Mark Fishman

The heart, like all internal organs, has its own local mini-brain. Nerve cells designed to sense the microenvironment connect to other neurons and to heart muscle and to pacemaker cells. This circuit sends signals to the brain and, in turn, is regulated by central nervous system control. It is brought into play for normal blood pressure and oxygen level control and for flight-or-fight responses, adaptation to low oxygen environments, and for “playing dead”, all evolutionary strategies conserved from fish to man. When the system falters, as in disorders termed dysautonomia, the consequences for patients are dire, including syncope and arrhythmias.   Our goal is to understand the complete circuitry and the function of each individual nerve cell. What signals do they register? How do cardiac nerves set the “internal state” of the brain and its responsiveness to external stimuli? How does the system interact with respiration and adapt to stressors such as hypoxia?   We use the zebrafish for these projects. Collaboratively with the labs of Florian Engert (MCB) and of Misha Ahrens at Janelia, we are defining the connectivity of nerve cells in the heart and associated ganglia, and the central nervous system centers to which they connect. Projects involve single cell transcriptional analysis, electron microscopy, expansion microscopy, and optogenetics, the latter to test and reveal function of individual cells.