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MINI-REVIEW

Intrinsic cardiac neurons as the consulate general of the brain in the heart: A review

Meha Fatima Aftab1*
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1 Human Electrophysiology Lab, Dow Institute of Medical Technology, Dow University of Health Sciences, Karachi, Sindh, Pakistan
Brain & Heart, 2901 https://doi.org/10.36922/bh.2901
Submitted: 7 February 2024 | Accepted: 23 April 2024 | Published: 2 May 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Contrary to the prevailing understanding about one-way communication from brain to heart, recent research has unveiled a two-way communication pathway between these two organs, featuring the delivery of signals from the cardiac afferents to the brain. While the medulla oblongata is known to send autonomic signals for cardiac function regulation, 80% of the vagal afferents send signals to the brain for cardiac regulation. The vagus nerve receives these signals from the intrinsic cardiac neurons, often referred to as “the little brain of the heart.” Intrinsic cardiac neurons are neuronal structures with the same biochemical profile as neurons, communicating with the vagus nerve through acetylcholine and expresses markers of neuronal function such as tyrosine hydroxylase and others. Intrinsic cardiac neurons also influence the autonomic system, which can be studied through heart-rate variability measures. Heart rate variability (HRV) is altered in many types of cardiac disorders and is a well-known measure for studying short- and long-term disease-related variations in cardiac function. Some psychiatric disorders such as post-traumatic stress disorder, schizophrenia, and major depression also exhibited alterations in HRV. HRV is related to heartbeat-evoked potentials (HEPs) and electrical potentials in the brain that are influenced by the heart. HEPs are altered in disease states and can be impacted by environmental factors. This paper reviews the existing literature concerning intrinsic cardiac neurons and their possible role in heart-brain communication.

Keywords
Intrinsic cardiac ganglia
Neurocardiology
Heartbeat-evoked potentials
Cardiovascular disease
Psychiatric disorders
Funding
None.
References
  1. Gordan R, Gwathmey JK, Xie LH. Autonomic and endocrine control of cardiovascular function. World J Cardiol. 2015;7(4):204-214. doi: 10.4330/wjc.v7.i4.204

 

  1. Jones GE, Leonberger LT, Rouse CH, Caldwell JA, Jones KR. Preliminary data exploring the presence of an evoked potential associated with cardiac visceral activity. Psychophysiology. 1986;23:445.

 

  1. Armour JA. Intrinsic cardiac neurons. J Cardiovasc Electrophysiol. 1991;2:331-341. doi: 10.1111/j.1540-8167.1991.tb01330.x

 

  1. Lizot G, Pasqualin C, Tissot A, Pagès S, Faivre JF, Chatelier A. Molecular and functional characterization of the mouse intrinsic cardiac nervous system. Heart Rhythm. 2022;19(8):1352-1362. doi: 10.1016/j.hrthm.2022.04.012

 

  1. Luft CD, Bhattacharya J. Aroused with heart: Modulation of heartbeat evoked potential by arousal induction and its oscillatory correlates. Sci Rep. 2015;5:15717. doi: 10.1038/srep15717

 

  1. Fedele L, Brand T. The intrinsic cardiac nervous system and its role in cardiac pacemaking and conduction. J Cardiovasc Dev Dis. 2020;7(4):54. doi: 10.3390/jcdd7040054

 

  1. Keh-Min Liu SI. Topographical and morphological studies of the cardiac Ganglia in the prenatal rat. Showa Univ J Med Sci. 1989;1(1.2):7-22.

 

  1. Horackova M, Slavikova J, Byczko Z. Postnatal development of the rat intrinsic cardiac nervous system: A confocal laser scanning microscopy study in whole-mount atria. Tissue Cell. 2000;32(5):377-88. doi: 10.1054/tice.2000.0126

 

  1. Hildreth V, Webb S, Bradshaw L, Brown NA, Anderson RH, Henderson DJ. Cells migrating from the neural crest contribute to the innervation of the venous pole of the heart. J Anat. 2008;212(1):1-11. doi: 10.1111/j.1469-7580.2007.00833.x

 

