Associative and plastic thalamic signaling to the lateral amygdala controls fear behavior.

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 (CalrLT neurons) convey the association of fast CS (tone) and US (foot shock) signals upstream from the LA in mice. CalrLT input shapes a short-latency sensory-evoked activation pattern of the amygdala via both feedforward excitation and inhibition. Optogenetic silencing of CalrLT input to the LA prevents auditory fear conditioning. Notably, fear conditioning drives plasticity in CalrLT neurons, which is required for appropriate cue and contextual fear memory retrieval. Collectively, our results demonstrate that CalrLT neurons provide integrated CS-US representations to the LA that support the formation of aversive memories.