Editing Claustrum (section)

== Structure ==
The claustrum is a small bilateral [[Grey matter|gray matter]] structure (comprising roughly 0.25% of the cerebral cortex) located deep to the insular cortex and extreme capsule, and superficial to the external capsule and basal ganglia.<ref name="Crick2005" />

Its name means “hidden away”, and was first identified in 1672, with more detailed descriptions coming later on during the 19th century.<ref name="Crick2005" /> Although the regional neuroanatomical boundaries of the claustrum have been defined, there remains a lack of consensus in the literature when defining its precise margins,<ref name="Goll2015" /><ref>{{cite journal | vauthors = Baizer JS, Sherwood CC, Noonan M, Hof PR | title = Comparative organization of the claustrum: what does structure tell us about function? | journal = Frontiers in Systems Neuroscience | volume = 8 | pages = 117 | date = 2014 | pmid = 25071474 | pmc = 4079070 | doi = 10.3389/fnsys.2014.00117 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Mathur BN | title = The claustrum in review | journal = Frontiers in Systems Neuroscience | volume = 8 | pages = 48 | date = 2014 | pmid = 24772070 | pmc = 3983483 | doi = 10.3389/fnsys.2014.00048 | doi-access = free }}</ref> though a meeting in 2019 of experts has posited a framework by which to refer to the structures across species.<ref name="Smith2019"/>

=== Connections ===
An early summary of reports from the 20th century emphasized cortical inputs and outputs.<ref name="Edelstein2004">{{cite journal | vauthors = Edelstein LR, Denaro FJ | title = The claustrum: a historical review of its anatomy, physiology, cytochemistry and functional significance | journal = Cellular and Molecular Biology | volume = 50 | issue = 6 | pages = 675–702 | date = September 2004 | pmid = 15643691 }}</ref> However, later work has suggested the claustrum has extensive connections to cortical and subcortical regions.<ref>{{cite journal | vauthors = Buchanan KJ, Johnson JI | title = Diversity of spatial relationships of the claustrum and insula in branches of the mammalian radiation | journal = Annals of the New York Academy of Sciences | volume = 1225 Suppl 1 | pages = E30-63 | date = May 2011 | issue = S1 | pmid = 21599698 | doi = 10.1111/j.1749-6632.2011.06022.x | bibcode = 2011NYASA1225E..30B | s2cid = 2245096 }}</ref> More specifically, [[Electrophysiology|electrophysiological]] studies show extensive connections to [[List of thalamic nuclei|thalamic nuclei]] and the [[basal ganglia]], while isotopological reports have linked the claustrum with the prefrontal, frontal, parietal, temporal and occipital cortices.<ref>{{cite book |doi=10.1016/B978-0-12-404566-8.00005-2 |chapter=Physiology of the Claustrum |title=The Claustrum |year=2014 |last1=Sherk |first1=Helen |pages=177–191 |isbn=978-0-12-404566-8 }}</ref><ref>{{Cite book | first1 = John R | last1 = Smythies | first2 = Lawrence R | last2 = Edelstein | first3 = V S | last3 = Ramachandran | name-list-style = vanc |title=The claustrum : structural, functional, and clinical neuroscience |date=2014|publisher=Academic Press|isbn=978-0-12-404566-8 |oclc=861211388}}{{page needed|date=September 2020}}</ref> Additional studies have also looked at the relationship of the claustrum to well-described subcortical white matter tracts. Structures such as the [[corona radiata]], [[occipitofrontal fasciculus]] and [[uncinate fasciculus]] project to the claustrum from frontal, pericentral, parietal and occipital regions.<ref>{{cite journal | vauthors = Fernandez-Miranda JC, Pathak S, Engh J, Jarbo K, Verstynen T, Yeh FC, Wang Y, Mintz A, Boada F, Schneider W, Friedlander R | s2cid = 12867524 | title = High-definition fiber tractography of the human brain: neuroanatomical validation and neurosurgical applications | journal = Neurosurgery | volume = 71 | issue = 2 | pages = 430–53 | date = August 2012 | pmid = 22513841 | doi = 10.1227/NEU.0b013e3182592faa }}</ref> Reciprocal connections also exist with motor, [[Somatosensory system|somatosensory]], [[Primary auditory cortex|auditory]] and visual cortical regions.<ref name="Goll2015" /> Altogether, these findings leave the claustrum as the most highly connected structure per regional volume in the brain and suggest that it may serve as a hub to coordinate activity of cerebral circuits.<ref>{{cite journal | vauthors = LeVay S | title = Synaptic organization of claustral and geniculate afferents to the visual cortex of the cat | journal = The Journal of Neuroscience | volume = 6 | issue = 12 | pages = 3564–75 | date = December 1986 | pmid = 2432202 | pmc = 6568649 | doi = 10.1523/JNEUROSCI.06-12-03564.1986 }}</ref><ref>{{cite journal | vauthors = Zingg B, Hintiryan H, Gou L, Song MY, Bay M, Bienkowski MS, Foster NN, Yamashita S, Bowman I, Toga AW, Dong HW | title = Neural networks of the mouse neocortex | journal = Cell | volume = 156 | issue = 5 | pages = 1096–111 | date = February 2014 | pmid = 24581503 | pmc = 4169118 | doi = 10.1016/j.cell.2014.02.023 }}</ref> Even with this extensive connectivity, most projections to and from the claustrum are ipsilateral (although there are still contralateral projections), and little evidence exists to describe its afferent or efferent connections with the brainstem and spinal cord.<ref name="Goll2015" /><ref name="Edelstein2004"/><ref name="Markowitsch1984">{{cite journal | vauthors = Markowitsch HJ, Irle E, Bang-Olsen R, Flindt-Egebak P | title = Claustral efferents to the cat's limbic cortex studied with retrograde and anterograde tracing techniques | journal = Neuroscience | volume = 12 | issue = 2 | pages = 409–25 | date = June 1984 | pmid = 6462456 | doi = 10.1016/0306-4522(84)90062-9 | s2cid = 21613309 }}</ref> In summary, the cortical and subcortical connectivity of the claustrum implies that it is most involved with processing sensory information, as well as the physical and emotional state of an animal.

