The Role of Respiratory Noradrenergic Neurons Projecting to the Basal Lateral Amygdala in Anxiety‐related Behavior

Abstract

The most commonly reported symptom of panic attacks is respiratory dysfunction, such as hyperventilation. It has been shown that subsets of patients with anxiety disorders show a lower threshold for carbon dioxide level imbalances and exposure to high levels of carbon dioxide (hypercapnia) can induce anxiety‐like behavior such as panic attacks. The false suffocation alarm hypothesis posits that inappropriate activation of respiratory chemoreceptors in response to benign indices triggers an alarm of suffocation danger and may contribute to anxiety and panic disorders. Two potential candidates that may link anxiogenic and respiratory circuitry are the central noradrenergic (NA) system and the amygdala, both of which have been shown to play roles in both breathing and anxiety. Therefore, we hypothesize that projections from the brainstem NA nuclei to the amygdala play a functional role in modulating the hypercapnic ventilatory response and anxiety‐like behavior in mice.To test this hypothesis, we targeted NA projections to the amygdala by using a Cre‐expressing retrograde virus applied to the amygdala of our intersectional DBH‐p2a‐FLPo; RR5, multicolor reporter line to conduct projection mapping of NA neurons to the amygdala and DBH‐p2a‐FLPo; RR1 and RR2 DREADD mice to specifically inhibit or stimulate NA neurons that project to the amygdala. In these mice, we measured respiratory output using whole‐body plethysmography and anxiety‐like behavior using open field, light dark, and elevated plus maze.Preliminary results indicate that DREADD mediated inhibition of NA neurons projecting to the amygdala may result in a decreased hypercapnic ventilatory response. However, upon stimulation of the NA neurons that project to the amygdala, there was no change in the hypercapnic ventilatory response. Inhibition and stimulation of NA neurons projecting to the amygdala result in a possible decrease in anxiety‐like behavior. Our preliminary results demonstrate the feasibility of delineating and accessing NA neurons based on the their projection target and suggest that NA neurons that project to the amygdala may play a role in the hypercapnic ventilatory response, as well as anxiety‐related behavior. Future directions will include the role of amygdala‐projecting NA neurons in behavior, such as fear learning and anxiety‐related behavior, under higher CO2 concentrations.Support or Funding InformationMcNair Medical InstituteR01HL130249R01HL130249‐02S1This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.