Structural Connectivity of the Anterior Cingulate Cortex, Claustrum, and the Anterior Insula of the Mouse

Abstract

The claustrum is a narrow subcortical brain structure that resides between the striatum and insular cortex. The function of the claustrum is not fully described, and while our previous work supports a role for the claustrum in top-down cognitive control of action, other evidence suggests the claustrum may be involved in detecting salient changes in the external environment. The anterior cingulate cortex (ACC) and the anterior insular (aINS) are the two major participants in the salience network of human brain regions that activate in response to salient stimuli. While bidirectional connections between the ACC and the claustrum exist from mouse to non-human primate, the aINS connectivity with claustrum remains unclear, particularly in mouse. Here, we explored structural connections of the aINS with the claustrum and ACC through adeno-associated virus neuronal tract tracer injections into the ACC and aINS of the mouse. We detected sparse projections from the claustrum to the aINS and diffuse projections from the aINS to the borders of the claustrum were observed in some cases. In contrast, the insular cortex and endopiriform nucleus surrounding the claustrum had rich interconnectivity with aINS. Additionally, we observed a modest interconnectivity between ACC and the aINS. These data support the idea that claustrum neuron responses to salient stimuli may be driven by the ACC rather than the aINS.

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

“…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, 2003;Wang et al, 2017), we only found scarce immunoreactivity to PV in the region with the highest density of GFP pos neurons (Figure 1b). Furthermore, previous studies reported on a strong connectivity between the claustrumendopiriform complex and the anterior cingulate and infralimbic cortex (Behan & Haberly, 1999;Condé, Maire-Lepoivre, Audinat, & Crépel, 1995;Qadir et al, 2018;Smith et al, 2018;Wang et al, 2017;White et al, 2017;Zingg, Dong, Tao, & Zhang, 2018). 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).…”

Resting State Functional Connectivity of the Rat Claustrum

“…In rats, there does not appear to be anatomical connectivity between the CPu and claustrum (Smith and Alloway, 2010), suggesting that CPu and claustrum should have low RSFC. Some connectivity between Ins and claustrum may exist in in rats (Lipowska et al, 2000; Qadir et al, 2018), which may suggest that some Ins-claustrum FC could have been suppressed with SRCC. Limited RSFC between the claustrum and endopiriform nucleus is also expected given that the endopiriform nucleus and claustrum have distinct anatomical connectivity patterns in mice (Watson et al, 2017; Qadir et al, 2018).…”

“…Each ROI (eight total: bilateral claustrum, Ins, CPu and Endo) was hand drawn on the previously described template brain resliced to 0.3 mm isotropic voxels (Figure 1A). We identified the claustrum based on known anatomical boundaries of the claustrum and used a parvalbumin staining from a separate dataset as a molecular marker for the claustrum (Qadir et al, 2018). The volume of each (i.e., left and right) claustrum was 2.86 mm 3 , or about 18 native resolution voxels.…”

The Claustrum in the Squirrel Monkey

“…A role in attention is implicated by the participation of CLA in resilience to distraction during a behavioral task (Atlan et al, ). Recent work supports a role for CLA in stimulus salience via reciprocal connections with anterior cingulate cortex (Qadir et al, ; White et al, ). All of these theories derive from the assumption that there is a single discoverable function of the CLA that will be the same across species.…”