Sympathetic regulatory aspects of cardiac functions are imbedded in the neural circuits of postganglionic sympathetic neurons residing in the stellate ganglia. Postganglionic neuronal subtypes innervating myocardium regulate cardiac functions and remodel myocardium during cardiac pathology. In our previous study, leveraged by viral tracing and scRNAseq revealed cardiac-innervating neuronal subtypes, NA1a enriched in Neuropeptide-Y (NPY) and NA1b is enriched in NPY2r receptor. Therefore, we hypothesized that NPY via NPY2r receptor might interplay a mechanistic role in myocardial remodeling during cardiac-injury related settings. We used C57BL/6J, Npy-ires-Cre, Npy2r-ires-Cre, and Ai32 strains. For chemogenetic experiments, C57BL/6J were injected with plasmids pAAV-hSyn-DIO-mCherry, pAAV-hSyn-hM3D(Gq)-mCherry, and pAAV-hSyn-hM4D(Gi)-mCherry in stellate ganglia. For optogenetic stimulations, Npy+/- and Npy2r+/- mice were crossed with Ai32ChR2(H134R)/EYFP/- and, 8-10 weeks old male were utilized. An optical fiber connected to optic engine was positioned for focal illumination of craniomedial right stellate ganglion stimulation. An electrocardiogram amplified with a differential amplifier was continuously acquired using PowerLab8/35. Heart rate was pumped-up for hM3D(Gq)-mCherry injected (103.53±14.64 bpm, n=3) and were delinquent in hM4D(Gi)-mCherry injected (~76 bpm) in C57BL/6J mice post-CNO (1.0mg/kg body weight) administration compared to either injected saline (0.9%W/V) or inoculated control plasmid pAAV-hSyn-DIO-mCherry in mice and administered either CNO (1.0mg/kg) or saline (0.9%W/V). Npy2r/ ChR2(H134R)/EYFP/- mice showed the highest change in heart rate (79.265±13.46 bpm, n=6) vs. controls (08.89±4.56 bpm, n=4) at 10 Hz stimulation frequency. Our results indicate that Npy2r (Npy-receptors) expressed in NA1b subtypes along with NA1a modulate cardiac sympathoexcitation showing implications being novel targets alone or in combination for sympathetic blockade in cardiac disease.

Sachin Sharma has completed his PhD in cell and molecular biology under the supervision of Professor Israel Hanukoglu and, postdoctoral training at UCLA cardiac arrhythmia center and UCLA neurocardiology center for excellence, David Geffen School of Medicine, University of California Los Angeles, USA. He is currently working as an Assistant Professor of Biotechnology at Graphic Era University, Dehradun. He is currently a member of American Heart Association, Heart Rhythm Society, and editorial team-member of Clinical Neuroscience and Neurosurgery journal.