Abstract
The insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here, we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. We employed cell-type-specific monosynaptic rabies virus tracings to characterize afferent connections onto either excitatory or inhibitory IC neurons, and adeno-associated viral tracings to label excitatory efferent axons. While the connectivity between the IC and other cortical regions was highly bidirectional, the IC connectivity with subcortical structures was often unidirectional, revealing prominent cortical-to-subcortical or subcortical-to-cortical pathways. The posterior and medial IC exhibited resembling connectivity patterns, while the anterior IC connectivity was distinct, suggesting two major functional compartments. Our results provide insights into the anatomical architecture of the mouse IC and thus a structural basis to guide investigations into its complex functions.
Highlights
The most anterior region, aIC ranged from +2.45 mm to +1.20 mm from Bregma; the medial part, mIC, from +1.20 mm to +0.01 mm from Bregma, and the posterior part, pIC, from +0.01 mm to -1.22 mm from Bregma
Consistent with a previous study (Hunnicutt et al, 2016), we found that the ventral regions of the striatum were more innervated by insular cortex (IC) projections than dorsal regions (Fig 4b)
We found a large difference in the innervation of the striatum along the rostrocaudal axis of the insula, with the aIC providing the strongest projections
Summary
The insular cortex (IC or insula) has been suggested to mediate a wide variety of brain functions, such as the processing of external and bodily sensory information (Kurth, Zilles, Fox, Laird, &Eickhoff, 2010), bodily- and self-awareness (Craig, 2009; Craig, 2011), emotion regulation (Etkin, Büchel, & Gross, 2015), feelings and complex social-affective functions like empathy (Damasio & Carvalho, 2013), and switches between large-scale brain networks (Menon & Uddin, 2010).Rodent studies further demonstrated roles for the IC in multisensory (Gogolla, Takesian, Feng, Fagiolini, & Hensch, 2014; Rodgers, Benison, Klein, & Barth, 2008) and pain processing (Tan et al, 2017), representation of valence (Wang et al, 2018), learning and memory (Bermúdez-Rattoni, Okuda, Roozendaal, & McGaugh, 2005; Lavi, Jacobson, Rosenblum, & Lüthi, 2018), social interactions (Rogers-Carter et al, 2018), gustation (Peng et al, 2015; Wang et al, 2018), drug cravings and malaise (Contreras, Ceric, & Torrealba, 2007), and aversive states such as hunger, thirst, and anxiety (Gehrlach et al, 2019; Livneh et al, 2017, 2020).While anatomical studies in diverse species highlight that the insula is one of the most complex anatomical hubs in the mammalian brain The insular cortex (IC or insula) has been suggested to mediate a wide variety of brain functions, such as the processing of external and bodily sensory information 2010), bodily- and self-awareness (Craig, 2009; Craig, 2011), emotion regulation (Etkin, Büchel, & Gross, 2015), feelings and complex social-affective functions like empathy (Damasio & Carvalho, 2013), and switches between large-scale brain networks (Menon & Uddin, 2010). While anatomical studies in diverse species highlight that the insula is one of the most complex anatomical hubs in the mammalian brain We aimed at providing a comprehensive input and output connectivity description of the mouse IC to facilitate the mechanistic investigation of insula functions. We compared the connectivity structure of the IC along its rostro-caudal axis to establish a connectivity-based compartmentalization that may facilitate the comparison across species
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