A Distinct Metabolically Defined Central Nucleus Circuit Bidirectionally Controls Anxiety-Related Behaviors

Area of Science:

• Neuroscience
• Molecular Biology
• Psychiatry

Background:

• Anxiety disorders affect a significant portion of the global population.
• The central nucleus of the amygdala (CeA) is implicated in anxiety, but its molecular and circuit mechanisms are unclear.
• Soluble epoxide hydrolase (sEH) plays a role in psychiatric disorders and metabolizes polyunsaturated fatty acids.

Purpose of the Study:

• To investigate the role of sEH in CeA neurons in regulating anxiety-related behaviors.
• To elucidate the molecular and circuit mechanisms by which sEH in the CeA influences anxiety.

Main Methods:

• Investigated sEH expression in the CeA of adult male mice.
• Utilized genetic deletion of sEH in CeA neurons and astrocytes.
• Employed chemogenetics and optogenetics to manipulate sEH-expressing CeA neurons and their projections to the bed nucleus of the stria terminalis (BNST).

Main Results:

• sEH is enriched in CeA neurons and its deletion in these neurons induces anxiety-like behaviors.
• sEH is essential for maintaining the excitability of sEH-expressing CeA neurons (sEH^CeA neurons).
• sEH^CeA neurons directly project to the BNST (sEH^CeA-BNST pathway), and manipulating this pathway bidirectionally affects anxiety-related behaviors.

Conclusions:

• sEH in CeA neurons is a critical regulator of anxiety-related behaviors.
• The sEH^CeA-BNST neural pathway is a key circuit involved in the modulation of anxiety.
• These findings reveal novel molecular and circuit mechanisms underlying anxiety.