Amygdala interneuron subtypes control fear learning through disinhibition

Learning is mediated by experience-dependent plasticity in neuronal circuits. Activity in neuronal circuits is tightly regulated by different subtypes of inhibitory interneurons, yet their role in learning is poorly understood. Using a combination of in vivo single-unit recordings and optogenetic manipulations, we show that in the mouse basolateral amygdala, interneurons expressing parvalbumin (PV) and somatostatin (SOM) bidirectionally control the acquisition of fear conditioning-a simple form of associative learning-through two distinct disinhibitory mechanisms. During an auditory cue, PV+ interneurons are excited and indirectly disinhibit the dendrites of basolateral amygdala principal neurons via SOM+ interneurons, thereby enhancing auditory responses and promoting cue-shock associations. During an aversive footshock, however, both PV+ and SOM+ interneurons are inhibited, which boosts postsynaptic footshock responses and gates learning. These results demonstrate that associative learning is dynamically regulated by the stimulus-specific activation of distinct disinhibitory microcircuits through precise interactions between different subtypes of local interneurons.