NPY+ Interneurons in Basolateral Amygdala are Activated by Aversive Stimuli

Traumatic events increase the risk for anxiety disorders, yet knowledge of how trauma modulates neuronal activity to induce anxiety is incomplete. The amygdala, which processes stressful sensory information, is enriched with interneurons that release the anxiolytic neurotransmitter neuropeptide Y (NPY). Amygdala NPY levels are reduced one week after an aversive event, suggesting chronic alteration of NPY+ interneurons; however, studies of in vivo amygdalar NPY+ cell activity during stressors are lacking. Here, we use a genetically encoded calcium sensor together with fiber photometry to investigate in vivo activation of NPY+ cells in basolateral amygdala (BLA) to aversive stimuli in mice. NPY+ cell activation was evaluated in response to two aversive stimuli, air puffs to the face (mild) and footshocks (strong). Air puffs caused a transient elevation of calcium in BLA NPY+ cells, indicating robust neuronal activation, in both male and female mice with no sex-dependent differences. Interestingly, there was habituation of the calcium signal in NPY+ cells to later air puff iterations. Strong footshocks also caused calcium elevation in both male and female mice with no sex-dependent differences. Excitingly, footshock induces a larger calcium response compared to air-puff. In contrast to air puff, the calcium signal to footshock was prolonged in later iterations. BLA NPY+ cell calcium signals were consistent in response to the same footshock protocol delivered 1 week later, indicating that activation of NPY+ cells by footshock is stable across this timeframe. Taken together, these results reveal a potential role for NPY+ interneurons in basolateral amygdala during aversive events.