CONTRIBUTIONS OF AMYGDALAR BASKET AND AXO-AXONIC CELLS TO AVERSIVE STATES

The ability to detect and respond appropriately to threats is essential for animal survival and relies on aversive emotional states such as fear and anxiety. The basolateral amygdala (BLA) is a key brain structure involved in these processes, integrating danger-related signals through excitatory principal neurons (PNs) whose activity is tightly regulated by GABAergic interneurons. Among these, parvalbumin-expressing (PV) interneurons are critical for fear- and anxiety-related behaviors. Although often viewed as a uniform population, PV interneurons include distinct subtypes, notably basket cells (BCs), which target PN somata, and axo-axonic cells (AACs), which selectively innervate the axon initial segment, a crucial site for action potential initiation. This anatomical divergence suggests distinct functional roles in emotional regulation.
In this study, we investigated the specific contributions of BCs and AACs in the BLA. We developed transgenic mouse lines enabling selective targeting of these two interneuron types. Using in vivo fiber photometry and optogenetic inhibition during anxiety-related and conditioned fear paradigms, we found that AACs and BCs exhibit distinct activity dynamics. Both cell types were more active in anxiogenic environments, but AACs showed selective activation during states of heightened vigilance. Consistently, optogenetic inhibition of AACs increased avoidance and vigilance behaviors whereas BC inhibition had no detectable effect.
Together, these findings demonstrate that BCs and AACs play distinct roles in aversive emotional processing, with BCs modulating global network gain and AACs providing state-dependent, precise control of anxiety and fear learning.