Molecular and Functional Taxonomy of Cardiovagal Neurons

PROJECT SUMMARY Heart rate is one of the most widely used and informative metrics of health. Yet, the neural circuits which determine heart rate are only partly known. Over a century of research has shown that heart rate is oppositely controlled by the two branches of the autonomic nervous system, which increase (sympathetic) or decrease

(parasympathetic) heart rate in response to the body’s changing needs for circulation. Parasympathetic input to the heart occurs through the vagus nerve, a cranial nerve which carries axons from hindbrain parasympathetic neurons, known as cardiovagal neurons, to downstream neurons in the cardiac ganglia. A minority of these

neurons reside in a region of the hindbrain called the dorsal motor nucleus of the vagus (DMV) but were recently found capable of robustly decreasing heart rate. However, the DMV is also home to a variety of other neurons, which presents significant technical challenges to studying the cardiovagal subset. For instance,

intermingled with the DMV cardiovagal neurons are parasympathetic neurons which mediate digestive, metabolic, and immune functions. The inability to access the cardiovagal subset has greatly limited what we know about their synaptic circuitry, gene expression, and specific roles in heart function. Thus, there is much to

learn about the nature of these important neurons, how they function, and how they can be targeted to treat heart disease. Our preliminary studies identified one molecular subtype of DMV neuron which innervates cardiac ganglia. Our proposed research will target this subtype to manipulate its activity and reveal its

physiological role and significance. The results will identify DMV neurons which control heart rate and so may reveal a new therapeutic target for treating heart disease.