Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

Abstract

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.

Electrical properties and synaptic transmission in mouse intracardiac ganglion neurons in situ

“…Mechanical disruption or pharmacological blockade of parasympathetic innervation has been reported to shorten ventricular refractory periods and increase the incidence of ventricular arrhythmia in murine hearts (Herring et al, 2019;Jungen et al, 2017). Many studies, using diverse recording techniques, species, and levels of cellular organization have considered the properties of mammalian intrinsic cardiac ganglion neurons (Ashton et al, 2018).…”

Enhanced atrial internal-external neural remodeling facilitates atrial fibrillation in the chronic obstructive sleep apnea model

“…These conclusions are in accord with previous clinical study studies indicating that LF and the LF/HF ratio were both upregulated in OSA patients [ 28 ]. Previous clinical and basic studies had confirmed that sympathetic hyperactivity was closely related to AF inducibility [ 30 – 32 ]. Similarly, in our study, we found that HRV variation was consistent with atrial electrophysiological changes.…”

The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction

“…Moreover, the stimulation of GP in the left atrial fat pad lowers the threshold for atrial fibrillation, whilst their ablation can prevent it [ 199 , 200 ]. However, because of the intricated GP network, their role in physiological regulation of the CCS, innervation, and modulation of ventricles, ablation procedures can have serious side-effects, among them ventricular fibrillation [ 209 ]. Furthermore, neuronal remodeling (e.g., an increased presence of sympathetic neurons) has been reported in atrial fibrillation, which could have an effect on the outcome of ablation therapy [ 7 ].…”