Heterogeneous plasticity of amygdala interneurons in associative learning and extinction

TL;DR

The study shows that inhibitory interneurons in the amygdala play a flexible role in shaping emotional memories through heterogeneous plasticity during learning and extinction.

Contribution

The study reveals that different interneuron subtypes in the amygdala contribute uniquely to emotional memory encoding and extinction through heterogeneous plasticity.

Findings

Amygdala interneurons show complex and heterogeneous plasticity during memory acquisition, expression, and extinction.

VIP-expressing interneurons respond to salient external stimuli, while SST interneurons align with internal behavioral states.

Molecular identity of interneurons biases their functional roles, influencing excitatory neuron activity and plasticity.

Abstract

Neural circuits undergo experience-dependent plasticity to form long-lasting memories, but how inhibitory interneurons contribute to this process remains poorly understood. Using miniature microscope calcium imaging, we monitored the activity of large amygdala interneuron populations in freely moving mice during fear learning and extinction. Here we show that interneurons exhibit complex and heterogeneous plasticity at both single-cell and ensemble levels across memory acquisition, expression, and extinction. Analysis of molecular interneuron subpopulations revealed that disinhibitory vasoactive intestinal peptide (VIP)-expressing cells are predominantly activated by salient external stimuli, whereas the activity of projection neuron targeting somatostatin (SST) interneurons additionally aligns with internal behavioural states. Although responses within each interneuron subtype are non-uniform, molecular identity biases their functional role, producing weighted circuit outputs that can flexibly regulate excitatory projection neuron activity and plasticity. These findings demonstrate that inhibitory interneurons actively shape the encoding and stability of emotional memories, underscoring their importance in adaptive learning.

In this study, the authors uncover how diverse inhibitory interneurons in the amygdala flexibly contribute to fear and safety learning, revealing a key role for inhibition in emotional memory and adaptive circuit plasticity.

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