=== Microanatomy ===
Inputs to the claustrum are organized by modality, which include prefrontal, visual, auditory and [[Somatomotor system|somatomotor]] processing areas. In the same way that the morphology of neurons in the [[Rexed laminae]] of the [[spinal cord]] is indicative of function, the visual, auditory and somatomotor regions within the claustrum share similar neurons with specific functional characteristics. For example, the portion of the claustrum that processes visual information (''primarily synthesizing afferent fibers concerned with our peripheral visual field'') is comprised by a majority of binocular cells that have "elongated receptive fields and no orientation selectivity".<ref name="Smith2010">{{cite journal | vauthors = Smith JB, Alloway KD | title = Functional specificity of claustrum connections in the rat: interhemispheric communication between specific parts of motor cortex | journal = The Journal of Neuroscience | volume = 30 | issue = 50 | pages = 16832–44 | date = December 2010 | pmid = 21159954 | pmc = 3010244 | doi = 10.1523/JNEUROSCI.4438-10.2010 }}</ref><ref>{{cite journal | vauthors = Smith JB, Alloway KD | title = Interhemispheric claustral circuits coordinate sensory and motor cortical areas that regulate exploratory behaviors | journal = Frontiers in Systems Neuroscience | volume = 8 | pages = 93 | date = 2014 | pmid = 24904315 | pmc = 4032913 | doi = 10.3389/fnsys.2014.00093 | doi-access = free }}</ref>

This focus on the peripheral sensory system is not an isolated occurrence, as most sensory afferents entering the claustrum bring peripheral sensory information. Moreover, the claustrum possesses a distinct [[Topology|topological]] organization for each sensory modality as well as the dense connectivity it shares with frontal cortices.<ref name="Shelton-2022" /><ref name="Marriott-2021">{{Cite journal |last1=Marriott |first1=Brian A. |last2=Do |first2=Alison D. |last3=Zahacy |first3=Ryan |last4=Jackson |first4=Jesse |date=2021 |title=Topographic gradients define the projection patterns of the claustrum core and shell in mice |journal=Journal of Comparative Neurology |language=en |volume=529 |issue=7 |pages=1607–1627 |doi=10.1002/cne.25043 |issn=0021-9967 |pmc=8048916 |pmid=32975316}}</ref> For example, there is a retinotopic organization within the visual processing area of the claustrum that mirrors that of visual association cortices and V1, in a similar (yet less complicated) manner to the retinotopic conservation within the lateral geniculate nucleus.<ref name="Goll2015" />

