Amygdalar Plasticity in Airway Disease

Asthma is one of the most common immunological diseases among humans. Chronic airway inflammation drives asthma pathophysiology. While much effort has focused on understanding the airway intrinsic effects of inflammation, chronic inflammation also activates stress‐responsive brain regions, including the amygdala. This is important because greater amygdala activity exaggerates inflammatory responses, and greater amygdala activation in asthmatic patients correlates with reduced bronchodilator responses. Within the amygdala, pyramidal neurons of the basolateral amygdala (BLA) encode aversive stimuli. These neurons are characterized by spiny dendrites, are excitatory (e.g., glutamatergic), and exhibit unique cellular and structural plasticity in response to aversive stimuli that is mechanistically linked to BLA function. Thus, pyramidal neurons might be key targets of inflammation that further drive asthma pathology. Here we test the central hypothesis that pyramidal neurons of the BLA encode airway inflammation and exacerbate asthma pathophysiology. Our preliminary data suggest that an acute asthma exacerbation increases activity of the murine BLA, as evidenced by c‐fos expression and manganese‐enhanced MRI. Further, we show that global pharmacological disruption of glutamatergic signaling mitigates airway disease features, including airway hyperreactivity and mucus hypersecretion. Finally, we show that airway inflammation increases dendritic spine density in pyramidal neurons of the BLA. These results identify novel therapeutic targets for asthma, and possibly other airway diseases.