Projection-defined amygdala neurons encode emotional memory through distinct transcriptomic programs

Summary

The amygdala is crucial for emotional memory, but the molecular programs that enable its distinct circuits to encode different memory features remain unclear. Combining single-cell RNA sequencing with retrograde tracing, we investigated transcriptomic dynamics of amygdala neurons projecting to nucleus accumbens (NAc) or auditory/temporal association cortex (AuC/TeA) during formation and long-term retention of fear and reward memories. We found that memory engages pathway-specific transcriptional programs of synaptic genes determined by valence, temporal stage, and projection target. Notably, the AMY→AuC/TeA pathway, previously considered a fear circuit, showed robust modulation during reward memory retention, and chemogenetic silencing confirmed its essential role in reward memory. Projection-defined neurons are transcriptionally and functionally heterogeneous: some subpopulations encode a single feature of emotional memory, such as an AMY→NAc subpopulation for reward memory formation and retention, and an AMY→AuC/TeA subpopulation for retention of fear and reward memories. Most subpopulations, however, encode multiple features via largely non-overlapping gene programs. We further identified Dcn as a selective marker for an AMY→NAc subpopulation preferentially recruited during fear memory formation. Our findings reveal a principle of projection-, valence-, and time-dependent transcriptional programming, demonstrate how subpopulations multiplex memory features via dynamic gene networks, and provide a comprehensive resource for dissecting amygdala function.

Details

Organism

Mus musculus

Samples

15 samples

Publication Date

Jan 19, 2026

Platform

24247

Entry Type

GSE

Identifier