Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis

Figure 1.. Simplified illustration of the centres of cardiac neurotransmission, where blue and green lines indicate potentially bidirectional pathways of both efferent and afferent communication. The brainstem (a) comprises the main autonomic centres of the CNS, parts of which may be stimulated through spreading depolarization during an epileptic seizure [14]. Neurons in these centres project via the spinal cord (b) or bilateral vagus nerves (c) to cardiac postganglionic neurons in the ganglia of the sympathetic chain (d) or the intrinsic ganglionated plexi on the heart (e), respectively (reviewed by Ashton et al. [15]). Ganglionated plexi neurons are situated predominately in fat deposits on the surface of the heart (basal pale regions (f)), and they innervate the vasculature and tissues of the specialized conduction system and working myocardium. Painting and art work by M. Cremer.

Figure 2.. (a) Micro co-culture containing a solitary rat sympathetic neuron innervating cardiomyocyte clusters. A single cardiomyocyte cluster is indicated by the arrow at H. The neuron is at 19 days in culture. Inset shows a corresponding action potential recorded from this neuron in response to current injection. Inset scale represents 50 mV (y-axis) and 20 ms (x-axis). (b,c) Reconstruction of the wavefront in a cardiac monolayer. Representative raw image (b) and following background subtraction to reveal waves, a spiral pattern of excitation wavefront is observed (c) from a cardiac monolayer culture using dye-free optical imaging. (a) Reproduced from [68] with permission from Dr Peter R MacLeish, Morehouse School of Medicine, Atlanta, GA, USA, and Dr Paul O'Lague, Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, USA. (b,c) Adapted from [27] with permission from Dr Rebecca Burton and Prof. Gil Bub, University of Oxford.