Zahacy, R. | bioRxiv Science

bioRxiv2023

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.

neuroscience↗

bioRxiv2020

Topographic gradients define the projection patterns of the claustrum core and shell in mice

The claustrum is densely connected to the cortex and participates in brain functions such as attention and sleep. Although some studies have reported the widely divergent organization of claustrum projections, others describe parallel claustrocortical connections to different cortical regions. Therefore, the details underlying how claustrum neurons broadcast information to cortical networks remain incompletely understood. Using multicolor retrograde tracing we determined the density, topography, and co-projection pattern of fourteen claustrocortical pathways, in mice. We spatially registered these pathways to a common coordinate space and found that the claustrocortical system is topographically organized as a series of overlapping spatial modules, continuously distributed across the dorsoventral claustrum axis. The claustrum core projects predominantly to frontal-midline cortical regions, whereas the dorsal and ventral shell project to the cortical motor system and temporal lobe, respectively. Anatomically connected cortical regions receive common input from a subset of claustrum neurons shared by neighboring modules, whereas spatially separated regions of cortex are innervated by different claustrum modules. Therefore, each output module exhibits a unique position within the claustrum and overlaps substantially with other modules projecting to functionally related cortical regions. Claustrum inhibitory cells containing parvalbumin, somatostatin, and neuropeptide Y also show unique topographical distributions, suggesting different output modules are controlled by distinct inhibitory circuit motifs. The topographic organization of excitatory and inhibitory cell types may enable parallel claustrum outputs to independently coordinate distinct cortical networks.

neuroscience↗