Synaptic plasticity in cardiac innervation and its potential role in atrial fibrillation

Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or "little brains," can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation

Application of micro-computed tomography with iodine staining to cardiac imaging, segmentation, and computational model development

Micro-computed tomography (micro-CT) has been widely used to generate high-resolution 3D tissue images from small animals non-destructively, especially for mineralized skeletal tissues. However, its application to the analysis of soft cardiovascular tissues has been limited by poor inter-tissue contrast. Recent ex vivo studies have shown that contrast between muscular and connective tissue in micro-CT images can be enhanced by staining with iodine. In the present study, we apply this novel technique for imaging of cardiovascular structures in canine hearts. We optimize the method to obtain high resolution X-ray micro-CT images of the canine atria and its distinctive regions - including the Bachmann’s bundle, atrioventricular node, pulmonary arteries and veins - with clear inter-tissue contrast. The imaging results are used to reconstruct and segment the detailed 3D geometry of the atria. Structure tensor analysis shows that the arrangement of atrial fibres can also be characterised using the enhanced micro-CT images, as iodine preferentially accumulates within the muscular fibres rather than in connective tissues. This novel technique can be particularly useful in non-destructive imaging of 3D cardiac architectures from large animals and humans, due to the combination of relatively high speed (~1 hour/scan of a large canine heart) and high voxel resolution (36 μm) provided. In summary, contrast micro-CT facilitates fast and non-destructive imaging and segmenting of detailed 3D cardiovascular geometries, as well as measuring fibre orientation, which are crucial in constructing biophysically detailed computational cardiac models