The amygdala instructs insular feedback for affective learning.

Area of Science:

• Neuroscience
• Computational Neuroscience
• Affective Neuroscience

Background:

• Affective responses rely on assigning value to environmental cues signaling threat or reward.
• This affective value is represented across distributed cortical and subcortical brain regions.
• The functional significance of this hierarchical representation remains largely unknown.

Purpose of the Study:

• To elucidate the neural mechanisms underlying the decomposition of affective value into its components.
• To investigate the cortico-limbic circuitry involved in processing salience and valence.
• To explore the role of interoceptive feedback in affective learning and discrimination.

Main Methods:

• Functional magnetic resonance imaging (fMRI) in mice to map brain activity.
• Optogenetic and chemogenetic techniques to manipulate neural circuit activity.
• Behavioral assays to assess affective learning and conditioned responses.

Main Results:

• A specific cortico-limbic loop involving the insular cortex (IC), central amygdala (CE), and nucleus basalis of Meynert (NBM) was identified.
• The IC integrated unconditioned stimulus (US)-evoked bodily states into conditioned stimulus (CS) valence.
• The CE utilized NBM-mediated bottom-up recruitment of CS representations to encode salience and improve valence discrimination via interoceptive feedback from the IC.
• Disrupting this hierarchical information flow impaired affective learning and conditioned responding.

Conclusions:

• The identified IC↔CE/NBM network decomposes affective value into salience and valence through a hierarchical process involving interoceptive feedback.
• This circuitry is critical for adaptive affective learning and conditioned responding.
• Dysfunction within this network may contribute to intolerance of uncertainty in conditions such as autism spectrum disorder and related psychiatric disorders.