A Re-evaluation of the Anatomy of the Claustrum in Rodents and Primates-Analyzing the Effect of Pallial Expansion

Abstract

The components of the claustrum have been identified by gene expression in mice, but there is still uncertainty about the location of homologous components in primates. To aid interpretation of homologous elements between rodents and primates, we used a current understanding of pallial topology, species-specific telencephalic deformation, and gene expression data. In both rodents and primates, pallial areas maintain conserved topological relationships regardless of relative differences in pallial expansion. The components of the claustrum in primates can, therefore, be identified on the basis of their conserved topological relationships and patterns of gene expression. In rodents, a fairly straight telencephalic long axis runs between the early septopreoptic and amygdalar poles of the pallium. In primates, however, the remarkable dorsal pallial expansion causes this axis to be distorted to form a C shape. This has resulted in a number of errors in the interpretation of the location of claustral components. These errors are likely to have resulted from the unexpected topographical positioning of claustral components due to the bent telencephalic axis. We argue that, once the telencephalic distortion has been accounted for, both rodents and primates have homologous claustral components, and that the topological relationships of these components are conserved regardless of differences in the relative expansion of pallial areas.

Keywords: claustrum; dorsal endopiriform nucleus; macaque; organization; rodent.

Figure 1

Organization of the claustrum in the macaque, marmoset and rat. A series of diagrams of coronal sections of primate and rodent brains to illustrate the commonly accepted view of the relative size and position of the components of the claustrum and their relationship to neighboring structures. In each diagram the principal claustrum is colored purple, the dorsal endopiriform nucleus (DEn) is colored beige, the ventral endopiriform nucleus is colored brown, the amygdala is colored cyan, the anterior commissure is colored gray, and the caudate-putamen and cortex are not colored. This diagram is adapted from Figure 1 in Smith et al. (2018).

Figure 2

Pallial organization in amniotes. Panel (A) is a schematic transverse section through the developing telencephalon. The pallium is divided into the medial pallium (MP; violet), dorsal pallium (DP; blue), lateral pallium (LP; yellow), and ventral pallium (VP; red). Cingulate mesocortex (CgMC; green) lies intercalated between MP and DP. The light-yellow structure inside the red VP area represents the DEn, a population that migrates from the claustral anlage in the LP, whereas the red superficial corticoid formation is the olfactory cortex. The principal claustrum (ClP) is the light-yellow oval-shaped area found within LP, while the overlying yellow part of the cortical plate represents the insular cortex. Panel (B) is a planar flattened view of the pallial telencephalon, using the same color codes for the pallial sectors. Note that the circulate mesocortex is represented as closing medially the half ring of the LP, whereas the MP closes the half ring of the VP. The white domain rostromedial to the MP represents the rostral septal pallium domain (SeP, seen in A below the MP and above the psb). The pallial amygdala (AmP) representing the topologic caudal hemispheric pole lies outside the MP/VP ring. Note that the distinguished pallial sectors show clearcut topological relationships, both dorso-ventrally (A, cross section) and rostro-caudally (B, flattened cortex; septo-amygdalar axis). These relationships are kept invariant throughout morphogenesis irrespective of any deformation suffered by the long axis of the telencephalon. Abbreviations: pallial/subpallial boundary (psb), pallidum (Pal), striatum (Str), amygdalar pole (AmP), olfactory bulb (olb; light-red), pallial septum (SeP), subpallial septum (SeSP). Adapted from Puelles (2011).

Figure 3

Incipient axial bending in the mammalian telencephalon, divided into pallial regions. This schema represents the pallial bauplan showing medial (MP; violet), dorsal (DP; blue), lateral (LP; yellow), and ventral (VP; red) pallial regions. The cingulate mesocortex (CgMC; green) is included as well, so that MP and VP form the external allopallial ring, while CgMC and LP form the transitional mesopallial ring that encloses the central DP island. The schema shows how the flat pallial map shown in Figure 1 can be visualized in a lateral view at an embryonic stage in which the septal and amygdalar poles of the hemisphere (Septal Pole; AmP) start to be pushed downwards by differential growth of the DP (isocortex). This incipient deformation carries with it the other components of the pallial map, which result similarly stretched into a curved inverted C-shaped arrangement. Each pallial region nevertheless maintains its fundamental dorso-ventral and rostro-caudal topology throughout the ensuing morphogenetic process. Abbreviations: pallial/subpallial boundary (psb), pallidum (Pal), striatum (Str), diagonal domain (Dg), preoptic area (Poa), pallial septum (SeP), subpallial septum (SeSP), olfactory bulb (olb). This figure was adapted from an illustration in Nieuwenhuys et al. (2008).

Figure 4

Comparison of the lateral pallium (LP) long axis in a rodent (A) and a primate (B). These schemata represent the invariant position of the insular/perirhinal mesocortex (LP) relative to the olfactory cortex (ventral pallium, VP) and the primary septal and amygdalar poles of the hemisphere in a rodent (A) and in a primate (B). The length axis of the rodent LP enclosing the claustroinsular complex is relatively undistorted (gray arrow, A), whereas the length axis of the primate LP undergoes a complex deformation. The frontal tip of LP points into the posterior orbital region of the frontal lobe, its middle part gets bent upon itself to form the insular cortex, and its caudal tip sharply bends around the medial aspect of the temporal pole (gray arrow, B). Note the VP (red) can be easily distinguished underneath the LP (yellow) in rodents (A), while its topologically invariant position is found in the primate along the insular limen and ending caudally next to the uncal amygdalar complex. Consistently with the deformation suffered by the length axis of LP and VP as the temporal lobe emerges, the conserved topologic dorsoventral dimension now points from the insula into the insular limen. By using the septal and amygdalar poles as reference points, it is evident that the LP, which is dorsal to the amygdaloid pole in a rodent, acquires a quite different relative topography in the temporal lobe in primates. In primates, the long axes of both the LP and VP start flat rostrally, approximately on the horizontal plane, but becomes oriented vertically as the axis curves under the temporal pole and reaches the underside of the temporal cortex.

