Proteomic Analysis Illuminates a Novel Structural Definition of the Claustrum and Insula

Abstract

The claustrum is a prominent but ill-defined forebrain structure that has been suggested to integrate multisensory information and perhaps transform percepts into consciousness. The claustrum's shape and vague borders have hampered experimental assessment of its functions. We used matrix-assisted laser desorption ionization-imaging mass spectrometry to reveal a novel protein marker, G-protein gamma2 subunit (Gng2), which is enriched in the claustrum but not adjacent structures of the rat forebrain. The spatial pattern of Gng2 expression suggests key differences from commonly held views of the claustrum's structure. Using anatomical methods, we found that the rat claustrum is present only at striatal levels of the telencephalon and does not extend to frontal cortical territories. Moreover, the claustrum is surrounded on all sides by layer VI insular cortex cells in both the rat and primate. Using these defining characteristics of the claustrum, we found that the claustrum projects to cortical but not to subcortical sites. The definition of the claustrum as a cortical site is considered. The identification of a claustrum-specific protein opens the door to selective molecular lesions and the subsequent evaluation of the role of the claustrum in cognition.

The Synaptic Organization of the Claustral Projection to the Cat's Visual Cortex

“…These results were then reproduced in many other mammal species, including the tractography evidence from humans (Morys et al, 1993;Fernández-Miranda et al, 2008). Injections in the claustrum also labeled numerous subcortical structures such as the putamen, zona incerta, dorsomedial thalamus, the suprageniculate thalamus, and hypothalamus (LeVay and Sherk, 1981b;Markowitsch et al, 1984;Erickson and Lewis, 2004;Yoshida et al, 2006) (but see Mathur et al, 2009). This comprehensive connectivity is well suited to its name, which is derived from monastic architecture and refers to the broad passage that gives access to all the buildings and apartments of a monastery.…”

The claustrum: Considerations regarding its anatomy, functions and a programme for research

“…(b) Gnb4 (Guanine nucleotide binding protein (G protein), beta 4) expression is enriched in the claustrum throughout the claustrum (Wang et al, 2017), including its rostral extent as defined by the Cyrm template in (a). (c) Gng2 (guanine nucleotide binding protein (G protein), gamma 2) expression is enriched in the claustrum (Mathur et al, 2009), again extending rostral to the anterior apex of the striatum. (d) Lxn (Latexin) expression is also enriched throughout the claustrum including its rostral extent.…”

Imaging Mass Spectrometry of Proteins and Peptides

“…This protein was subsequently identified (via traditional tissue homogenization, fractionation, and tryptic digestion) as g-protein gamma2 subunit (gng2). Figure 10.6E,F shows the Ihc validation of the MS data, showing gng is enriched in the claustrum only at striatal levels (F) and not at frontal levels (E) [48]. one advantage illustrated by …”

“…MALDI imaging may provide a useful complement for the study of this subset of lower molecular weight proteins (<30,000 Da). IMS was recently used to redefine a small region of the brain called the claustrum [48]. The claustrum is a prominent but ill-defined forebrain structure thought to be involved with integration of multisensory information; however, its vague borders have made experimental assessment of its functions difficult.…”