Bidirectional chemogenetic modulation of claustral activity causes altered cortical dynamics
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Abstract
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.
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used optogenetics to modulate claustrum activity
Do you think using optogenetics would have changed your results? I'm wondering if the duration / pattern of claustral activity dramatically impact how it alters cortical activity. It also makes me curious how different claustral pathways might be differently sensitive to optogenetic vs chemogenetic manipulation. Very cool work!
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When the claustrum was inhibited, seed pixel correlation analysis revealed a profound expansion of areal PFC, indicating that the increased spontaneous activity observed in Figure 1 was synchronized and spatially expansive. Remarkably, expanded local connectivity was similarly observed in adjacent regions including M2 and CG.
It seems like claustrum is regulating both activity levels and connectivity, how related are those changes in this case? Do you think correlations are increasing because of increased activity, or do you think they are separate processes?
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may indicate a parallel control pathway from claustrum
I'm excited by this finding and would love to know if there's a parallel control pathway or if this is due to indirect effects of claustral inhibition. Could you use tracers, or in some other way experimentally determine the answer?
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These increases in activity were significant in the Post CNO recording and most regions returned to near baseline levels at the Post CNO (1.5 hours) recording.
This is a cool finding! Do you think the return to baseline is due to metabolism of CNO, or because of circuit-level adaptation? Do you think there's any significance to the regions that didn't return to baseline?
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