journal club

Amygdala interneuron subtypes control fear learning through disinhibition (Asim Rashid)

AUTHORS: Steffen B. E. Wolff, Jan Grundemann, Philip Tovote, Sabine Krabbe, Gilad A. Jacobson, Christian Muller, Cyril Herry, Ingrid Ehrlich, Rainer W. Friedrich, Johannes J. Letzkus & Andreas Luthi

ABSTRACT: 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, PV1 interneurons are excited and indirectly disinhibit the dendrites of basolateral amygdala principal neurons via SOM1 interneurons, thereby enhancing auditory responses and promoting cue–shock associations. During an aversive footshock, however, both PV1and SOM1 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.