Within the claustrum, local connectivity is dominated by feed-forward disynaptic inhibition wherein [[parvalbumin]]-expressing interneurons suppress the activity of nearby projection neurons.<ref>{{Cite journal |last1=Kim |first1=Juhyun |last2=Matney |first2=Chanel J. |last3=Roth |first3=Richard H. |last4=Brown |first4=Solange P. |date=2016-01-20 |title=Synaptic Organization of the Neuronal Circuits of the Claustrum |url=https://www.jneurosci.org/content/36/3/773 |journal=Journal of Neuroscience |language=en |volume=36 |issue=3 |pages=773–784 |doi=10.1523/JNEUROSCI.3643-15.2016 |issn=0270-6474 |pmid=26791208|pmc=4719014 }}</ref> Local interneurons themselves are connected through both [[Synapse|chemical]] and [[Gap junction|electrical synapses]], allowing for widespread and synchronous inhibition of local claustrum circuitry. In recent studies of the claustrum in [[mice]]<ref name="Shelton-2022" /> and [[bat]]s,<ref>{{Cite journal |last=Orman |first=Rena |date=2015-11-01 |title=Claustrum: a case for directional, excitatory, intrinsic connectivity in the rat |journal=The Journal of Physiological Sciences |language=en |volume=65 |issue=6 |pages=533–544 |doi=10.1007/s12576-015-0391-6 |pmid=26329935 |s2cid=255605784 |issn=1880-6562|doi-access=free |pmc=10717944 }}</ref> cortically-projecting excitatory claustrum neurons were found to form synapses across the anteroposterior axis and were biased toward neurons that do not share projection targets, with the possible function of joining the activity of different afferent modules.<ref name="Marriott-2021" /> Combined, these two circuits suggest that the claustrum is capable of performing local transformations of diverse input information from across the brain.

=== Cell types ===
The claustrum is made up of various cell types that differ in size, shape and neurochemical composition.<ref name="Chau2015" /> Excitatory cell types in the claustrum consist of two main classes which differentially project to [[Cortex (anatomy)|cortical]] and [[Subcortex|subcortical]] brain regions.{{Citation needed|date=September 2023}} Inhibitory neurons represent only 10%-15% of the neurons within the claustrum and consist of three types, expressing [[parvalbumin]], [[Somatostatin receptor 2|somatostatin]] or [[Vasoactive intestinal peptide receptor|vasoactive intestinal peptide]], similar to inhibitory neurons in the cortex.<ref>{{Cite journal|last1=Tremblay|first1=Robin|last2=Lee|first2=Soohyun|last3=Rudy|first3=Bernardo|date=20 July 2016|title=GABAergic interneurons in the neocortex: From cellular properties to circuits|url= |journal=Neuron|volume=91|issue=2|pages=260–292|doi=10.1016/j.neuron.2016.06.033|pmid=27477017|pmc=4980915|doi-access=free}}</ref> Finally, many studies show that the claustrum is best distinguished structurally by its prominent plexus of parvalbumin-positive fibers formed by parvalbumin-expressing inhibitory cell types.<ref name="Brown" /> In recent studies, the use of [[myelin basic protein]] (MBP) and retrogradely traveling [[cholera toxin]] have additionally been used as effective methods of identifying the claustrum.<ref name="Marriott-2021" /><ref>{{Cite journal |last1=Wang |first1=Quanxin |last2=Wang |first2=Yun |last3=Kuo |first3=Hsien-Chi |last4=Xie |first4=Peng |last5=Kuang |first5=Xiuli |last6=Hirokawa |first6=Karla E. |last7=Naeemi |first7=Maitham |last8=Yao |first8=Shenqin |last9=Mallory |first9=Matt |last10=Ouellette |first10=Ben |last11=Lesnar |first11=Phil |last12=Li |first12=Yaoyao |last13=Ye |first13=Min |last14=Chen |first14=Chao |last15=Xiong |first15=Wei |date=2023-02-28 |title=Regional and cell-type-specific afferent and efferent projections of the mouse claustrum  |journal=Cell Reports |volume=42 |issue=2 |pages=112118 |doi=10.1016/j.celrep.2023.112118 |pmid=36774552 |pmc=10415534 |issn=2211-1247 }}</ref>

