NON-INVASIVE ANALYSIS OF THE HEART-BRAIN AXIS IN ZEBRAFISH LARVAE

Cardioception, the monitoring of cardiac function by the nervous system, is a crucial role of the heart-brain axis and has been implicated in emotional processing and affective disorders. Despite its importance, the physiological basis of cardioception remains poorly understood, particularly which parameters of cardiac output are sensed by vagal nodose neurons of the autonomic nervous system (ANS). Zebrafish larvae provide a powerful model for studying cardioception due to their optical transparency and genetic accessibility, enabling non-invasive imaging of cardiac and neuronal activity, as well as optogenetic manipulation of the heart. However, the precise developmental timeline of the zebrafish heart–brain axis remains poorly defined. We show that pharmacological modulation of the ANS already at 4 days post-fertilisation produces the expected changes in heart rate, indicating functional cardiac innervation at this stage. These findings are corroborated by developmental imaging of autonomic cardiac innervation. We further employ optogenetic control of cardiac output as a targeted alternative to pharmacological manipulation. Using this approach, we record activity in nodose neurons following optogenetic cardiac arrest and observe a reduction in neuronal activity proportional to arrest duration. Ongoing work examines how cardiac output manipulation affects behaviour and how cardioceptive signals are processed in distributed, brain-wide circuits. Together, these results establish an all-optical, non-invasive framework for precise manipulation of cardiac output with simultaneous neuronal readout, providing a powerful entry point into the mechanistic study of cardioception and interoception.