |pmid=21925242 |s2cid=21908514 }}{{cite journal |last1=Morris |first1=Genela |last2=Arkadir |first2=David |last3=Nevet |first3=Alon |last4=Vaadia |first4=Eilon |last5=Bergman |first5=Hagai |title=Coincident but Distinct Messages of Midbrain Dopamine and Striatal Tonically Active Neurons |journal=Neuron |date=July 2004 |volume=43 |issue=1 |pages=133–143 |doi=10.1016/j.neuron.2004.06.012 |pmid=15233923 |doi-access=free }} The large aspiny cholinergic interneurons themselves are affected by dopamine through D5 dopamine receptors.{{cite journal |last1=Bergson |first1=C |last2=Mrzljak |first2=L |last3=Smiley |first3=JF |last4=Pappy |first4=M |last5=Levenson |first5=R |last6=Goldman-Rakic |first6=PS |title=Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain |journal=The Journal of Neuroscience |date=1 December 1995 |volume=15 |issue=12 |pages=7821–7836 |doi=10.1523/JNEUROSCI.15-12-07821.1995 |pmid=8613722 |pmc=6577925 }} Dopamine also directly controls communication between cholinergic interneurons.{{cite journal |last1=Raz |first1=Aeyal |title=Neuronal synchronization of tonically active neurons in the striatum of normal and parkinsonian primates |journal=Journal of Neurophysiology |date=1996 |volume=76 |issue=3 |pages=2083–2088 |doi=10.1152/jn.1996.76.3.2083 |pmid=8890317}}{{cite journal |last1=Dorst |first1=Matthijs |title=Polysynaptic inhibition between striatal cholinergic interneurons shapes their network activity patterns in a dopamine-dependent manner |journal=Nature Communications |date=2020 |volume=11 |issue=1 |page=5113 |doi=10.1038/s41467-020-18882-y |pmid=33037215 |pmc=7547109 |bibcode=2020NatCo..11.5113D }}
• There are many types of GABAergic interneurons. The best known are parvalbumin expressing interneurons, also known as fast-spiking interneurons, which participate in powerful feedforward inhibition of principal neurons.{{cite journal |last1=Koós |first1=Tibor |last2=Tepper |first2=James M. |title=Inhibitory control of neostriatal projection neurons by GABAergic interneurons |journal=Nature Neuroscience |date=May 1999 |volume=2 |issue=5 |pages=467–472 |doi=10.1038/8138 |pmid=10321252 |s2cid=16088859 }} Also, there are GABAergic interneurons that express tyrosine hydroxylase,{{cite journal |last1=Ibanez-Sandoval |first1=O. |last2=Tecuapetla |first2=F. |last3=Unal |first3=B. |last4=Shah |first4=F. |last5=Koos |first5=T. |last6=Tepper |first6=J. M. |title=Electrophysiological and Morphological Characteristics and Synaptic Connectivity of Tyrosine Hydroxylase-Expressing Neurons in Adult Mouse Striatum |journal=Journal of Neuroscience |date=19 May 2010 |volume=30 |issue=20 |pages=6999–7016 |doi=10.1523/JNEUROSCI.5996-09.2010 |pmid=20484642 |pmc=4447206 }} somatostatin, nitric oxide synthase and neuropeptide-y. Recently, two types of neuropeptide-y expressing GABAergic interneurons have been described in detail,{{cite journal |last1=Ibanez-Sandoval |first1=O. |last2=Tecuapetla |first2=F. |last3=Unal |first3=B. |last4=Shah |first4=F. |last5=Koos |first5=T. |last6=Tepper |first6=J. M. |title=A Novel Functionally Distinct Subtype of Striatal Neuropeptide Y Interneuron |journal=Journal of Neuroscience |date=16 November 2011 |volume=31 |issue=46 |pages=16757–16769 |doi=10.1523/JNEUROSCI.2628-11.2011 |pmid=22090502 |pmc=3236391 }} one of which translates synchronous activity of cholinergic interneurons into inhibition of principal neurons.{{cite journal |last1=English |first1=Daniel F |last2=Ibanez-Sandoval |first2=Osvaldo |last3=Stark |first3=Eran |last4=Tecuapetla |first4=Fatuel |last5=Buzsáki |first5=György |last6=Deisseroth |first6=Karl |last7=Tepper |first7=James M |last8=Koos |first8=Tibor |title=GABAergic circuits mediate the reinforcement-related signals of striatal cholinergic interneurons |journal=Nature Neuroscience |date=11 December 2011 |volume=15 |issue=1 |pages=123–130 |doi=10.1038/nn.2984 |pmid=22158514 |pmc=3245803 }} These neurons of the striatum are not distributed evenly.{{cite journal |last1=Tepper |first1=James M. |last2=Tecuapetla |first2=Fatuel |last3=Koós |first3=Tibor |last4=Ibáñez-Sandoval |first4=Osvaldo |title=Heterogeneity and Diversity of Striatal GABAergic Interneurons |journal=Frontiers in Neuroanatomy |date=2010 |volume=4 |pages=150 |doi=10.3389/fnana.2010.00150 |pmid=21228905 |pmc=3016690 |doi-access=free }}

