A Central Extended Amygdala Circuit That Modulates Anxiety

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• The amygdala and bed nucleus of the stria terminalis (BNST) are implicated in anxiety disorders.
• Circuit and cellular mechanisms underlying anxiety remain largely unknown.

Purpose of the Study:

• To investigate the role of Erbb4 in somatostatin-expressing (SOM+) neurons in anxiety-related behaviors.
• To elucidate the neural circuits and cellular mechanisms connecting the central amygdala (CeA) and BNST in anxiety.

Main Methods:

• Utilized genetic manipulation (Erbb4 gene deficiency in SOM+ neurons) in mice.
• Employed behavioral tests (elevated plus maze, open field test) to assess anxiety.
• Applied electrophysiological, molecular, genetic, and pharmacological techniques to analyze neural circuits.

Main Results:

• Erbb4 deficiency in SOM+ neurons led to heightened anxiety in mice.
• Abnormal anxiety resulted from enhanced excitatory inputs to CeA SOM+ neurons and reduced inhibition of BNST SOM+ neurons.
• Increased dynorphin signaling in CeA SOM+ neurons mediated reduced inhibition of BNST SOM+ neurons.
• Enhanced activity of BNST SOM+ neurons was necessary and sufficient for elevated anxiety.
• Stress in wild-type mice recapitulated the observed anxiety and synaptic dysfunctions.

Conclusions:

• Disruptions in the CeA-BNST circuit, particularly involving SOM+ neurons and dynorphin signaling, contribute to maladaptive anxiety.
• The study identifies novel circuit and cellular mechanisms in the central extended amygdala underlying anxiety.
• Findings suggest potential therapeutic targets for anxiety disorders.