OPTOGENETIC CONTROL OF INTRACARDIAC NEURONS MODULATES HEART RATE IN FREELY MOVING MICE

Mental and cardiovascular health are closely linked, as evidenced by numerous clinical studies reporting elevated heart disease risk in patients suffering from depression or anxiety disorders, and vice-versa. The autonomic nervous system serves as a key bidirectional communication pathway between the heart and the brain. Yet, little is known about the circuit mechanisms underlying heart-brain communication and how cardiac feedback to the brain, a process termed interoception, influences affective behavioral states. This is in part due to the lack of sufficiently precise perturbation methods to study complex inter-organ communication.
We present a novel approach to modulate heart rate in freely moving mice through optogenetic activation of intracardiac neurons. Using systemic delivery of a viral vector with peripheral nervous system tropism in a Cre-transgenic mouse line, we achieved selective expression of the red-light sensitive opsin ChRmine in cardiac cholinergic neurons. To illuminate the right atrium - where postganglionic parasympathetic neurons are predominantly located - we employed an implantable wireless µLED device. Optical stimulation of ChRmine-expressing cardiac neurons in freely behaving mice led to a decrease in heart rate, consistent with increased parasympathetic drive and demonstrating functional control of cardiac activity via optogenetics.
This work opens up new possibilities for optogenetic modulation of cardiac function in vivo, a stepping-stone to study the causal influence of heart dynamics and interoceptive processes on brain function and behavior.