There are two regions of neurogenesis in the brain – the subventricular zone (SVZ) in the lateral ventricles, and the dentate gyrus in the hippocampal formation. Neuroblasts that form in the lateral ventricle adjacent to the striatum, integrate in the striatum.{{cite journal|last1=Ernst|first1=Aurélie|last2=Alkass|first2=Kanar|last3=Bernard|first3=Samuel|last4=Salehpour|first4=Mehran|last5=Perl|first5=Shira|last6=Tisdale|first6=John|last7=Possnert|first7=Göran|last8=Druid|first8=Henrik|last9=Frisén|first9=Jonas|title=Neurogenesis in the Striatum of the Adult Human Brain|journal=Cell|date=February 2014|volume=156|issue=5|pages=1072–1083|doi=10.1016/j.cell.2014.01.044|pmid=24561062|doi-access=free}}{{cite journal|last1=Inta|first1=D|last2=Lang|first2=U E|last3=Borgwardt|first3=S|last4=Meyer-Lindenberg|first4=A|last5=Gass|first5=P|title=Adult neurogenesis in the human striatum: possible implications for psychiatric disorders|journal=Molecular Psychiatry|date=16 February 2016|volume=21|issue=4|pages=446–447|doi=10.1038/mp.2016.8|pmid=26878892|doi-access=free}} This has been noted in the human striatum following an ischemic stroke. Injury caused to the striatum stimulates the migration of neuroblasts from the SVZ, to the striatum, where they differentiate into adult neurons.{{cite journal|last1=Kernie|first1=SG|last2=Parent|first2=JM|title=Forebrain neurogenesis after focal Ischemic and traumatic brain injury.|journal=Neurobiology of Disease|date=February 2010|volume=37|issue=2|pages=267–74|pmid=19909815|doi=10.1016/j.nbd.2009.11.002|pmc=2864918}} The normal passage of SVZ neuroblasts is to the olfactory bulb but this traffic is diverted to the striatum after an ischemic stroke. However, few of the new developed neurons survive.{{cite journal|last1=Yamashita|first1=T|last2=Ninomiya|first2=M|last3=Hernández Acosta|first3=P|last4=García-Verdugo|first4=JM|last5=Sunabori|first5=T|last6=Sakaguchi|first6=M|last7=Adachi|first7=K|last8=Kojima|first8=T|last9=Hirota|first9=Y|last10=Kawase|first10=T|last11=Araki|first11=N|last12=Abe|first12=K|last13=Okano|first13=H|last14=Sawamoto|first14=K|title=Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum.|journal=The Journal of Neuroscience|date=14 June 2006|volume=26|issue=24|pages=6627–36|pmid=16775151|doi=10.1523/jneurosci.0149-06.2006|pmc=6674034|url=http://ousar.lib.okayama-u.ac.jp/files/public/1/11746/20160527190854209485/K003322.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://ousar.lib.okayama-u.ac.jp/files/public/1/11746/20160527190854209485/K003322.pdf |archive-date=2022-10-09 |url-status=live}}

File:Basalganglien.png]]

File:Basal ganglia circuits.svg pathways, {{color|red|red arrows}} refer to inhibitory GABAergic pathways and {{color|turquoise|turquoise arrows}} refer to dopaminergic pathways that are excitatory on the direct pathway and inhibitory on the indirect pathway.]]

The largest connection is from the cortex, in terms of cell axons. Many parts of the neocortex innervate the dorsal striatum. The cortical pyramidal neurons projecting to the striatum are located in layers II-VI, with the most dense projections come from layer V.{{cite journal |last1=Rosell |first1=Antonio |last2=Giménez-Amaya |first2=José Manuel |title=Anatomical re-evaluation of the corticostriatal projections to the caudate nucleus: a retrograde labeling study in the cat |journal=Neuroscience Research |date=September 1999 |volume=34 |issue=4 |pages=257–269 |doi=10.1016/S0168-0102(99)00060-7 |pmid=10576548 |s2cid=31392396 }} They end mainly on the dendritic spines of the spiny neurons. They are glutamatergic, exciting striatal neurons.

The striatum is seen as having its own internal microcircuitry.{{cite journal |last1=Stocco |first1=Andrea |last2=Lebiere |first2=Christian |last3=Anderson |first3=John R. |title=Conditional Routing of Information to the Cortex: A Model of the Basal Ganglia's Role in Cognitive Coordination |journal=Psychological Review |volume=117 |issue=2 |pages=541–74 |year=2010 |pmid=20438237 |doi=10.1037/a0019077 |pmc=3064519}} The ventral striatum receives direct input from multiple regions in the cerebral cortex and limbic structures such as the amygdala, thalamus, and hippocampus, as well as the entorhinal cortex and the inferior temporal gyrus.{{Cite web|title = Ventral striatum – NeuroLex|url = http://neurolex.org/wiki/Nlx_57107#tab=Factbox|website = neurolex.org|access-date = 2015-12-12}} Its primary input is to the basal ganglia system. Additionally, the mesolimbic pathway projects from the ventral tegmental area to the nucleus accumbens of the ventral striatum.{{Cite web|title = Icahn School of Medicine {{!}} Neuroscience Department {{!}} Nestler Lab {{!}} Brain Reward Pathways|url = http://neuroscience.mssm.edu/nestler/brainRewardpathways.html|website = neuroscience.mssm.edu|access-date = 2015-12-12|archive-date = 5 June 2019|archive-url = https://web.archive.org/web/20190605073910/https://neuroscience.mssm.edu/nestler/brainRewardpathways.html|url-status = dead}}

