Bidirectional chemogenetic modulation of claustral activity causes altered cortical dynamics

In recent years, there has been a growing interest in understanding the function of the claustrum. The claustrum is a thin, long, subcortical structure with dense connections to the cortex. Despite these extensive connections, the manner in which the claustrum influences broader cortical activity remains unclear. We used mesoscale calcium fluorescence imaging to examine resting state cortical activity (1-5Hz) and sensory-evoked responses in lightly anesthetized mice, before and after bi-directional chemogenetic modulation of claustrum-prefrontal neurons. Claustrum inhibition resulted in increased activity in anterior-medial cortical areas, whereas claustrum excitation resulted in decreased activity in anterior-medial cortical regions. Claustrum inhibition also led to an increased local coupling between areas of frontal cortex, a decreased correlation between anterior medial regions-of-interest (ROIs) and lateral and posterior ROIs, and an increased sensory evoked response in the visual cortex. These results are consistent with the finding that the claustrum has a large feed-forward inhibitory effect on the PFC, and the concept that specific claustrocortical pathways may modulate recruit and synchronize activity in topographically distinct cortical modules. Together these results show that neural activity in the claustrum modulates the excitability of prefrontal cortical networks, suggesting a potential target for prefrontal-dependent behaviors such as learning, attention, and stress regulation.