Potentiation of cholinergic and corticofugal inputs to the lateral amygdala in threat learning

The amygdala, cholinergic basal forebrain, and higher-order auditory cortex (HO-AC) regulate brain-wide plasticity underlying auditory threat learning. Here, we perform multi-regional extracellular recordings and optical measurements of acetylcholine (ACh) release to characterize the development of discriminative plasticity within and between these brain regions as mice acquire and recall auditory threat memories. Spiking responses are potentiated for sounds paired with shock (CS+) in the lateral amygdala (LA) and optogenetically identified corticoamygdalar projection neurons, although not in neighboring HO-AC units. Spike-or optogenetically triggered local field potentials reveal enhanced corticofugal-but not corticopetal-functional coupling between HO-AC and LA during threat memory recall that is correlated with pupil-indexed memory strength. We also note robust sound-evoked ACh release that rapidly potentiates for the CS+ in LA but habituates across sessions in HO-AC. These findings highlight a distributed and cooperative plasticity in LA inputs as mice learn to reappraise neutral stimuli as possible threats.

Automated summary

The amygdala, cholinergic basal forebrain, and higher-order auditory cortex play important roles in brain plasticity during auditory threat learning. This study finds that the response of lateral amygdala and corticoamygdalar projection neurons is enhanced for sounds paired with shock, and there is increased functional coupling between higher-order auditory cortex and amygdala during threat memory recall. These findings provide insights into the neural mechanisms underlying auditory threat learning.