Another well-known afferent is the nigrostriatal connection arising from the neurons of the substantia nigra pars compacta. While cortical axons synapse mainly on spine heads of spiny neurons, nigral axons synapse mainly on spine shafts.

In primates, the thalamostriatal afferent comes from the central median-parafascicular complex of the thalamus (see primate basal ganglia system). This afferent is glutamatergic. The participation of truly intralaminar neurons is much more limited.

The striatum also receives afferents from other elements of the basal ganglia such as the subthalamic nucleus (glutamatergic) or the external globus pallidus (GABAergic).

{{further|Medium spiny neuron}}

The primary outputs of the ventral striatum project to the ventral pallidum, then the medial dorsal nucleus of the thalamus, which is part of the frontostriatal circuit. Additionally, the ventral striatum projects to the globus pallidus, and substantia nigra pars reticulata. Some of its other outputs include projections to the extended amygdala, lateral hypothalamus, and pedunculopontine nucleus.{{cite journal |last1=Robbins |first1=Trevor W. |last2=Everitt |first2=Barry J. |title=Functions of dopamine in the dorsal and ventral striatum |journal=Seminars in Neuroscience |date=April 1992 |volume=4 |issue=2 |pages=119–127 |doi=10.1016/1044-5765(92)90010-Y }}

Striatal outputs from both the dorsal and ventral components are primarily composed of medium spiny neurons (MSNs), a type of projection neuron, which have two primary phenotypes: "indirect" MSNs that express D2-like receptors and "direct" MSNs that express D1-like receptors.{{cite journal |vauthors=Yager LM, Garcia AF, Wunsch AM, Ferguson SM | title = The ins and outs of the striatum: Role in drug addiction | journal = Neuroscience | volume = 301 | pages = 529–541 | date = August 2015 | pmid = 26116518 | doi = 10.1016/j.neuroscience.2015.06.033 | quote = [The striatum] receives dopaminergic inputs from the ventral tegmental area (VTA) and the substantia nigra (SNr) and glutamatergic inputs from several areas, including the cortex, hippocampus, amygdala, and thalamus (Swanson, 1982; Phillipson and Griffiths, 1985; Finch, 1996; Groenewegen et al., 1999; Britt et al., 2012). These glutamatergic inputs make contact on the heads of dendritic spines of the striatal GABAergic medium spiny projection neurons (MSNs) whereas dopaminergic inputs synapse onto the spine neck, allowing for an important and complex interaction between these two inputs in modulation of MSN activity ... It should also be noted that there is a small population of neurons in the NAc that coexpress both D1 and D2 receptors, though this is largely restricted to the NAc shell (Bertran- Gonzalez et al., 2008). ... Neurons in the NAc core and NAc shell subdivisions also differ functionally. The NAc core is involved in the processing of conditioned stimuli whereas the NAc shell is more important in the processing of unconditioned stimuli; Classically, these two striatal MSN populations are thought to have opposing effects on basal ganglia output. Activation of the dMSNs causes a net excitation of the thalamus resulting in a positive cortical feedback loop; thereby acting as a ‘go’ signal to initiate behavior. Activation of the iMSNs, however, causes a net inhibition of thalamic activity resulting in a negative cortical feedback loop and therefore serves as a ‘brake’ to inhibit behavior ... there is also mounting evidence that iMSNs play a role in motivation and addiction (Lobo and Nestler, 2011; Grueter et al., 2013). ... Together these data suggest that iMSNs normally act to restrain drug-taking behavior and recruitment of these neurons may in fact be protective against the development of compulsive drug use. | pmc=4523218}}{{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 = Br. J. Pharmacol. | volume = 160 | issue = 3 | pages = 443–453 | date = June 2010 | pmid = 20590556 | pmc = 2931547 | doi = 10.1111/j.1476-5381.2010.00723.x | quote = Two classes of MSNs, which are homogeneously distributed in the striatum, can be differentiated by their output connectivity and their expression of dopamine and adenosine receptors and neuropeptides. In the dorsal striatum (mostly represented by the nucleus caudate-putamen), enkephalinergic MSNs connect the striatum with the external globus pallidus and express the peptide enkephalin and a high density of dopamine D2 and adenosine A2A receptors (they also express adenosine A1 receptors), while dynorphinergic MSNs connect the striatum with the substantia nigra (pars compacta and reticulata) and the entopeduncular nucleus (internal globus pallidus) and express the peptides dynorphin and substance P and dopamine D1 and adenosine A1 but not A2A receptors ... These two different phenotypes of MSN are also present in the ventral striatum (mostly represented by the nucleus accumbens and the olfactory tubercle). However, although they are phenotypically equal to their dorsal counterparts, they have some differences in terms of connectivity. First, not only enkephalinergic but also dynorphinergic MSNs project to the ventral counterpart of the external globus pallidus, the ventral pallidum, which, in fact, has characteristics of both the external and internal globus pallidus in its afferent and efferent connectivity. In addition to the ventral pallidum, the internal globus pallidus and the substantia nigra-VTA, the ventral striatum sends projections to the extended amygdala, the lateral hypothalamus and the pedunculopontine tegmental nucleus. ... It is also important to mention that a small percentage of MSNs have a mixed phenotype and express both D1 and D2 receptors (Surmeier et al., 1996).}}

