Ca2+ imaging of self and other in medial prefrontal cortex during social dominance interactions in a tube test

Abstract

The study of social dominance interactions between animals offers a window onto the decision-making involved in establishing dominance hierarchies and an opportunity to examine changes in social behavior observed in certain neurogenetic disorders. Competitive social interactions, such as in the widely used tube test, reflect this decision-making. Previous studies have focused on the different patterns of behavior seen in the dominant and submissive animal, neural correlates of effortful behavior believed to mediate the outcome of such encounters, and interbrain correlations of neural activity. Using a rigorous mutual information criterion, we now report that neural responses recorded with endoscopic calcium imaging in the prelimbic zone of the medial prefrontal cortex show unique correlations to specific dominance-related behaviors. Interanimal analyses revealed cell/behavior correlations that are primarily with an animal’s own behavior or with the other animal’s behavior, or the coincident behavior of both animals (such as pushing by one and resisting by the other). The comparison of unique and coincident cells helps to disentangle cell firing that reflects an animal’s own or the other’s specific behavior from situations reflecting conjoint action. These correlates point to a more cognitive rather than a solely behavioral dimension of social interactions that needs to be considered in the design of neurobiological studies of social behavior. These could prove useful in studies of disorders affecting social recognition and social engagement, and the treatment of disorders of social interaction.

Distinct prefrontal projections conversely orchestrate social competition and hierarchy

“…Additionally, we discovered that the mPFC-NAc neurons encode social winning behaviors such as push and resistance, while the mPFC-VTA neurons encode social losing behaviors such as retreat (Figure 3). These results strongly support previous findings that one-third of push-encoding mPFC neurons are also activated when a mouse resists an opponent’s pushes 20 and retreat behavior is encoded in distinct neuronal subpopulations in the mPFC 24,25 . However, a discrepancy exists between our findings and those of previous study.…”

“…However, a discrepancy exists between our findings and those of previous study. Although other researchers have reported that distinct mPFC neurons encode push and approach 24,25 , our findings show that these two behaviors enhance the activity of mPFC-NAc neurons (Figure 3D, E, L, S3A, B, Q). This may be due to the restriction of fiber photometry, which measures the activity of neuronal populations without considering cellular heterogeneity.…”

“…In this study, we discovered that the mPFC-NAc and mPFC-VTA projections play opposing roles in social competition and hierarchy. This provides compelling evidence that distinct neuronal projections in the mPFC encode different social competition behaviors 20,21,24,25,26 . Furthermore, our projection-specific transcriptomic analysis with scRNA-seq data using mPFC projection-specific marker genes 28 and subsequent genetic manipulations uncovered projection-specific molecular determinants for social dominance.…”

“…Modifying the synaptic efficacy or neuronal activity in the mPFC regulates social dominance 20,21,22,23 . Recent studies have revealed that social losing (i.e., retreat) and winning behaviors during the tube test activate distinct mPFC neuronal subpopulations, suggesting that they separately encode opposite aspects of social competition and hierarchy 24,25 .…”

Endocannabinoid signaling regulates post-operative delirium through glutamatergic mediodorsal thalamus-prelimbic prefrontal cortical projection

“…The prefrontal cortex (PFC), a high-order cortex, which plays a vital role in consciousness and cognitive control, is involved in the eCBs associated with recovery from anesthesia (Miller, 2000 ; Miller and Cohen, 2001 ; Zhong et al, 2017 ). Furthermore, the prelimbic prefrontal cortex (PrL), the important part of ventromedial PFC, has been attracting more and more attention in cognition, recognition, learning, and memory (Brockett et al, 2022 ; Cardoso-Cruz et al, 2022 ; Garcia-Font et al, 2022 ). Recent research also showed that increased pro-inflammatory cytokines in the PFC induced by lipopolysaccharide (LPS) led to delirium-like behavior in mice (Zhang et al, 2021 ).…”