RT Journal Article SR Electronic T1 The mouse claustrum synaptically connects cortical network motifs JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.03.31.486634 DO 10.1101/2022.03.31.486634 A1 Houman Qadir A1 Brent W. Stewart A1 Jonathan W. VanRyzin A1 Qiong Wu A1 Shuo Chen A1 David A. Seminowicz A1 Brian N. Mathur YR 2022 UL http://biorxiv.org/content/early/2022/04/01/2022.03.31.486634.abstract AB Spatially distant areas of cerebral cortex coordinate their activity into networks that are integral to cognitive processing. A common structural motif of cortical networks is co-activated frontal and posterior cortical regions. Knowledge of the neural circuit mechanisms underlying such widespread inter-areal cortical coordination is lacking. Using anesthetized mouse functional magnetic resonance imaging (fMRI) we discovered that mouse frontal cortical functional connectivity reflects the common cortical network motif in its functional connectivity to posterior cortices, but also demonstrates significant functional connectivity with the claustrum. Exploring whether the claustrum may synaptically support such network architecture, we used a channelrhodopsin-assisted electrophysiological circuit mapping approach to assess the strength of synaptic connectivity of 35 unique frontal cortico-claustral-cortical connections through 1,050 subtype-identified claustrum projection neurons. We observed significant trans-claustral synaptic connectivity from the anterior cingulate cortex and prelimbic prefrontal cortex back to originating frontal cortical regions as well as to posteriorly-lying visual and parietal association cortices contralaterally. The infralimbic prefrontal cortex possessed significant trans-claustral synaptic connectivity with the posteriorly-lying retrosplenial cortex, but to a far lesser degree with visual and parietal association cortices. These data reveal discrete extended cortical pathways through the claustrum that are positioned to support cortical network motifs central to cognitive control functions.Competing Interest StatementThe authors have declared no competing interest.