Over the past few decades, research involving the neural control of breathing has centered on how the breathing rhythm is generated and how sensory systems detect internal and external changes to modulate the breathing pattern. While we have learned that the regulatory breathing rhythm originates in the medulla, we know little about the neural circuits by which breathing affects emotional state. The positive effects of controlled breathing on emotional state have been observed across many contexts and in the clinic. Using objective behavioral, physiological, and neuroanatomical parameters, we propose: i) to fully determine the neural pathways in mice from the preBötzinger Complex, the key site generating inspiratory rhythm in the medulla, to supramedullary regions, in particular to the locus coeruleus and its ascending projections, that effect and/or affect emotional state, and; ii) to establish the role of these projections from the preBötzinger Complex in mediating the effects of breathing on anxiety, fear and panic in mice. The proposed research has the potential to lead to more effective methods for treating debilitating negative emotional states

In humans, continuous breathing from birth is essential to life and requires that the nervous system generate a reliable and robust rhythm that drives inspiratory and expiratory muscles. The proposed studies will significantly advance our understanding of how controlled breathing can produce positive effects on emotional state for amelioration of anxiety, fear, and panic.