  1. Stoyek MR, Croll RP, Smith FM. Intrinsic and extrinsic innervation of the heart in zebrafish (Danio rerio). J Comp Neurol. 2015;523(11):1683-1700. doi: 10.1002/cne.23764

 

  1. Daubner SC, Le T, Wang S. Tyrosine hydroxylase and regulation of dopamine synthesis. Arch Biochem Biophys. 2011;508(1):1-12. doi: 10.1016/j.abb.2010.12.017

 

  1. MacDonald EA, Rose RA, Quinn TA. Neurohumoral control of sinoatrial node activity and heart rate: Insight from experimental models and findings from humans. Front Physiol. 2020;11:170. doi: 10.3389/fphys.2020.00170

 

  1. Accili EA, Redaelli G, DiFrancesco D. Activation of the hyperpolarization-activated current (if) in sino-atrial node myocytes of the rabbit by vasoactive intestinal peptide. Pflugers Arch. 1996;431(5):803-805. doi: 10.1007/BF02253849

 

  1. Huffman WJ, Musselman ED, Pelot NA, Grill WM. Measuring and modeling the effects of vagus nerve stimulation on heart rate and laryngeal muscles. Bioelectron Med. 2023;9(1):3. doi: 10.1186/s42234-023-00107-4

 

  1. Armour JA. Physiology of the intrinsic cardiac nervous system. Heart Rhythm. 2011;8(5):739. doi: 10.1016/j.hrthm.2011.01.033

 

  1. Pickard JMJ, Burke N, Davidson SM, Yellon DM. Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning. Basic Res Cardiol. 2017;112(2):11. doi: 10.1007/s00395-017-0601-x

 

  1. Habecker BA, Anderson ME, Birren SJ, et al. Molecular and cellular neurocardiology: Development, and cellular and molecular adaptations to heart disease. J Physiol. 2016;594(14):3853-3875. doi: 10.1113/JP271840

 

  1. Owji A, Varudkar N, Ebert SN. Therapeutic potential of Pnmt+ primer cells for neuro/myocardial regeneration. Am J Stem Cells. 2013;2(3):137-154.

 

  1. Hoard JL, Hoover DB, Mabe AM, Blakely RD, Feng N, Paolocci N. Cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes, norepinephrine transporters, and the neurotrophin receptors tropomyosin-related kinase A and p75. Neuroscience. 2008;156(1):129-142. doi: 10.1016/j.neuroscience.2008.06.063

 

  1. Steele PA, Gibbins IL, Morris JL, Mayer B. Multiple populations of neuropeptide-containing intrinsic neurons in the guinea-pig heart. Neuroscience. 1994;62(1):241-250. doi: 10.1016/0306-4522(94)90327-1

 

  1. Dehlin HM, Levick SP. Substance P in heart failure: The good and the bad. Int J Cardiol. 2014;170(3):270-277. doi: 10.1016/j.ijcard.2013.11.010

 

  1. Canaider S, Facchin F, Tassinari R, et al. Intracrine endorphinergic systems in modulation of myocardial differentiation. Int J Mol Sci. 2019;20(20):5175. doi: 10.3390/ijms20205175

 

  1. Melendez GC, Li J, Law BA, Janicki JJ, Supowit SC, Levick SP. Substance P induces adverse myocardial remodelling via a mechanism involving cardiac mast cells. Cardiovasc Res. 2011;92(3):420-429. doi: 10.1093/cvr/cvr244

 

  1. Tan CMJ, Green P, Tapoulal N, Lewandowski AJ, Leeson P, Herring N. The role of neuropeptide Y in cardiovascular health and disease. Front Physiol. 2018;9:1281. doi: 10.3389/fphys.2018.01281

 

  1. Chottova Dvorakova M, Mistrova E, Paddenberg R, Kummer W, Slavikova J. Substance P receptor in the rat heart and regulation of its expression in long-term diabetes. Front Physiol. 2018;9:918. doi: 10.3389/fphys.2018.00918

 

  1. Allen E, Coote JH, Grubb BD, et al. Electrophysiological effects of nicotinic and electrical stimulation of intrinsic cardiac ganglia in the absence of extrinsic autonomic nerves in the rabbit heart. Heart Rhythm. 2018;15(11):1698-1707. doi: 10.1016/j.hrthm.2018.05.018

