Mesocorticolimbic circuit mechanisms of social dominance behavior

Abstract

Social animals, including rodents, primates, and humans, partake in competition for finite resources, thereby establishing social hierarchies wherein an individual's social standing influences diverse behaviors. Understanding the neurobiological underpinnings of social dominance is imperative, given its ramifications for health, survival, and reproduction. Social dominance behavior comprises several facets, including social recognition, social decision-making, and actions, indicating the concerted involvement of multiple brain regions in orchestrating this behavior. While extensive research has been dedicated to elucidating the neurobiology of social interaction, recent studies have increasingly delved into adverse social behaviors such as social competition and hierarchy. This review focuses on the latest advancements in comprehending the mechanisms of the mesocorticolimbic circuit governing social dominance, with a specific focus on rodent studies, elucidating the intricate dynamics of social hierarchies and their implications for individual well-being and adaptation.

Fig. 1. The tube test and wet bedding avoidance (WBA) test were used to study social dominance behavior in rodents.

a Schematic illustration of the tube test. b Summary graph for 22 cages of 4 mice with stable ranks measured daily over 6 days. c Schematic illustration of the WBA test. Four cagemate mice competed for an elevated platform in the center of a cage to avoid wet bedding. d Correlation between the amount of time spent on the platform and the rank in the tube test. The images in (c, d) are adapted from Choi et al. with permission.

Fig. 2. Synaptic efficacy in the mPFC bidirectionally regulates social hierarchy.

Excitatory synaptic transmission in the mPFC is greater in social dominants than in subordinates. Synaptic potentiation induced by the expression of Ras or GluA4 in the mPFC increases social hierarchy, whereas social rank is decreased by the expression of Rap or R4Ct in the mPFC. Glutamate and ATP released from astrocytes in the mPFC regulate synaptic efficacy, resulting in changes in social hierarchy. Antisense long noncoding RNA of synapsin II (AtLAS) regulates the expression of synapsin 2b (Syn2b), which binds to AMPA receptors (AMPARs) to inhibit the delivery of AMPARs to synapses, resulting in a reduction in social rank. However, the delivery of AMPARs to synapses by the expression of a membrane-permeable peptide (P-2B) via the fusion of the TAT sequence to the C-terminus of Syn2b disrupts the binding of Syn2b to AMPARs, resulting in an increase in social status. AMPAR trafficking to the synapse by the phosphorylation of Ser818 and Ser831 of the GluA1 subunit is highly correlated with social winning in the tube test.

Fig. 3. Regulation of social dominance behavior by manipulating mesocorticolimbic circuit activities.

Optogenetic activation or chemogenetic inhibition of the mPFC increases or decreases social dominance, respectively. Synaptic potentiation-inducing high-frequency stimulation (HFS) at inputs from the mediodorsal thalamus (MDT) to the mPFC increases social ranks, whereas synaptic depression-inducing low-frequency stimulation (LFS) on MDT-mPFC projection decreases social ranks. The disinhibitory VIP–PV–PYR microcircuit in the mPFC computes information related to social hierarchy. Prefrontal D1- and D2-expressing neurons distinctly regulate social dominance behavior. Optogenetic activation of mPFC neurons projecting to the LH increases winnings during the food competition test. mPFC neuronal populations that project to the NAc or VTA conversely regulate social dominance. Pharmacological inhibition of the NAc decreases social dominance^,. In contrast, D1- and D2-expressing neurons in the NAc regulate social hierarchy. Pharmacological inhibition of the VTA increases social hierarchy^,. Optogenetic activation of VTA neurons expressing dopamine (DA) decreases reward latency during the reward competition test and increases agonistic and aggressive behaviors.