Axo-axonic cells regulate associative learning.

Abstract

The activity and plasticity of excitatory neurons are regulated in a specific way by local inhibitory neurons. Axo-axonic cells (AACs) are a unique type of inhibitory neurons that primarily form synapses onto the axon initial segment of pyramidal neurons. While their anatomical features have been identified, the functional roles of AACs remain unclear. In this study, we used a specific labeling technique to label AACs in the basolateral amygdala (BLA) and found that they have a crucial role in fear conditioning. By using in vivo calcium imaging of AACs in the BLA, we demonstrated their activation in response to salient stimuli, such as foot shock and reward. Moreover, when AACs were inactivated, the activity of pyramidal neurons increased and fear conditioning was impaired. We discovered that the strength of the inhibitory input from AACs differs between active and non-active neurons during fear conditioning. Additionally, we observed that AACs preferentially receive long-range inputs from the basal forebrain and medial geniculate nucleus. These findings suggest that AACs play a central role in representing salient stimuli and are crucial for regulating BLA activity during memory acquisition.