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bioRxiv · 10.1101/2023.08.31.555793

Space wandering in the rodent default mode network

Abstract

The default mode network (DMN) is a large-scale brain network known to be suppressed during a wide range of cognitive tasks. However, our comprehension of its role in naturalistic and unconstrained behaviors has remained elusive because most research on the DMN has been conducted within the restrictive confines of MRI scanners. Here we use multisite GCaMP fiber photometry with simultaneous videography to probe DMN function in awake, freely exploring rats. We examined neural dynamics in three core DMN nodes-- the retrosplenial cortex, cingulate cortex, and prelimbic cortex-- as well as the anterior insula node of the salience network, and their association with the rats spatial exploration behaviors. We found that DMN nodes displayed a hierarchical functional organization during spatial exploration, characterized by stronger coupling with each other than with the anterior insula. Crucially, these DMN nodes encoded the kinematics of spatial exploration, including linear and angular velocity. Additionally, we identified latent brain states that encoded distinct patterns of time-varying exploration behaviors and discovered that higher linear velocity was associated with enhanced DMN activity, heightened synchronization among DMN nodes, and increased anticorrelation between the DMN and anterior insula. Our findings highlight the involvement of the DMN in collectively and dynamically encoding spatial exploration in a real-world setting. Our findings challenge the notion that the DMN is primarily a " task-negative" network disengaged from the external world. By illuminating the DMNs role in naturalistic behaviors, our study underscores the importance of investigating brain network function in ecologically valid contexts. Significance statementOur research advances understanding of the default mode network (DMN), a brain network implicated in numerous neuropsychiatric and neurological disorders. In contrast to previous research examining immobilized subjects, we took the novel approach of investigating DMN function during naturalistic behaviors in freely moving rodents. Using a combination of multisite fiber photometry, video tracking, and computational modeling, we discovered a prominent role for the DMN in naturalistic real-world spatial exploration. Our findings challenge conventional views that the DMN is disengaged from interactions with the external world and underscore the importance of probing brain function in ecologically relevant settings. This work enriches our understanding of brain function and has important implications for pre-clinical investigations of disorders involving DMN dysfunction.

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BibTeXRIS

Nghiem, T.-A. E., Lee, B., Chao, T.-H. H., Branigan, N. K., Mistry, P. K., Shih, Y.-Y. I., Menon, V.. 2023-09-02. Space wandering in the rodent default mode network. https://doi.org/10.1101/2023.08.31.555793

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