 

  1. Lund DD, Oda RP, Pardini BJ, Schmid PG. Vagus nerve stimulation alters regional acetylcholine turnover in rat heart. Circ Res. 1986;58(3):372-377. doi: 10.1161/01.res.58.3.372

 

  1. McCorry LK. Physiology of the autonomic nervous system. Am J Pharm Educ. 2007;71(4):78. doi: 10.5688/aj710478

 

  1. Duong HTH, Tadesse GA, Nhat PTH, et al. Heart rate variability as an indicator of autonomic nervous system disturbance in tetanus. Am J Trop Med Hyg. 2020;102(2):403-407. doi: 10.4269/ajtmh.19-0720

 

  1. Ferreira M Jr., Zanesco A. Heart rate variability as important approach for assessment autonomic modulation. Motriz Rev Educ Fis. 2016;22(2):3-8. doi: 10.1590/S1980-65742016000200001

 

  1. Randall DC. Towards an understanding of the function of the intrinsic cardiac ganglia. J Physiol. 2000;528(Pt 3):406. doi: 10.1111/j.1469-7793.2000.00406.x

 

  1. Armour JA, Collier K, Kember G, Ardell JL. Differential selectivity of cardiac neurons in separate intrathoracic autonomic ganglia. Am J Physiol. 1998;274(4):R939-R949. doi: 10.1152/ajpregu.1998.274.4.R939

 

  1. Beaumont E, Salavatian S, Marie Southerland E, et al. Network interactions within the canine intrinsic cardiac nervous system: Implications for reflex control of regional cardiac function. J Physiol. 2013;591(18):4515-4533. doi: 10.1113/jphysiol.2013.259382

 

  1. Kim SH, Lim KR, Seo JH, et al. Higher heart rate variability as a predictor of atrial fibrillation in patients with hypertension. Sci Rep. 2022;12(1):3702. doi: 10.1038/s41598-022-07783-3

 

  1. Pokushalov E, Romanov A, Shugayev P, et al. Selective ganglionated plexi ablation for paroxysmal atrial fibrillation. Heart Rhythm. 2009;6(9):1257-1264. doi: 10.1016/j.hrthm.2009.05.018

 

  1. Uther JB, Hunyor SN, Shaw J, Korner PI. Bulbar and suprabulbar control of the cardiovascular autonomic effects during arterial hypoxia in the rabbit. Circ Res. 1970;26(4):491-506. doi: 10.1161/01.res.26.4.491

 

  1. Armour JA. Myocardial ischaemia and the cardiac nervous system. Cardiovasc Res. 1999;41(1):41-54. doi: 10.1016/s0008-6363(98)00252-1

 

  1. Hopkins DA, Macdonald SE, Murphy DA, Armour JA. Pathology of intrinsic cardiac neurons from ischemic human hearts. Anat Rec. 2000;259(4):424-436. doi: 10.1002/1097-0185(20000801)259:4<424:AID-AR60>3.0.CO;2-J

 

  1. Hardwick JC, Southerland EM, Ardell JL. Chronic myocardial infarction induces phenotypic and functional remodeling in the guinea pig cardiac plexus. Am J Physiol Regul Integr Comp Physiol. 2008;295(6):R1926-R1933. doi: 10.1152/ajpregu.90306.2008

 

  1. Hardwick JC, Ryan SE, Beaumont E, Ardell JL, Marie Southerland E. Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction. Auton Neurosci. 2014;181:4-12. doi: 10.1016/j.autneu.2013.10.008

 

  1. Kubota Y, Chen LY, Whitsel EA, Folsom AR. Heart rate variability and lifetime risk of cardiovascular disease: The Atherosclerosis Risk in Communities Study. Ann Epidemiol. 2017;27(10):619-625.e2. doi: 10.1016/j.annepidem.2017.08.024

 

