Venue : Centre Broca
Cloé L’heraux
Team : Neuronal circuits of associative learning
Neurocentre Magendie
Title :
Contributions of amygdalar basket and axo-axonic cells to aversive states
Abstract :
The survival of animals depends on their ability to detect, assess, and respond effectively to threats. Aversive emotions such as fear and anxiety are essential to these adaptive responses. The basolateral amygdala (BLA) plays a central role in regulating these emotions by integrating danger signals. Within the BLA, excitatory principal neurons (PNs) transmit emotional information, while GABAergic interneurons provide fine control of their activities. Among GABAergic cells, parvalbumin-expressing (PV) interneurons are crucial for regulating anxiety- and fear-related behaviors. Traditionally considered as a homogeneous population, PV interneurons actually comprise distinct types, notably basket cells (BCs), which target the soma of principal neurons, and axo-axonic cells (AACs), which exclusively innervate the axon initial segment, a key site for action potential initiation. This anatomical specificity suggests that BCs and AACs may play complementary roles in modulating emotional states.
This raises a fundamental question: What are the specific contributions of BLA BCs and AACs in shaping aversive emotional states?
In this thesis, we developed a novel transgenic mouse line allowing the selective genetic targeting of BCs and AACs in the BLA. Using this strategy, we recorded their activities in vivo using fiber photometry and selectively inhibited them through optogenetics during anxiety-related and conditioned fear behaviors. Our recordings revealed distinct dynamic activity patterns of AACs and BCs during anxiety-related behaviors. While both BCs and AACs were more active in anxiogenic spaces, AACs were uniquely active during behaviors of high alertness. Optogenetic inhibition of AACs increased avoidance and vigilance behaviors in the elevated plus maze, whereas BC inhibition did not lead to observable behavioral changes. During conditioned fear behaviors, both AACs and BCs were activated in response to aversive stimuli, their predictive cues, and during behavioral expression of fear. However, AACs were particularly active in response to cues, throughout fear conditioning and during memory retrieval, that strongly predicted the aversive stimulus, while BCs showed no specificity. Their selective inhibition during footshock presentations revealed that AACs promote adaptive regulation of fear learning, whereas BCs appeared dispensable during the learning phase. Finally, in vivo electrophysiological recordings allowed us to characterize the direct influence of AACs on PNs in the medial prefrontal cortex. Optogenetic activation of AACs led to a rapid and transient inhibition of activity in a subset of neurons, although overall, effects were limited to a minority of cells, underscoring a sparse influence.
Overall, we found that BCs appear to modulate global BLA networks gain, while AACs exert precise, state-dependent control, shaping anxiety behaviors and fear learning. In conclusion, this work provides the first evidence for distinct contributions of two distinct PV interneuron types in the regulation of aversive emotional states. It sheds new light on the complexity of inhibitory microcircuits in the BLA and opens the way for targeted approaches in understanding maladaptive forms of fear and anxiety-related behaviors.
Key words
Aversive States, Calcium Imaging, Fear Conditioning, Anxiety, Optogenetics, Electrophysiology