The main nucleus of the basal ganglia is the striatum which projects directly to the globus pallidus via a pathway of striatopallidal fibers.{{Cite journal|pmid=28154527|pmc=5243825|year=2016|last1=Pujol|first1=S.|title=In vivo Exploration of the Connectivity between the Subthalamic Nucleus and the Globus Pallidus in the Human Brain Using Multi-Fiber Tractography|journal=Frontiers in Neuroanatomy|volume=10|pages=119|last2=Cabeen|first2=R.|last3=Sébille|first3=S. B.|last4=Yelnik|first4=J.|last5=François|first5=C.|last6=Fernandez Vidal|first6=S.|last7=Karachi|first7=C.|last8=Zhao|first8=Y.|last9=Cosgrove|first9=G. R.|last10=Jannin|first10=P.|last11=Kikinis|first11=R.|last12=Bardinet|first12=E.|doi=10.3389/fnana.2016.00119|doi-access=free}} The striato-pallidal pathway has a whitish appearance due to the myelinated fibers. This projection comprises successively the external globus pallidus (GPe), the internal globus pallidus (GPi), the pars compacta of the substantia nigra (SNc), and the pars reticulata of substantia nigra (SNr). The neurons of this projection are inhibited by GABAergic synapses from the dorsal striatum. Among these targets, the GPe does not send axons outside the system. Others send axons to the superior colliculus. Two others comprise the output to the thalamus, forming two separate channels: one through the internal segment of the globus pallidus to the ventral oralis nuclei of the thalamus and from there to the cortical supplementary motor area and another through the substantia nigra to the ventral anterior nuclei of the thalamus and from there to the frontal cortex and the occulomotor cortex.

Deep penetrating striate arteries supply blood to the striatum. These arteries include the recurrent artery of Heubner arising from the anterior cerebral artery, and the lenticulostriate arteries arising from the middle cerebral artery.{{cite book |last1=Purves |first1=Dale |title=Neuroscience |date=2012 |location=Sunderland, Mass. |isbn=9780878936953 |page=739 |edition=5th}}

The ventral striatum, and the nucleus accumbens in particular, primarily mediates reward, cognition, reinforcement, and motivational salience. By contrast, the dorsal striatum primarily mediates cognition involving motor function, certain executive functions (e.g., inhibitory control and impulsivity), and stimulus-response learning.{{cite journal |doi=10.1111/nyas.13961 |title=The role of the dorsal striatum in choice impulsivity |year=2019 |last1=Kim |first1=BaekSun |last2=Im |first2=Heh-In |journal=Annals of the New York Academy of Sciences |volume=1451 |issue=1 |pages=92–111 |pmid=30277562|bibcode=2019NYASA1451...92K |s2cid=52897511 }} There is a small degree of overlap, as the dorsal striatum is also a component of the reward system that, along with the nucleus accumbens core, mediates the encoding of new motor programs associated with future reward acquisition (e.g., the conditioned motor response to a reward cue).{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 978-0-07-148127-4 | pages = 147–148, 321, 367, 376 | edition = 2nd | quote= VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards. ...
Functional neuroimaging in humans demonstrates activation of the prefrontal cortex and caudate nucleus (part of the striatum) in tasks that demand inhibitory control of behavior. ...
The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. ...
The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc.}}

The striatum is also thought to play a role in an at least partially dissociable executive control network for language, applied to both verbal working memory and verbal attention. These models take the form of a frontal-striatal network for language processing.{{cite journal |last1=Jacquemot |first1=Charlotte |last2=Bachoud-Lévi |first2=Anne-Catherine |title=Striatum and language processing: Where do we stand? |journal=Cognition |date=August 2021 |volume=213 |pages=104785 |doi=10.1016/j.cognition.2021.104785 |pmid=34059317 }} While the striatum is often not included in models of language processing, as most models only include cortical regions, integrative models are becoming more popular in light of imaging studies, lesion studies on aphasic patients, and studies of language disorders concomitant with diseases known to affect the striatum like Parkinson's and Huntington's disease.{{cite journal |last1=Ullman |first1=Michael T. |last2=Corkin |first2=Suzanne |last3=Coppola |first3=Marie |last4=Hickok |first4=Gregory |last5=Growdon |first5=John H. |last6=Koroshetz |first6=Walter J. |last7=Pinker |first7=Steven |title=A Neural Dissociation within Language: Evidence that the Mental Dictionary Is Part of Declarative Memory, and that Grammatical Rules Are Processed by the Procedural System |journal=Journal of Cognitive Neuroscience |date=March 1997 |volume=9 |issue=2 |pages=266–276 |doi=10.1162/jocn.1997.9.2.266 |pmid=23962016 |url=http://nrs.harvard.edu/urn-3:HUL.InstRepos:3600798 }}