  1. Evans S, Seidman LC, Ci Tsao J, Lung KC, Zeltzer LK, Naliboff BD. Heart rate variability as a biomarker for autonomic nervous system response differences between children with chronic pain and healthy control children. J Pain Res. 2013;6:449-457. doi: 10.2147/JPR.S43849

 

  1. Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health. 2017;5:258. doi: 10.3389/fpubh.2017.00258

 

  1. Tiwari R, Kumar R, Malik S, Raj T, Kumar P. Analysis of heart rate variability and implication of different factors on heart rate variability. Curr Cardiol Rev. 2021;17(5):e160721189770. doi: 10.2174/1573403X16999201231203854

 

  1. McCraty R, Shaffer F. Heart rate variability: New perspectives on physiological mechanisms, assessment of self-regulatory capacity, and health risk. Glob Adv Health Med. 2015;4(1):46-61. doi: 10.7453/gahmj.2014.073

 

  1. Cruciani G, Cavicchioli M, Tanzilli G, Tanzilli A, Lingiardi V, Galli F. Heart rate variability alterations in takotsubo syndrome and related association with psychological factors: A systematic review and meta-analysis. Sci Rep. 2023;13(1):20744. doi: 10.1038/s41598-023-47982-0

 

  1. Evdokimov D, Boldueva SA, Feoktistova VS, Baeva TA. Features of heart rate variability in patients with takotsubo syndrome. Eur Heart J Acute Cardiovasc Care. 2021;10(Suppl 1):zuab020.187. doi: 10.1093/ehjacc/zuab020.187

 

  1. Melillo P, Bracale M, Pecchia L. Nonlinear Heart Rate Variability features for real-life stress detection. Case study: Students under stress due to university examination. Biomed Eng Online. 2011;10:96. doi: 10.1186/1475-925X-10-96

 

  1. Quintana DS, Elstad M, Kaufmann T, et al. Resting-state high-frequency heart rate variability is related to respiratory frequency in individuals with severe mental illness but not healthy controls. Sci Rep. 2016;6:37212. doi: 10.1038/srep37212

 

  1. Rabellino D, D’Andrea W, Siegle G, et al. Neural correlates of heart rate variability in PTSD during sub- and supraliminal processing of trauma-related cues. Hum Brain Mapp. 2017;38(10):4898-4907. doi: 10.1002/hbm.23702

 

  1. Rottenberg J. Cardiac vagal control in depression: A critical analysis. Biol Psychol. 2007;74(2):200-211. doi: 10.1016/j.biopsycho.2005.08.010

 

  1. Kemp AH, Quintana DS, Gray MA, Felmingham KL, Brown K, Gatt JM. Impact of depression and antidepressant treatment on heart rate variability: A review and meta-analysis. Biol Psychiatry. 2010;67(11):1067-1074. doi: 10.1016/j.biopsych.2009.12.012

 

  1. Moon E, Lee SH, Kim DH, Hwang B. Comparative study of heart rate variability in patients with schizophrenia, bipolar disorder, post-traumatic stress disorder, or major depressive disorder. Clin Psychopharmacol Neurosci. 2013;11(3):137-143. doi: 10.9758/cpn.2013.11.3.137

 

  1. Bar KJ, Letzsch A, Jochum T, Wagner G, Greiner W, Sauer H. Loss of efferent vagal activity in acute schizophrenia. J Psychiatr Res. 2005;39(5):519-527. doi: 10.1016/j.jpsychires.2004.12.007

 

  1. Rechlin T, Beck G, Weis M, Kaschka WP. Correlation between plasma clozapine concentration and heart rate variability in schizophrenic patients. Psychopharmacology (Berl). 1998;135(4):338-341. doi: 10.1007/s002130050520

 

  1. Mujica-Parodi LR, Yeragani V, Malaspina D. Nonlinear complexity and spectral analyses of heart rate variability in medicated and unmedicated patients with schizophrenia. Neuropsychobiology. 2005;51(1):10-15. doi: 10.1159/000082850

 

  1. Tessier A, Sibon I, Poli M, Audiffren M, Allard M, Pfeuty M. Resting heart rate predicts depression and cognition early after ischemic stroke: A pilot study. J Stroke Cerebrovasc Dis. 2017;26(10):2435-2441. doi: 10.1016/j.jstrokecerebrovasdis.2017.05.040

