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Review
. 2019 Feb 1;527(2):476-499.
doi: 10.1002/cne.24537. Epub 2018 Nov 18.

The Relationship Between the Claustrum and Endopiriform Nucleus: A Perspective Towards Consensus on Cross-Species Homology

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Free PMC article
Review

The Relationship Between the Claustrum and Endopiriform Nucleus: A Perspective Towards Consensus on Cross-Species Homology

Jared B Smith et al. J Comp Neurol. .
Free PMC article

Abstract

With the emergence of interest in studying the claustrum, a recent special issue of the Journal of Comparative Neurology dedicated to the claustrum (Volume 525, Issue 6, pp. 1313-1513) brought to light questions concerning the relationship between the claustrum (CLA) and a region immediately ventral known as the endopiriform nucleus (En). These structures have been identified as separate entities in rodents but appear as a single continuous structure in primates. During the recent Society for Claustrum Research meeting, a panel of experts presented data pertaining to the relationship of these regions and held a discussion on whether the CLA and En should be considered (a) separate unrelated structures, (b) separate nuclei within the same formation, or (c) subregions of a continuous structure. This review article summarizes that discussion, presenting comparisons of the cytoarchitecture, neurochemical profiles, genetic markers, and anatomical connectivity of the CLA and En across several mammalian species. In rodents, we conclude that the CLA and the dorsal endopiriform nucleus (DEn) are subregions of a larger complex, which likely performs analogous computations and exert similar effects on their respective cortical targets (e.g., sensorimotor versus limbic). Moving forward, we recommend that the field retain the nomenclature currently employed for this region but should continue to examine the delineation of these structures across different species. Using thorough descriptions of a variety of anatomical features, this review offers a clear definition of the CLA and En in rodents, which provides a framework for identifying homologous structures in primates.

Keywords: claustrum; endopiriform; homology; human; primate; rodent.

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest regarding the content of this article.

