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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE316516 | GEO | 2026/01/19

REPOSITORIES: GEO