Molecular and neural control of social hierarchy by a forebrain-thalamocortical circuit

DOI: 10.1016/j.cell.2025.07.024

Abstract

Many animal groups are organized hierarchically, which generates behavioral states that facilitate social interactions. Although generally stable, social status can change, underscoring the plasticity of underlying neural circuits. We examined competition among unfamiliar male mice and uncovered how the molecular and biophysical characteristics of a forebrain-thalamocortical circuit affect hierarchy. We identify the mediodorsal thalamus (MDT) as a hub receiving inputs from the orbitofrontal cortex and basal forebrain and projecting to the caudal anterior cingulate cortex (cACC) to regulate competitive performance. This circuit becomes potentiated or depressed in high- and low-rank males, respectively, in part through altered expression of the voltage-gated ion channel Trpm3 and synaptic plasticity. In high-rank mice, MDT projections drive inhibition of cACC pyramidal cells, promoting winning, in a pattern strikingly opposite to the dorsomedial prefrontal cortex, where winners display increased pyramidal cell activity. Our data suggest a model in which hierarchy modulation relies on coordinated remodeling of multiple forebrain-thalamocortical circuits.