Deconstructing the neural circuit underlying social hierarchy in mice

Area of Science:

• Neuroscience
• Animal Behavior
• Social Hierarchy

Background:

• Social competition establishes hierarchical status, impacting animal health and behavior.
• The dorsomedial prefrontal cortex (dmPFC) is crucial for regulating social competition.
• The specific downstream neural circuits controlled by the dmPFC for win/lose behaviors were not well understood.

Purpose of the Study:

• To identify and characterize the distinct neural pathways downstream of the dmPFC that regulate social competition.
• To elucidate how the dmPFC orchestrates win- and lose-related behaviors through top-down control.

Main Methods:

• Whole-brain c-Fos mapping to identify active neurons.
• Fiber photometry to monitor neural activity in vivo.
• Optogenetics and chemogenetics for targeted neuronal manipulation.
• In vivo and in vitro electrophysiology recordings.

Main Results:

• Identified anatomically segregated neural pathways downstream of the dmPFC.
• dmPFC layer 5 neurons projecting to the dorsal raphe nucleus (DRN) and periaqueductal gray (PAG) promote competition.
• dmPFC layer 2/3 neurons projecting to the anterior basolateral amygdala (aBLA) suppress competition.
• Opposing activity changes in these pathways during competition and inhibitory interaction between them.

Conclusions:

• The dmPFC utilizes distinct, anatomically segregated pathways to promote and suppress social competition.
• An antagonistic interplay between win-promoting and lose-suppressing pathways is a central principle of dmPFC control over social behavior.
• This top-down control mechanism is critical for orchestrating complex social behaviors.