 

  1. Chung MS, Yang AC, Lin YC, et al. Association of altered cardiac autonomic function with psychopathology and metabolic profiles in schizophrenia. Psychiatry Res. 2013;210(3):710-715. doi: 10.1016/j.psychres.2013.07.034

 

  1. Chellappa SL, Vujovic N, Williams JS, Scheer FAJL. Impact of circadian disruption on cardiovascular function and disease. Trends Endocrinol Metab. 2019;30(10):767-779. doi: 10.1016/j.tem.2019.07.008

 

  1. Walker WH 2nd, Walton JC, Courtney DeVries A, Nelson RJ. Circadian rhythm disruption and mental health. Transl Psychiatry. 2020;10(1):28. doi: 10.1038/s41398-020-0694-0

 

  1. Jung W, Jang KI, Lee SH. Heart and brain interaction of psychiatric illness: A review focused on heart rate variability, cognitive function, and quantitative electroencephalography. Clin Psychopharmacol Neurosci. 2019;17(4):459-474. doi: 10.9758/cpn.2019.17.4.459

 

  1. Coll MP, Hobson H, Bird G, Murphy J. Systematic review and meta-analysis of the relationship between the heartbeat-evoked potential and interoception. Neurosci Biobehav Rev. 2021;122:190-200. doi: 10.1016/j.neubiorev.2020.12.012

 

  1. Critchley HD, Wiens S, Rotshtein P, Ohman A, Dolan RJ. Neural systems supporting interoceptive awareness. Nat Neurosci. 2004;7(2):189-195. doi: 10.1038/nn1176

 

  1. Schandry R, Montoya P. Event-related brain potentials and the processing of cardiac activity. Biol Psychol. 1996;42(1- 2):75-85. doi: 10.1016/0301-0511(95)05147-3

 

  1. Yuan H, Yan HM, Xu XG, Han F, Yan Q. Effect of heartbeat perception on heartbeat evoked potential waves. Neurosci Bull. 2007;23(6):357-362. doi: 10.1007/s12264-007-0053-7

 

  1. Banellis L, Cruse D. Skipping a beat: Heartbeat-evoked potentials reflect predictions during interoceptive-exteroceptive integration. Cereb Cortex Commun. 2020;1(1):tgaa060. doi: 10.1093/texcom/tgaa060

 

  1. Candia-Rivera D, Machado C. Reduced heartbeat-evoked responses in a near-death case report. J Clin Neurol. 2023;19(6):581-588. doi: 10.3988/jcn.2022.0415

 

  1. MacKinnon S, Gevirtz R, McCraty R, Brown M. Utilizing heartbeat evoked potentials to identify cardiac regulation of vagal afferents during emotion and resonant breathing. Appl Psychophysiol Biofeedback. 2013;38(4):241-255. doi: 10.1007/s10484-013-9226-5

 

  1. Lehrer PM, Gevirtz R. Heart rate variability biofeedback: How and why does it work? Front Psychol. 2014;5:756. doi: 10.3389/fpsyg.2014.00756

 

  1. Amaya Y, Abe T, Kanbara K, Shizuma H, Akiyama Y, Fukunaga M. The effect of aerobic exercise on interoception and cognitive function in healthy university students: A non-randomized controlled trial. BMC Sports Sci Med Rehabil. 2021;13(1):99. doi: 10.1186/s13102-021-00332-x

 

  1. Byun HM, Colicino E, Trevisi L, Fan T, Christiani DC, Baccarelli AA. Effects of air pollution and blood mitochondrial DNA methylation on markers of heart rate variability. J Am Heart Assoc. 2016;5(4):e003218. doi: 10.1161/JAHA.116.003218

 

  1. Jarusevicius G, Rugelis T, McCraty R, Landauskas M, Berškienė K, Vainoras A. Correlation between changes in local earth’s magnetic field and cases of acute myocardial infarction. Int J Environ Res Public Health. 2018;15(3):399. doi: 10.3390/ijerph15030399
Conflict of interest
The author declares that she has no competing interests.
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