Metabotropic dopamine receptors are present both on spiny neurons and on cortical axon terminals. Second messenger cascades triggered by activation of these dopamine receptors can modulate pre- and postsynaptic function, both in the short term and in the long term.{{Cite journal | pmid = 11691979| year = 2001| last1 = Greengard| first1 = P| author1-link = Paul Greengard| title = The neurobiology of slow synaptic transmission| journal = Science| volume = 294| issue = 5544| pages = 1024–30| doi = 10.1126/science.294.5544.1024| bibcode = 2001Sci...294.1024G}}{{Cite journal | pmid = 24904339| pmc = 4033078| year = 2014| last1 = Cachope| first1 = R| title = Local control of striatal dopamine release| journal = Frontiers in Behavioral Neuroscience| volume = 8| pages = 188| last2 = Cheer| doi = 10.3389/fnbeh.2014.00188| doi-access = free}} In humans, the striatum is activated by stimuli associated with reward, but also by aversive, novel,{{cite web|url=https://www.ucl.ac.uk/news/2008/jun/adventure-its-all-mind-say-ucl-neuroscientists|title=Adventure - it's all in the mind, say UCL neuroscientists|last=UCL|date=25 June 2008|website=UCL News}} unexpected, or intense stimuli, and cues associated with such events.{{Cite journal | pmid = 24198347| pmc = 3818538| year = 2013| last1 = Volman| first1 = S. F.| title = New insights into the specificity and plasticity of reward and aversion encoding in the mesolimbic system| journal = Journal of Neuroscience| volume = 33| issue = 45| pages = 17569–76| last2 = Lammel| last3 = Margolis| last4 = Kim| last5 = Richard| last6 = Roitman| last7 = Lobo| doi = 10.1523/JNEUROSCI.3250-13.2013}} fMRI evidence suggests that the common property linking these stimuli, to which the striatum is reacting, is salience under the conditions of presentation.{{cite journal|last=LUNA|first=BEATRIZ|author2=SWEENEY, JOHN A. |title=The Emergence of Collaborative Brain Function: fMRI Studies of the Development of Response Inhibition|journal=Annals of the New York Academy of Sciences|date=1 June 2004|volume=1021|issue=1|pages=296–309|doi=10.1196/annals.1308.035|pmid=15251900|bibcode=2004NYASA1021..296L|s2cid=37404147}}{{cite web |url=http://www.pdn.cam.ac.uk/staff/schultz/ |title=Department of Physiology, Development and Neuroscience: About the Department |access-date=15 December 2007 |archive-date=11 April 2012 |archive-url=https://web.archive.org/web/20120411193109/http://www.pdn.cam.ac.uk/staff/schultz/ |url-status=dead }} A number of other brain areas and circuits are also related to reward, such as frontal areas. Functional maps of the striatum reveal interactions with widely distributed regions of the cerebral cortex important to a diverse range of functions.{{cite journal|vauthors=Choi EY, Yeo BT, Buckner RL |title=The organization of the human striatum estimated by intrinsic functional connectivity |journal=Journal of Neurophysiology |date = 2012 |volume = 108 |issue=8 |pages=2242–2263 |doi= 10.1152/jn.00270.2012 |pmid= 22832566 |pmc=3545026}}

The interplay between the striatum and the prefrontal cortex is relevant for behavior, particularly adolescent development as proposed by the dual systems model.{{Cite journal|last=Steinberg|first=Laurence|date=April 2010|title=A dual systems model of adolescent risk-taking|journal=Developmental Psychobiology|volume=52|issue=3|pages=216–224|doi=10.1002/dev.20445|issn=1098-2302|pmid=20213754|doi-access=free}}

Parkinson's disease results in loss of dopaminergic innervation to the dorsal striatum (and other basal ganglia) and a cascade of consequences. Atrophy of the striatum is also involved in Huntington's disease, and movement disorders such as chorea, choreoathetosis, and dyskinesias.{{cite journal |author=Walker FO |title=Huntington's disease |journal=Lancet |volume=369 |issue=9557 |pages=218–28 |date=January 2007 |pmid=17240289 |doi=10.1016/S0140-6736(07)60111-1 |s2cid=46151626 }} These have also been described as circuit disorders of the basal ganglia.{{Cite journal|pmid=17210805|year=2007|last1=Delong|first1=M. R.|title=Circuits and circuit disorders of the basal ganglia|journal=Archives of Neurology|volume=64|issue=1|pages=20–4|last2=Wichmann|first2=T.|doi=10.1001/archneur.64.1.20|doi-access=|s2cid=9606341 }}