Figures

FIGURE 1.
FIGURE 1.
Coronal sections from brain atlases for human (Mai et al., 2016), macaque (Paxinos et al., 2000), marmoset (Paxinos et al., 2012), bat (Scalia, Rasweiler, Scalia, Orman, & Stewart, 2013), and rat (Paxinos & Watson, 2007) showing the delineation of the claustrum (purple), dorsal endopiriform nucleus (beige), ventral endopiriform nuclei (brown), amygdala (cyan), caudate-putamen (white), cortex (white) and anterior commissure (grey). Note the lack of endopiriform designation in human and the obscure location of endopiriform nucleus in macaque compared to other species.
FIGURE 2.
FIGURE 2.
Cytoarchitecture, neurochemical topography, and gene expression profile of CLA and En in rat. (a) Nissl-stained coronal section of rat brain showing the dorsal and ventral parts of the claustrum (dCLA, vCLA, arrows) and dorsal endopiriform nucleus (DEn, arrowheads), note the decreased cell packing density in DEn. (b) Patterns of neurochemical labeling for parvalbumin, cytochrome oxidase, and acetylcholine esterase (AChE) throughout CLA and DEn in rat. (c-l) Coronal sections revealing the expression of different gene markers using in situ hybridization for nurr1 (c, h), latexin (d, i), Ntng2 (e, j), GNB4 (f, k) relative to the location of the dCLA, vCLA, DEn, and ventral endopiriform nucleus (VEn) as identified by Nissl (g, l). These data show strong expression of each marker in dCLA, vCLA and DEn, whereas VEn shows no expression for any of these markers. (m) Color plot of gene expression for 47 genes listed in Table 4 (from Wang et al., 2017). Note that almost all genes are expressed in dCLA, vCLA, and DEn, but not in VEn. Panels (a) and (b) modified from Watson, Smith, & Alloway, 2017. Panels (c-l) modified from Watakabe, 2017. ac: anterior commissure; dCLA: dorsal claustrum; DEn: dorsal endopiriform nucleus; Pir: piriform cortex; rf: rhinal fissure; vCLA: ventral claustrum; VEn: ventral endopiriform nucleus. Scale bars = 500 μm in (a); 1 mm in (c-g); 250 μm in (h-l).
FIGURE 3.
FIGURE 3.
Embryological expression of CLA-specific genes indicates a common origin for CLA and DEn in rodent. (a) Divisions of the mammalian embryo, with subdivisions of the pallium identified by gene expression (note the updated nomenclature from Wullimann, 2017). (b) Developmental studies of Nr4a2 (a Nurr family gene) indicate a common origin of CLA and DEn in the ventrolateral dorsal pallium, the same subregion that later gives rise to the insular cortex. During development, DEn cells migrate ventrally into the lateral pallium to take their final position in the adult brain next to piriform cortex, which itself originated in the lateral pallium. Also note the separate embryological origin of the VEn in the lateral pallium, indicating it is not related to the CLA-DEn complex. Modified from Watson & Puelles, 2017 and Wullimann, 2017. CLA: claustrum; DEn: dorsal endopiriform nucleus; DMS: dorsal migratory stream; MGE: medial ganglionic eminence; LGE: lateral ganglionic eminence; VEn: ventral endopiriform nucleus; VMS; ventral migratory stream.
FIGURE 4.
FIGURE 4.
Topography of connectivity between cortex and CLA in rodents and primates. (a) Top panel shows the general topographic organization of CLA connections with cortex in rat, as identified by traditional retrograde tracing from cortex, which reveals a dorsal somatomotor area and a ventral visuo-auditory area (modified from Sadowski, Moryś, Jakubowska-Sadowska, & Narkiewicz, 1997). A similar topography is shown in mouse in the bottom panel, as mapped by modern viral tracing techniques, revealing olfactory bulb (allocortex) inputs to a more ventral region of CLA, likely DEn (modified from Atlan et al., 2017). (b) Highly conserved dorsoventral topography in the primate CLA with somatomotor areas represent in dorsal CLA, associative areas in central CLA, and visuo-auditory areas located in ventral regions of CLA, as revealed by the horseradish peroxidase tracing method (modified from Pearson, Brodal, Gatter, & Powell, 1982). Note that each area in primate goes to a region of motor and sensory cortex. Numbers in cortical injection sites indicate Brodmann area. (c) Topography from two electrophysiology studies in primates, which functionally confirm unimodal processing in compartment specific regions of CLA (compiled from Shima et al., 1991 and Remedios, Logothetis, & Kayser, 2010). Note the mismatch in location of auditory regions of CLA between the anatomical tracing (b) and electrophysiology data (c). CLA: claustrum; DEn: dorsal endopiriform nucleus.
FIGURE 5.
FIGURE 5.
Similarities in anatomical connectivity of CLA and DEn in rat. (a) Diagram illustrating the dorsoventral topographic relationship of CLA to somatomotor regions dorsally and visuomotor regions ventrally, whereas DEn connects to limbic cortical areas. (b) Both CLA and DEn have extensive intranuclear longitudinal connectivity that retain separate dorsal (purple arrows) and ventral (orange arrows) domains within their respective nuclei. (c) Circuit diagrams showing the same pattern of intra- and interhemispheric sensorimotor connections of the rodent CLA (purple arrows) compared to the limbic connections of the rodent endopiriform nucleus (orange arrows). (d) Both CLA and DEn have the same pattern of input-output connectivity with the different layers of cortex. Specifically, inputs to the CLA-DEn complex originate from layers 2 5 of frontal and higher-order sensory cortical areas, but from layer 6 of primary sensory cortical areas. The CLA-DEn complex in turn innervates all layers of cortex, with a much stronger innervation of frontal cortices. Inset shows photomicrograph of anterogradely labeled claustrocortical terminals that appear as small “mushroom-like” terminal boutons that extend from the axon. Based on Alloway, Smith, Beauchemin, & Olson, 2009; Smith & Alloway, 2010, ; Smith, Radharikistan, & Alloway, 2012; Watson, Smith, & Alloway 2017. Image of claustrocortical terminals modified from Smith, Liang, Watson, Alloway, & Zhang, 2017. AGl: agranular lateral cortex; AGm: agranular medial cortex; Cg: cingulate cortex; CLA: claustrum; DEn: dorsal endopiriform nucleus; M1: primary motor cortex; M2: secondary motor cortex; mPFC: medial prefrontal cortex; S1: primary somatosensory cortex. Scale bar = 2 μm.
