The relationship between the claustrum and endopiriform nucleus: A perspective towards consensus on cross‐species homology

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.

Gad1‐promotor‐driven GFP expression in non‐GABAergic neurons of the nucleus endopiriformis in a transgenic mouse line

“…The nucleus endopiriformis as that brain structure with the highest density of GFP pos neurons was identified by three different approaches: (a) anatomical comparison with the corresponding coronal, sagittal, and horizontal sections of a stereotactic atlas of the mouse brain (Franklin & Paxinos, ), (b) analysis of PV expression pattern in the claustrum and endopiriform nucleus, and (c) by analysis of projections from the cingulate cortex to the nucleus endopiriformis or claustrum via DiI labeling. In agreement with previous reports (Kim, Matney, Roth, & Brown, ; Real et al, ; Smith et al, ; Wójcik et al, ), we only found scarce PV immunoreactivity in the area with the highest density of GFP pos neurons, supporting our finding that GFP pos neurons are located within the nucleus endopiriformis. Moreover, analysis of DiI labeling of cingulate cortex projection neurons revealed DiI‐positive fibers in close vicinity to GFP pos EPP neurons.…”

“…Moreover, analysis of DiI labeling of cingulate cortex projection neurons revealed DiI‐positive fibers in close vicinity to GFP pos EPP neurons. Strong connectivity between the cingulate cortex and the claustrum–endopiriform complex was reported previously (Behan & Haberly, ; Condé et al, ; Qadir et al, ; Smith et al, ; Wang et al, ; Watson et al, ; White et al, ; Zingg et al, ), confirming our observations that these GFP pos neurons are located within the endopiriform nucleus. The endopiriform nucleus is strongly connected to the amygdaloid complex, therefore retrograde labeling of amygdalar projection neurons could further corroborate our finding that GFP pos neurons are located within the endopiriform nucleus (Majak et al, ).…”

“…In agreement with previous reports on PV expression in the nucleus endopiriformis (Real, Dávila, & Guirado, ; Wang et al, ), we only found scarce immunoreactivity to PV in the region with the highest density of GFP pos neurons (Figure b). Furthermore, previous studies reported on a strong connectivity between the claustrum–endopiriform complex and the anterior cingulate and infralimbic cortex (Behan & Haberly, ; Condé, Maire‐Lepoivre, Audinat, & Crépel, ; Qadir et al, ; Smith et al, ; Wang et al, ; Watson et al, ; White et al, ; Zingg, Dong, Tao, & Zhang, ). Therefore, we injected a DiI crystal into the anterior cingulate cortex and determined the presence of DiI‐positive fibers in the area with the highest density of GFP pos neurons (Supporting Information Figure S2).…”

“…Moreover, we found that αCaMKII pos and GAD65/67 pos cells were present at a ratio of around 9:1 (4,105 αCaMKII pos cells vs. 430 GAD65/67 pos cells) within the nucleus endopiriformis (Figure c). Given the fact that the nucleus endopiriformis is discussed to be part of the ventral claustrum (Kowiański, Dziewiatkowski, Kowiańska, & Moryś, ; Majak, Pikkarainen, Kemppainen, Jolkkonen, & Pitkänen, ; Majak et al, ; Mathur, ; Smith et al, ; Watson & Puelles, ; Watson et al, ) and that the claustrum and nucleus endopiriformis exhibit a similar degree of connectivity (Behan & Haberly, ; Majak & Moryś, ; Watson et al, ), this ratio is in good agreement with previous reports showing that around 6–12% of all claustral neurons are GABAergic interneurons (Braak & Braak, ; Gómez‐Urquijo, Gutiérrez‐Ibarluzea, Bueno‐López, & Reblet, ; Kowiański et al, ). To answer the question of whether these GFP pos EPP neurons were born as GABAergic interneurons and only adopted a glutamatergic phenotype later in development, we performed immunolabelings for GFP, GAD65/67, SOM, and αCaMKII at postnatal day one (P1).…”

“…Despite the fact that also their electrophysiological properties differ greatly, it is possible to distinguish them clearly from pyramidal neurons or from PV pos interneurons (Kawaguchi & Kubota, ; Riedemann et al, ). In the study presented here, we report on GFP labeling deep to the cortical projection neurons of the GIN mouse leading to the delineation of the dorsal nucleus endopiriformis (Majak & Moryś, ; Mathur, ; Smith et al, ; Watson, Smith, & Alloway, ). We refer to these GFP pos neurons in the nucleus endopiriformis as endopiriform population (EPP) to distinguish them from SOM pos GIN in other brain areas.…”