LAUSR

Decades of research support the idea that associations between a conditioned stimulus (CS) and an unconditioned stimulus (US) are encoded in the lateral amygdala (LA) during fear learning. However, direct proof for the sources of CS and US information is lacking. Definitive evidence of the LA as the primary site for cue association is also missing. Here, we show that calretinin (Calr)-expressing neurons of the lateral thalamus (Calr + LT neurons) convey the association of fast CS (tone) and US (foot shock) signals upstream from the LA in mice. Calr + LT input shapes a short-latency sensory-evoked activation pattern of the amygdala via both feedforward excitation and inhibition. Optogenetic silencing of Calr + LT input to the LA prevents auditory fear conditioning. Notably, fear conditioning drives plasticity in Calr + LT neurons, which is required for appropriate cue and contextual fear memory retrieval. Collectively, our results demonstrate that Calr + LT neurons provide integrated CS–US representations to the LA that support the formation of aversive memories. The authors describe a thalamic population, innervated by multimodal brainstem inputs, that forms a CS–US association prior to the lateral amygdala. Its fast and plastic signal defines an amygdala activity pattern necessary for adaptive fear learning.