FIGURE 6.
FIGURE 6.
Delineation of the CLA-En complex in marmosets. Series of coronal sections of a marmoset brain stained for Nissl (panels a-d) or for Nurr1 gene expression by in situ hybridization (panels e-h). The red dotted line indicates the location of the CLA-DEn complex, a cell-dense nucleus with strong Nurr1 signals. The positions of the IEn and VEn are based on a marmoset atlas and may not represent the true homologues of their rodent counterparts (Paxinos et al., 2000). ac: anterior commissure; Amy: amygdala; CLA: claustrum; DEn: dorsal endopiriform nucleus; IEn: intermediate endopiriform nucleus; VEn: ventral endopiriform nucleus; Pir; piriform cortex. Scale bars = 1 mm.
FIGURE 7.
FIGURE 7.
Identification CLA-DEn complex in a primate with gene marker expression and histological staining. (a-y) Images of serial coronal sections of a Japanese monkey brain stained for cytochrome oxidase (CO; a-e), acetylcholine esterase (AChE; f-j), VGluT1 in situ hybridization (ISH; k-o) Nurr1-ISH (p-t), and Nissl staining (u-y). Modified from Watakabe, Ichinohe, & Noritaka, 2007. Coronal sections were sliced at 40 μm intervals and stained periodically (one every 2 mm). Numbers in the bottom right corner of each panel indicate the serial section numbers starting from the top left panel. Scale bars = 10 mm.
FIGURE 8:
FIGURE 8:
Gene expression and white matter tracts clearly delineate the border between CLA-DEn complex and amygdaloid complex in primates. (a-y) Higher magnification images of serial coronal sections of a Japanese monkey brain from Figure 7 showing the CLA-DEn amygdala border by staining for cytochrome oxidase (CO; a-e), acetylcholine esterase (AChE; f-j), VGluT1-in situ hybridization (ISH; k-o) Nurr1 ISH (p-t), and Nissl staining (u-y). For the bottom panels denoted as “###T”, the tracing was manually done based on Nissl staining and annotated according to the staining patterns and morphological features from the rhesus monkey atlas (Paxinos et al., 2000). The red arrows indicate the putative border between the CLA-DEn complex and the amygdala-related complex. The asterisks indicate the putative brain area for the VEn (which could actually be part of amygdalar complex). ac: anterior commissure; BL: basolateral nucleus of amygdala; BM: basomedial nucleus of amygdala; CLA: claustrum; DEn: dorsal endopiriform nucleus; L: lateral nucleus of amygdala; Pir: piriform cortex; PLBL: paralamellar basolateral nucleus of amygdala. Scale bars = 2.5 mm.
FIGURE 9
FIGURE 9
Preliminary myeloarchitecture-based parcellation of the marmoset claustrum complex. Gallyas stained section, approximate A-P coordinate +9.5 mm. The CLA portion of the claustrum complex is outlined in blue, while the DEn is marked in yellow. Note increasing myelin density along the dorsoventral axis. Numerous cut myelinated fibers in DEnV indicate axons running longitudinally along the coronal plane of section. Red arrowheads indicate the myelin boundary between the CLA and dorsolateral extent of the amygdaloid complex. Nomenclature and labeling follow conventions of Paxinos et al. 2012, with the exception of newly identified subdivisions of DEn. ac: anterior commissure; CLA: claustrum; DEnD: dorsal subdivision of the DEn; DEnI: intermediate subdivision of the DEn; DEnV: ventral subdivision of the DEn; ec: external capsule; ex: extreme capsule; Ins: insular cortex; L: lateral amygdala; Pu: putamen;. Scale bar = 1mm.
FIGURE 10.
FIGURE 10.
Neurochemical identification of the CLA-DEn complex in a fruit bat. (a-e) Low magnification comparison of CLA and DEn in coronal sections. Immunohistochemistry in each panel is labeled showing NeuN-(a), latexin (b), parvalbumin (c), calretinin (d), and vascularization with rhodamine (e). Red arrows mark the lateral border of CLA. Yellow arrows mark the lateral and ventrolateral border of DEn. The medial border of both structures is demarcated by the white matter of the external capsule. The dense packing of cells in CLA is best seen in NeuN-(a) and latexin-immunolabeled sections (b), but these antibodies do not differentiate CLA from DEn. However, antibodies for the calcium-binding proteins parvalbumin (c) and calretinin (d) clearly show different patterns for these nuclei. Panel e shows the bat brain vasculature via transcardially perfusions with rhodamine-conjugated gelatin before sectioning (images obtained in collaboration with T. Ragan and M. Marek, TissueVision, Somerville, MA). (f-j) High magnification of CLA from each panel in the top row. (k-o) High magnification of DEn from each panel in the top row. The presence of PV-ir neurons in claustrum (h) and calretinin-ir neurons in DEn (n) are also highlighted in these higher magnification images. Scale bar = 2 mm.

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