File:Overview of reward structures in the human brain.jpg

Addiction, a disorder of the brain's reward system, arises through the overexpression of DeltaFosB (ΔFosB), a transcription factor, in the D1-type medium spiny neurons of the ventral striatum. ΔFosB is an inducible gene which is increasingly expressed in the nucleus accumbens as a result of repeatedly using an addictive drug or overexposure to other addictive stimuli.{{cite journal | author = Nestler EJ | title = Cellular basis of memory for addiction | journal = Dialogues Clin. Neurosci. | volume = 15 | issue = 4 | pages = 431–443 |date=December 2013 | doi = 10.31887/DCNS.2013.15.4/enestler | pmid = 24459410 | pmc = 3898681 }}{{cite journal | vauthors = Olsen CM | title = Natural rewards, neuroplasticity, and non-drug addictions | journal = Neuropharmacology | volume = 61 | issue = 7 | pages = 1109–22 | date = Dec 2011 | pmid = 21459101 | pmc = 3139704 | doi = 10.1016/j.neuropharm.2011.03.010 }}
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139704/table/T1/?report=objectonly Table 1]

The mesolimbic hypothesis of schizophrenia has long emphasized the role of hyperdopaminergia in the mesolimbic pathway, which extends from the ventral tegmental area to the ventral striatum.{{cite journal |last1= Simpson |first1=E-H |last2= Kellendonk |first2=C |last3= Kandel |first3=E |title=A Possible Role for the Striatum in the Pathogenesis of the Cognitive Symptoms of Schizophrenia|journal=Neuron |date=11 March 2010 |volume=65 |issue=5 |pages= 585–596 | doi=10.1016/j.neuron.2010.02.014 |pmid= 20223196}} Abnormally elevated dopaminergic transmission in this pathway has been associated with the emergence of positive symptoms, such as hallucinations and delusions.{{cite journal |last1= Conn |first1=K-A |last2= Burne |first2=T-H-J |last3= Kesby |first3=J-P |title= Subcortical Dopamine and Cognition in Schizophrenia: Looking Beyond Psychosis in Preclinical Models |journal= Frontiers in Neuroscience |date=3 June 2020 |volume=14 | doi=10.3389/fnins.2020.00542 |doi-access=free |pmid= 32655348}} Most antipsychotic treatments exert their effects by reducing dopamine binding to receptors in this region.{{cite journal |last1= Kaar |first1=S-J |last2= Natesan |first2=S |last3= McCutcheon |first3=R |last4= Howes |first4=O-D|title= Antipsychotics: Mechanisms underlying clinical response and side-effects and novel treatment approaches based on pathophysiology|journal=Neuropharmacology |date=1 August 2020 |volume= 172 | doi=10.1016/j.neuropharm.2019.107704 |pmid= 20223196}}

More recent evidence, however, suggests that the pathway from the substantia nigra dorsal striatum may also play a significant role in the pathophysiology of schizophrenia.{{cite journal |last1= McCutcheon |first1=R |last2= Beck |first2=K |last3= Jauhar |first3=S |last4= Howes |first4=O-D |title= Defining the Locus of Dopaminergic Dysfunction in Schizophrenia: A Meta-analysis and Test of the Mesolimbic Hypothesis |journal=Schizophrenia Bulletin |date=17 October 2018 |volume=44 |issue=6 |pages= 1301–1311 | doi=10.1093/schbul/sbx180 |pmid= 29301039}} This has led to the development of the mesostriatal hypothesis, which expands the focus beyond the ventral striatum to include dopaminergic dysfunction in the dorsal components of the striatum and could help accounting for the negative and cognitive symptoms.{{cite journal |last1= Grimaldi |first1=D-A |last2= Patane' |first2=A |last3= Cattarinussi |first3=G |last4= Sambataro |first4=F |title= Functional connectivity of the striatum in psychosis: Meta-analysis of functional magnetic resonance imaging studies and replication on an independent sample |journal=Neuroscience & Biobehavioral Reviews |date=2 May 2025 |volume=174 |doi=10.1016/j.neubiorev.2025.106179 |pmid= 40288705}}

An association has been observed between striatal expression of variants of the PDE10A gene and some bipolar I disorder patients. Variants of other genes, DISC1 and GNAS, have been associated with bipolar II disorder.{{cite journal |last1=McDonald |first1=M-L |last2=MacMullen |first2=C |last3=Liu |first3=D J |last4=Leal |first4=S M |last5=Davis |first5=R L |title=Genetic association of cyclic AMP signaling genes with bipolar disorder |journal=Translational Psychiatry |date=2 October 2012 |volume=2 |issue=10 |pages=e169 |doi=10.1038/tp.2012.92 |pmid=23032945 |pmc=3565822 }}

Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and poor understanding of social systems. This inflexible behavior originates in defects in the pre-frontal cortex as well as the striatal circuits.{{cite journal |last1=Fineberg |first1=Naomi A |last2=Potenza |first2=Marc N |last3=Chamberlain |first3=Samuel R |last4=Berlin |first4=Heather A |last5=Menzies |first5=Lara |last6=Bechara |first6=Antoine |last7=Sahakian |first7=Barbara J |last8=Robbins |first8=Trevor W |last9=Bullmore |first9=Edward T |last10=Hollander |first10=Eric |title=Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review |journal=Neuropsychopharmacology |date=25 November 2009 |volume=35 |issue=3 |pages=591–604 |doi=10.1038/npp.2009.185 |pmc=3055606 |pmid=19940844 }} The defects in the striatum seem to specifically contribute to the motor, social and communication impairments seen in ASD patients. In mice which have an ASD-like phenotype induced via the overexpression of the eukaryotic initiation of translation factor 4E, it has been shown that these defects seem to stem from the reduced ability to store and process information in the striatum, which leads to the difficulty seen in forming new motor patterns, as well as disengaging from existing ones.{{cite journal |last1=Santini |first1=Emanuela |last2=Huynh |first2=Thu N. |last3=MacAskill |first3=Andrew F. |last4=Carter |first4=Adam G. |last5=Pierre |first5=Philippe |last6=Ruggero |first6=Davide |last7=Kaphzan |first7=Hanoch |last8=Klann |first8=Eric |title=Exaggerated translation causes synaptic and behavioural aberrations associated with autism |journal=Nature |date=23 December 2012 |volume=493 |issue=7432 |pages=411–415 |doi=10.1038/nature11782 |pmid=23263185 |pmc=3548017 |bibcode=2013Natur.493..411S }}

Dysfunction in the ventral striatum can lead to a variety of disorders, most notably depression and obsessive-compulsive disorder. Because of its involvement in reward pathways, the ventral striatum has also been implicated in playing a critical role in addiction. It has been well established that the ventral striatum is strongly involved in mediating the reinforcing effects of drugs, especially stimulants, through dopaminergic stimulation.{{cite journal |last1=Everitt |first1=Barry J. |last2=Robbins |first2=Trevor W. |title=From the ventral to the dorsal striatum: Devolving views of their roles in drug addiction |journal=Neuroscience & Biobehavioral Reviews |date=November 2013 |volume=37 |issue=9 |pages=1946–1954 |doi=10.1016/j.neubiorev.2013.02.010 |pmid=23438892 |doi-access=free }}

Lesions to the striatum have been associated with deficits in speech production and comprehension. While striatal damage can impact all levels of language, damage can broadly be characterized as affecting the ability to manipulate linguistic units and rules, resulting in the promotion of default linguistic forms in conflicting situations in which selection, inhibition, and monitoring load is increased.{{Cite journal |last=Fedorenko |first=Evelina |date=2014 |title=The role of domain-general cognitive control in language comprehension |journal=Frontiers in Psychology |volume=5 |page=335 |doi=10.3389/fpsyg.2014.00335 |doi-access=free|pmid=24803909 |pmc=4009428 |issn=1664-1078}} Two subregions of the striatum have been shown to be particularly important in language: the caudate nucleus and left putamen. Lesions localized to the caudate nucleus, as well as direct electrical stimulation, can result in lexical paraphasias and perservations (continuations of an utterance after the stimulus has ceased), which is associated with inhibited executive control, in the sense that executive control allows for the selection of the best choice among competing alternatives).{{Cite journal |last1=Kreisler |first1=A. |last2=Godefroy |first2=O. |last3=Delmaire |first3=C. |last4=Debachy |first4=B. |last5=Leclercq |first5=M. |last6=Pruvo |first6=J.-P. |last7=Leys |first7=D. |date=2000-03-14 |title=The anatomy of aphasia revisited |url=https://n.neurology.org/content/54/5/1117 |journal=Neurology |language=en |volume=54 |issue=5 |pages=1117–1123 |doi=10.1212/WNL.54.5.1117 |issn=0028-3878 |pmid=10720284|s2cid=21847976 |url-access=subscription }} Stimulation of the putamen results in the inhibition of articulatory sequences and the inability to initiate motor speech commands.{{Cite journal |last1=Robles |first1=S. Gil |last2=Gatignol |first2=P. |last3=Capelle |first3=L. |last4=Mitchell |first4=M.-C. |last5=Duffau |first5=H. |date=2005-07-01 |title=The role of dominant striatum in language: a study using intraoperative electrical stimulations |journal=Journal of Neurology, Neurosurgery & Psychiatry |language=en |volume=76 |issue=7 |pages=940–946 |doi=10.1136/jnnp.2004.045948 |issn=0022-3050 |pmid=15965199|doi-access=free |pmc=1739710 }}{{Cite journal |last1=Guenther |first1=Frank H. |last2=Ghosh |first2=Satrajit S. |last3=Tourville |first3=Jason A. |date=2006-03-01 |title=Neural modeling and imaging of the cortical interactions underlying syllable production |journal=Brain and Language |volume=96 |issue=3 |pages=280–301 |doi=10.1016/j.bandl.2005.06.001 |pmid=16040108 |issn=0093-934X|pmc=1473986 }}

