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.
Highlights
Many cortical areas bidirectionally connect with the claustrum across mammalian species, including primate (Bianchi, 1922; Rae, 1954; Markov et al, 2011; Reser et al, 2014), cat (LeVay and Sherk, 1981; Markowitsch et al, 1984; Witter et al, 1988), rat (White et al, 2017), and mouse (Wang et al, 2017)
The present results indicate that the mouse claustrum weakly, if at all, projects to the anterior insular cortex (aINS)
The endopiriform nucleus is bidirectionally connected with the aINS
Summary
Many cortical areas bidirectionally connect with the claustrum across mammalian species, including primate (Bianchi, 1922; Rae, 1954; Markov et al, 2011; Reser et al, 2014), cat (LeVay and Sherk, 1981; Markowitsch et al, 1984; Witter et al, 1988), rat (White et al, 2017), and mouse (Wang et al, 2017). In the rat and rabbit, connections from the aINS and endopiriform nucleus to the dorsal claustrum region were detected (Lipowska et al, 2000) One reason for these discrepancies may be that the anatomical boundaries of the claustrum in these studies were not defined by data-driven anatomical criteria. To describe the mouse structural connections between the aINS, ACC, and claustrum, in this study we injected one adeno-associated virus (AAV) expressing a green fluorophore into the ACC and another AAV virus expressing a red fluorophore into the aINS, and vice versa. Both viruses exhibit both anterograde and retrograde trafficking properties (Tervo et al, 2016). Laboratory Animals and the University of Maryland, School of Medicine Animal Care and Use Committee
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