Figure 5

The claustrum shows core and shell expression in mice. This figure shows the expression of Crym (A), Synpr (B), Nr4a2 (C) and Ntng2 (D) in the mouse claustrum. Crym is negative in the dorsal endopiriform nucleus (DEn) but it surrounds the expression of Synpr, Nr4a2 and Ntng2 in the ventral claustrum (VCl). The core and shell is less prominent in the dorsal claustrum (DCl), with the expression of all four markers appearing more evenly distributed. Panel (E) shows the current definition of the DCl, VCl, and DEn based on their representation in the mouse brain atlas of Paxinos and Franklin (2013). Panel (F) shows suggested revisions to the definition of the DCl, VCl, DEn and insular region. The VCl corresponds with the agranular regions, the DCl corresponds with the dysgranular (DI) and granular (GI) insula regions and the DEn corresponds with the piriform cortex (Pir). The area given to the DCl should be expanded to include the complete dorso-lateral expression of Synpr, Nr4a2 and Ntng2. Secondary somatosensory cortex (S2), piriform cortex (Pir), agranular insular cortex dorsal (AID), agranular insular cortex ventral (AIV). Scale bar - 500 μm. Images (A–D) © 2010 Allen Institute for Brain Science. Allen Mouse Brain Atlas (Lein et al., 2007). Available online at: mouse.brain-map.org

Figure 6

The claustrum shows core and shell expression in the macaque. This figure shows the expression of Crym (A,F), Synpr (B,G), Nr4a2 (C,H), Ntng2 (D,I) and Ctgf (E,J) in the macaque claustrum. Panels (A–E) represent sections taken at the level of anterior temporal cortex. Panels (F–J) represent sections taken caudal to the dorsal endopiriform nucleus (DEn). Crym expression forms a shell at the edges of Synpr, Nr4a2 and Ntng2 in the ventral claustrum (VCl) (asterisk, F). The upper portion of the principal claustrum (ClP) has a more even distribution of Crym, Synpr, Nr4a2 and Ntng2, which is homologous with the dorsal claustrum (DCl) in rodents (upper arrows, A–D). There is a lower portion of the ClP that has weaker Synpr, Nr4a2, and Ntng2 expression, appears outside the “shell” region of the VCl and has weak mixed Crym expression (outlined region, F–I). These criteria, alongside the topological argument, identify this region as a continuation of the DCl traveling around and under the temporal cortex (lower arrows, B–D; outlined region, F–I). Panel (E) shows a selective expression of Ctgf in the DEn. The DEn appears directly caudal to the piriform cortex and disappears in further caudal sections (J). Scale bar - 4,200 μm. Images (A–J) © 2009 Allen Institute for Brain Science. NIH Blueprint Non-Human Primate (NHP) Atlas (2009). Available online at: blueprintnhpatlas.org.

Figure 7

The dorsal endopiriform nucleus (DEn) in the macaque. This figure shows the expression of Ctgf (A–D), Ntng2 (E–H), Nr4a2 (I–L), and Synpr (M–P) in the macaque DEn. Note that a coronal section through the temporal cortex may contain entorhinal cortex at the medial surface next to the rhinal fissure, yet may contain periamygdaloid olfactory cortex in a more dorsal location, making it difficult to accurately identify the transition between each area. Ctgf expression is seen in the DEn deep to the piriform cortex (A–D, double arrowhead). The DEn has a caudal part that is topologically inferior to the perirhinal cortex (in this case, medial to the perirhinal cortex) and continues until the periamygdaloid olfactory cortex transitions into the entorhinal cortex (D, double arrowhead). However, while Ctgf is useful for identifying the DEn, it also labels the subplate, and so other claustral markers must be interrogated to accurately separate the dorsal endopiriform and subplate from the claustral components. For example, Ntng2 expression strongly labels the principal claustrum (E–G, single arrowhead), although only weak expression is seen in the topologically caudal claustrum that is found deep of the perirhinal cortex (H, asterisk). The DEn is also strongly labeled (E–H, double arrowhead). Nr4a2 expression clearly shows the caudal aspects of the dorsal claustrum that lie deep to the perirhinal cortex (I–L, asterisk). The DEn is also labeled (J–L, double arrowheads), and maintains a topologically accurate location, deep to the piriform cortex and periamygdaloid olfactory cortex. Synpr expression is present in the DEn (M–P, double arrowhead), particularly the topologically caudal aspects that lie deep to the periamygdaloid olfactory cortex (P, double arrowhead). Symbols and abbreviations: Amyg—amygdala; Pir—piriform cortex; PRh, perirhinal cortex; rf—rhinal fissure; single arrowhead—dorsal claustrum; double arrowhead—dorsal endopiriform nucleus; asterisk—topologically caudal claustrum. Scale bar - 8,400 μm. Images (A–P) © 2009 Allen Institute for Brain Science. NIH Blueprint NHP Atlas (2009). Available online at: blueprintnhpatlas.org.