The mouse claustrum synaptically connects cortical network motifs

Abstract

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.

Single neurons and networks in the claustrum integrate input from widespread cortical sources

“…Cortical afferents are targeted to CLA neurons based on the projection targets of claustral outputs, further underscoring the existence of a modular claustral network (21,(26)(27)(28). Recently, it has been discovered that cell types in the CLA are responsive to inputs from more than one cortical area, partly contradicting previous reports of unimodal sensory responses in different regions of the CLA of monkeys (29)(30)(31). However, these findings do not address which combinations of cortical inputs converge onto the CLA and onto which CLA neurons.…”