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Learning a threat converges on the circuit processing innate threat

Mermet-Joret, N.; Nazari, M.; Pommer, A. T.; Ansarifar, S.; Silva Luz, J.; Vestergaard, A.-K.; Nabavi, S.

2026-08-31 neuroscience
10.64898/2026.08.26.747219 bioRxiv
Show abstract

A prevailing view in affective neuroscience holds that innate and learned behaviors are processed through distinct neuroanatomical pathways, one pre-wired, the other running on synaptic plasticity. However, here we show that processing innate and learned threats in the lateral amygdala deviates fundamentally from this view. We tracked the three core elements of circuit function (excitatory neurons, inhibitory neurons, and neuromodulators) in mice, as they were exposed to an innately aversive looming stimulus and as they learned a cued threat. Tracking the same neurons across sessions, revealed a subpopulation of excitatory neurons recruited by the innate threat that was preferentially potentiated following auditory threat learning. Furthermore, both forms of threat converged on the same modulatory mechanisms: the disinhibitory VIP/SST motif and norepinephrine release, but with a critical difference. While the innately aversive stimulus possessed privileged access to these pathways, the learned cue acquired access through synaptic plasticity. In this instance, learning about a new threat apparently recruits a circuit that protects animals from natural threats.

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