Po-01-150 treating cardiac arrhythmias related to autonomic dysfunction: feasibility study of neuromodulation through optogenetic stimulation to light gated ionic pumps in rostral ventrolateral medulla

Sympathetic hyperactivity and poor sleep quality are associated with increased arrhythmia events and cardiovascular mortality. Optogenetic technology is a novel biological technique that uses light to control neurons that have been genetically modified to express light-sensitive ion channels. We aimed to evaluate the modulation of cardiac autonomic activity by optogenetic stimulation of rostral ventrolateral medulla (RVLM) neurons in freely moving rats. Wireless transmission of polysomnographic recording was performed in WKY rats. In group 1 (vehicle control, n=5), the rat was infected by pAAV-CaMKIIa-iRFP. In group 2 (channelrhodopsin 2, ChR2, n=5), the rat was infected by pAAV-CaMKIIa-hChR2(H134R)-iRFP. In group 3 (halorhodopsin, HR, n=5), the rat was infected by pAAV-CaMKIIa-eNpHR3.0-iRFP. Spectral analyses of the electroencephalogram (EEG) and electromyogram (EMG) were evaluated to define active waking (AW), quiet and paradoxical sleeps (QS, PS). Cardiac autonomic activities were measured by analyzing the power spectrum of heart rate variability (HRV). Figure A shows the optic fiber implantation site. In the HRV analysis, we found that the LF/HF ratio and LF significantly increased in channelrhodopsin group during QS stage compared to that in vehicle control group (Fig B and C), respectively. The LF/HF ratio was significantly decreased in halorhodopsin group compared to that in vehicle control group (Fig B). HF ratio was significantly increased in both halorhodopsin and channelrhodopsin groups compared to that in vehicle control group, respectively (Fig D). Optogenetic stimulations of RVLM neurons successfully modulate the cardiac autonomic activity through activating channelrhodopsin and halorhodopsin light-gated ionic pumps. This study provides the feasibility of optogenetic technology as a novel treatment to cardiac arrhythmias related to autonomic dysfunction.