Neuronal dynamics and functional topology of the rodent default mode network

2416 

Abstract Submission 

Tzu-Hao Chao¹, Byeongwook Lee², LiMing Hsu¹, Domenic Cerri¹, Wei-Ting Zhang¹, Tzu-Wen Wang¹, Srikanth Ryali², Vinod Menon², Yen-Yu Shih¹

¹The University of North Carolina at Chapel Hill, Chapel Hill, NC, ²Stanford University, Palo Alto, CA

Tzu-Hao Chao  
The University of North Carolina at Chapel Hill
Chapel Hill, NC

Byeongwook Lee  
Stanford University
Palo Alto, CA

LiMing Hsu  
The University of North Carolina at Chapel Hill
Chapel Hill, NC

Domenic Cerri  
The University of North Carolina at Chapel Hill
Chapel Hill, NC

Wei-Ting Zhang  
The University of North Carolina at Chapel Hill
Chapel Hill, NC

Tzu-Wen Wang  
The University of North Carolina at Chapel Hill
Chapel Hill, NC

Srikanth Ryali  
Stanford University
Palo Alto, CA

Vinod Menon  
Stanford University
Palo Alto, CA

Yen-Yu Shih  
The University of North Carolina at Chapel Hill
Chapel Hill, NC

Brain imaging studies have shed light on the topology and function of large-scale brain networks. Given the inherent constraints of human studies, rodent models are uniquely positioned for probing the neural basis of DMN dynamics using invasive approaches; however, the translational utility of rodent models is currently limited by an incomplete understanding of rodent DMN. Here, we first examine the synchronization of neuronal activitiy in prelimbic (PrL), cingulate (Cg), retrosplenial (RSC), and anterior insular (AI) cortex in rat DMN during anesthetized resting-state. We then present salient stimuli to awake behaving rats, aiming to functionally characterize roles of putative DMN nodes. Together, these results revealed neuronal activity changes in PrL, Cg, and RSC preceding fMRI-derived DMN activations and cyclical transitions between brain network states. We also demonstrate that salient oddball stimuli suppress PrL, Cg, and RSC and enhance AI neuronal activity. These findings elucidate the neurophysiological foundations of rodent DMN, its spatiotemporal dynamical properties, paving the way for future translational studies [1]. Further, we simultaneously imaged two awake mice during spontaneous social behavior and observed robust synchronization in key DMN region. These techniques offer compelling advantages for future efforts mapping functional brain networks.

We concurrently measured neuronal calcium activity in the RSC, Cg, PrL, and AI of Thy1-GCaMP6f transgenic rats with an MR-compatible, 4-channel, fiber photometry platform (Fig. 1A). We used our platform and computational modeling to characterize DMN and AI neuronal dynamics under resting-state and awake, salient stimuli conditions. We further developed a silent fMRI method named Steady-state On-the-Ramp Detection of INduction-decay signal with Oversampling (SORDINO) for hyperscanning study between two awake face-to-face mice.

We found: 1) robust neuronal resting-state connectivity between RSC, Cg, and PrL (Fig. 1B, C); 2) specific patterns of neuronal activity in the AI and the RSC, Cg, and PrL in relation to fMRI-derived DMN activation and deactivation peaks (Fig. 1D, E); 3) significant neuronal inhibitory causal outflow from AI to RSC, Cg, and PrL during resting-state condition (Fig. 2A, B); 4) cyclical state transitions characterized by neuronal activity in AI being intermittently in and out of phase with activity of RSC, Cg, and PrL during resting-state condition (Fig. 2C-E); 5) salient stimulus–induced activation of AI and deactivation of RSC, Cg, and PrL in free-moving rats (Fig. 2F, G); and 6) PrL synchronization across two face-to-face mouse brains during social interaction (Fig. 2H-K), whereas S1 showed no synchronization between the two mouse brains (Fig. 2L-N).

Our results provide neuronal activity evidence that RSC, Cg, and PrL function as DMN nodes in rodent brain, with RSC and Cg showing the closest correspondence in their dynamics and PrL exhibiting a potentially dual-purpose role at the interface between DMN and SN. Our results also reveal a neuronal basis of causal inhibitory control from AI to RSC that facilitate access to attentional resources as observed in fMRI studies. These findings identify a translational and neural correspondence between AI and DMN responses in rats to salient task-relevant stimuli and show that rodent AI plays a causal role in DMN-SN dynamic switching. Our proof-of-concept hyperscanning study further corroborates the findings by showing PrL synchronization across two face-to-face mice, in agreement with human studies showing synchronized DMN during social interaction [2-4]. Together, our study paves the way for future translational studies using rodent models to investigate cellular basis of cognitive control circuits, which can help understand the dynamic properties of brain states, define their relationship to behaviors, and ultimately design network-based treatment regimens for neuropsychiatric and neurological disorders.

Social Interaction

Anatomy and Functional Systems ²

Multi-Modal Imaging ¹

Perception and Attention Other

FUNCTIONAL MRI

Limbic Systems

Modeling

OPTICAL

Social Interactions

Other - Fiber photometry; Default mode network; Salience network