The Intrinsic cardiac nervous system (ICNS), also known as the heart's "little brain," is a complex network of

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s and

ganglia A ganglion (: ganglia) is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system, this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system, there a ...

embedded within the heart tissue that regulates cardiac function independently of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. It modulates

heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...

conduction Conductor or conduction may refer to: Biology and medicine * Bone conduction, the conduction of sound to the inner ear * Conduction aphasia, a language disorder Mathematics * Conductor (ring theory) * Conductor of an abelian variety * Condu ...

, and cardiac contractility in response to local and external stimuli.

Anatomy

The ICNS consists of clusters of neurons, or ganglia, primarily located in the

atrial The atrium (; : atria) is one of the two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular mitral and tricuspid heart valves. ...

and ventricular walls, with higher concentrations in the

sinoatrial The sinoatrial node (also known as the sinuatrial node, SA node, sinus node or Keith–Flack node) is an oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of cells known as pacemaker cells. The sin ...

(SA) and atrioventricular (AV) nodes. These ganglia contain: * Afferent neurons: Detect mechanical and chemical changes in the heart. *

Efferent neurons Efferent nerve fibers are axons (nerve fibers) of efferent neurons that exit a particular region. These terms have a slightly different meaning in the context of the peripheral nervous system (PNS) and central nervous system (CNS). The efferent ...

: Modulate cardiac muscle activity. *

Interneuron Interneurons (also called internuncial neurons, association neurons, connector neurons, or intermediate neurons) are neurons that are not specifically motor neurons or sensory neurons. Interneurons are the central nodes of neural circuits, enab ...

s: Facilitate communication within the ICNS. * The system is organized into ganglionated plexuses, interconnected by

nerve fibers A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called ...

, forming a

neural network A neural network is a group of interconnected units called neurons that send signals to one another. Neurons can be either biological cells or signal pathways. While individual neurons are simple, many of them together in a network can perfor ...

around the heart. The distribution of ganglia varies across species, with larger

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

s (e.g., humans, dogs) having more extensive networks than smaller mammals (e.g., mice, rats).

Development

The ICNS originates from

neural crest cells The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, an ...

(NCCs) during

embryonic development In developmental biology, animal embryonic development, also known as animal embryogenesis, is the developmental stage of an animal embryo. Embryonic development starts with the fertilization of an egg cell (ovum) by a sperm, sperm cell (spermat ...

: * Sympathetic neurons arise from trunk NCCs migrating along the

dorsal aorta The dorsal aortae are paired (left and right) embryological vessels which progress to form the descending aorta. The paired dorsal aortae arise from aortic arches that in turn arise from the aortic sac. The primary dorsal aorta is located dee ...

. * Parasympathetic neurons derive from vagal NCCs and nodose

placode In embryology, a neurogenic placode is an area of thickening of the epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory nervous system. Placodes are embryonic structures that give rise t ...

s. * Key factors like

bone morphogenetic protein Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Professor Marshall Urist and Professor Hari Reddi discovered their ability to induce the formation of bone and cartilage, BMPs are now ...

s (BMPs), PHOX2B, and HAND2 guide differentiation.

Function

The ICNS integrates sensory information from the heart and coordinates local reflexes. Key functions include: * Heart rate regulation: Adjusts SA node activity in response to stretch or chemical signals. * Conduction modulation: Influences AV node and Purkinje fiber activity for coordinated contraction. * Cardioprotection: Responds to

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

or stress by altering

cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: tha ...

. The ICNS interacts with the

autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...

(ANS), receiving input from sympathetic and

parasympathetic The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The autonomic nervous system is responsible for regulat ...

pathways, but can operate autonomously during disruptions, such as in heart transplants.

Physiology

ICNS neurons release

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

s like

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

, and

neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

s (e.g.,

substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a type of neuropeptide, belonging to the tachykinin family of neuropeptides. It acts as a neurotransmitter and a neuromodulator. Substance P ...

neuropeptide Y Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. It is secreted alongside other neurotransmitters such as GABA and glu ...

vasoactive intestinal peptide Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residue (chemistry), residues that belongs to a Secretin family, glu ...

(VIP)). These mediate local signaling and modulate

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s in cardiac cells, affecting

cardiac action potential Unlike the action potential in skeletal muscle cells, the cardiac action potential is not initiated by nervous activity. Instead, it arises from a group of specialized cells known as pacemaker cells, that have automatic action potential generati ...

s and

contractility Contractility refers to the ability for self- contraction, especially of the muscles or similar active biological tissue *Contractile ring in cytokinesis *Contractile vacuole *Muscle contraction **Myocardial contractility *See contractile cell fo ...

. The system exhibits plasticity, adapting to chronic conditions like

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

Clinical significance

Dysfunction in the ICNS is implicated in

arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

s (

atrial fibrillation Atrial fibrillation (AF, AFib or A-fib) is an Heart arrhythmia, abnormal heart rhythm (arrhythmia) characterized by fibrillation, rapid and irregular beating of the Atrium (heart), atrial chambers of the heart. It often begins as short periods ...

sick sinus syndrome Sinus node dysfunction (SND), also known as sick sinus syndrome (SSS), is a group of abnormal heart rhythms (arrhythmias) usually caused by a malfunction of the sinus node, the heart's primary pacemaker. Tachycardia-bradycardia syndrome is a varia ...

, heart failure, and

sudden cardiac death Cardiac arrest (also known as sudden cardiac arrest ''SCA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly circulate around the body and the blood flow to the brain and other org ...

. Its role in denervated hearts (e.g., post-transplant) highlights its capacity for independent function. Research explores ICNS-targeted therapies, such as

neuromodulation Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a sec ...

, to treat cardiac disorders.

History

The ICNS was first described in the 19th century through

histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

studies of cardiac tissue. Advances in

electrophysiology Electrophysiology (from ee the Electron#Etymology, etymology of "electron" ; and ) is the branch of physiology that studies the electrical properties of biological cell (biology), cells and tissues. It involves measurements of voltage change ...

and

imaging Imaging is the representation or reproduction of an object's form; especially a visual representation (i.e., the formation of an image). Imaging technology is the application of materials and methods to create, preserve, or duplicate images. ...

in the 20th century elucidated its functional role.

References

{{Reflist Cardiac anatomy