In the seventeenth and eighteenth centuries, the term corpus striatum was used to designate many distinct, deep, infracortical elements of the{{which|date=April 2024}} hemisphere.Raymond Vieussens, 1685 Etymologically, it is derived from (Latin) striatus {{Cite web|url=https://en.wiktionary.org/wiki/striatus#Latin|title = Striatus|date = 16 August 2019}} = "grooved, striated" and the English striated = having parallel lines or grooves on the surface.{{Cite web|url=https://en.wiktionary.org/wiki/striated|title=Striated|date=9 November 2019}} In 1876 David Ferrier contributed decades of research to the subject; concluding that the corpus striatum was vital in the "organization and generation of voluntary movement".{{Cite journal |last=Hikosaka |first=O. |date=1998 |title=Neural systems for control of voluntary action--a hypothesis |url=https://pubmed.ncbi.nlm.nih.gov/9949766 |journal=Advances in Biophysics |volume=35 |pages=81–102 |doi=10.1016/S0065-227X(98)80004-X |issn=0065-227X |pmid=9949766}}{{Cite journal |last1=Graybiel |first1=Ann M. |last2=Aosaki |first2=Toshihiko |last3=Flaherty |first3=Alice W. |last4=Kimura |first4=Minoru |date=1994-09-23 |title=The Basal Ganglia and Adaptive Motor Control |url=https://www.science.org/doi/10.1126/science.8091209 |journal=Science |language=en |volume=265 |issue=5180 |pages=1826–1831 |doi=10.1126/science.8091209 |pmid=8091209 |bibcode=1994Sci...265.1826G |issn=0036-8075|url-access=subscription }}{{Cite journal |last1=Bromberg-Martin |first1=Ethan S. |last2=Matsumoto |first2=Masayuki |last3=Hikosaka |first3=Okihide |date=2010-12-09 |title=Dopamine in Motivational Control: Rewarding, Aversive, and Alerting |journal=Neuron |language=English |volume=68 |issue=5 |pages=815–834 |doi=10.1016/j.neuron.2010.11.022 |issn=0896-6273 |pmc=3032992 |pmid=21144997}}{{Cite journal |last=Ferrier |first=David |date=1877-07-01 |title=Ferrier on the Functions of the Brain |journal=The British and Foreign Medico-Chirurgical Review |volume=60 |issue=119 |pages=99–114 |pmc=5199255 |pmid=30164726}}{{Cite journal |last1=Kravitz |first1=Alexxai V. |last2=Kreitzer |first2=Anatol C. |date=2012-06-01 |title=Striatal Mechanisms Underlying Movement, Reinforcement, and Punishment |journal=Physiology |volume=27 |issue=3 |pages=167–177 |doi=10.1152/physiol.00004.2012 |issn=1548-9213 |pmc=3880226 |pmid=22689792}} In 1941, Cécile and Oskar Vogt simplified the nomenclature by proposing the term striatum for all elements in the basal ganglia built with striatal elements: the caudate nucleus, the putamen, and the fundus striati,{{cite web|title=NeuroNames Ancillary: fundus striati|url=http://braininfo.rprc.washington.edu/primatebrainmaps/neuronames/ancillary/fundus_striati.html|website=braininfo.rprc.washington.edu|access-date=17 January 2018}} which is the ventral part linking the two preceding together ventrally to the inferior part of the internal capsule.

The term neostriatum was coined by comparative anatomists comparing the subcortical structures between vertebrates, because it was thought to be a phylogenetically newer section of the corpus striatum. The term is still used by some sources, including Medical Subject Headings.{{MeshName|Neostriatum}}

In birds the term used was the paleostriatum augmentatum, and in the new avian terminology listing (as of 2002) for neostriatum this has been changed to the nidopallium.{{cite web|title=New Terminology for the Neostriatum|url=http://www.avianbrain.org/neostriatum.html|website=www.avianbrain.org|access-date=17 January 2018}}

In non-primate species, the islands of Calleja are included in the ventral striatum.

• Cortico-basal ganglia-thalamo-cortical loop
• List of regions in the human brain
• Striatopallidal fibres

File:Striatum coronal sections.gif|Striatum highlighted in green on coronal T1 MRI images

File:Striatum sagittal sections.gif|Striatum highlighted in green on sagittal T1 MRI images

File:Striatum transversal sections.gif|Striatum highlighted in green on transversal T1 MRI images

{{Reflist}}

{{Commons category}}

• {{BrainMaps|striatum}}
• {{BrainInfo|hier|207}}
• {{MeshName|Corpus+Striatum}}
• https://web.archive.org/web/20131029195257/http://www.nimh.nih.gov/images/news-items/r1_braindorsal1.jpg
• https://web.archive.org/web/20090914200329/http://www.hnl.bcm.tmc.edu/fmri.html

{{Basal ganglia}}

{{Neural tracts}}

{{Obsessive–compulsive disorder}}

{{Authority control}}

Category:Cerebrum

Category:Basal ganglia

Category:Addiction