Several approaches in [[mice]] have been used to assess claustrum cell types, including electrophysiological, morphological, genetic, and connectomic approaches.<ref name="Shelton-2022">{{Cite journal |last1=Shelton |first1=Andrew |last2=Oliver |first2=David |last3=Grimstvedt |first3=Joachim |last4=Lazarte |first4=Ivan |last5=Kapoor |first5=Ishaan |last6=Clifford |first6=Kentros |last7=Witter |first7=Menno |last8=Butt |first8=Simon |last9=Packer |first9=Adam |date=2022 |title=Single neurons and networks in the claustrum integrate input from widespread cortical sources |url=https://www.biorxiv.org/content/10.1101/2022.05.06.490864v1 |website=bioRxiv|doi=10.1101/2022.05.06.490864 |s2cid=248672084 }}</ref><ref name="Marriott-2021" /><ref name="Qadir-2022">{{Cite journal |last1=Qadir |first1=Houman |last2=Stewart |first2=Brent W. |last3=VanRyzin |first3=Jonathan W. |last4=Wu |first4=Qiong |last5=Chen |first5=Shuo |last6=Seminowicz |first6=David A. |last7=Mathur |first7=Brian N. |date=2022-12-20 |title=The mouse claustrum synaptically connects cortical network motifs |journal=Cell Reports |volume=41 |issue=12 |pages=111860 |doi=10.1016/j.celrep.2022.111860 |pmid=36543121 |pmc=9838879 |issn=2211-1247}}</ref><ref>{{Cite journal |last1=Graf |first1=Martin |last2=Nair |first2=Aditya |last3=Wong |first3=Kelly L. L. |last4=Tang |first4=Yanxia |last5=Augustine |first5=George J. |date=2020-07-01 |title=Identification of Mouse Claustral Neuron Types Based on Their Intrinsic Electrical Properties |url=https://www.eneuro.org/content/7/4/ENEURO.0216-20.2020 |journal=eNeuro |language=en |volume=7 |issue=4 |doi=10.1523/ENEURO.0216-20.2020 |issn=2373-2822 |pmid=32527746|pmc=7405070 }}</ref><ref>{{Cite journal |last1=Erwin |first1=Sarah R |last2=Bristow |first2=Brianna N |last3=Sullivan |first3=Kaitlin E |last4=Kendrick |first4=Rennie M |last5=Marriott |first5=Brian |last6=Wang |first6=Lihua |last7=Clements |first7=Jody |last8=Lemire |first8=Andrew L |last9=Jackson |first9=Jesse |last10=Cembrowski |first10=Mark S |date=2021-08-16 |editor-last=Mao |editor-first=Tianyi |editor2-last=Westbrook |editor2-first=Gary L |editor3-last=Zhang |editor3-first=Li I |title=Spatially patterned excitatory neuron subtypes and projections of the claustrum |journal=eLife |volume=10 |pages=e68967 |doi=10.7554/eLife.68967 |pmid=34397382 |pmc=8367382 |issn=2050-084X |doi-access=free }}</ref> While no clear consensus has yet been reached regarding the exact number of excitatory cell types, recent studies have suggested that cortically- and subcortically-projecting claustrum neurons are likely distinct and vary along several metrics, such as their intrinsic electrophysiological profiles, afferent projections, and neuromodulatory profiles.<ref name="Shelton-2022" /><ref name="Qadir-2022" /><ref>{{Cite journal |last1=Nair |first1=Aditya |last2=Teo |first2=Yue Yang |last3=Augustine |first3=George J. |last4=Graf |first4=Martin |date=2023-07-11 |title=A functional logic for neurotransmitter corelease in the cholinergic forebrain pathway |journal=Proceedings of the National Academy of Sciences |language=en |volume=120 |issue=28 |pages=e2218830120 |doi=10.1073/pnas.2218830120 |issn=0027-8424 |pmc=10334726 |pmid=37399414|bibcode=2023PNAS..12018830N }}</ref>