Home › Physiology › Physiology of the Parasympathetic Nervous System

Physiology of the Parasympathetic Nervous System

Pars parasympathica systematis nervosi autonomici

For medical students2 min readUpdated 2026-10-10

The parasympathetic nervous system (PNS) is a division of the autonomic nervous system responsible for trophotropic functions: relaxation, energy conservation, and baseline metabolism maintenance. Its activity predominates during rest, sleep, and periods of recovery.

Center LocalizationBrainstem (III, VII, IX, X cranial nerves) and the sacral spinal cord.

Main NeurotransmitterAcetylcholine (released at both preganglionic and postganglionic nerve terminals).

Vascular ToneSmooth muscle in most blood vessels lacks parasympathetic innervation.

DurationEffects are extremely short-lived due to the high activity of acetylcholinesterase.

Anatomical Features and Fiber Pathways

The parasympathetic division has a distinct craniosacral localization. The cell bodies of preganglionic neurons lie in two unconnected regions:

Brainstem: Nuclei are located among the motor nuclei of cranial nerves. Fibers from cranial nerves III (oculomotor), VII (facial), and IX (glossopharyngeal) travel to head ganglia, innervating the sphincter pupillae, ciliary muscle, and salivary glands. Fibers of the vagus nerve (n. vagus, X) descend to organs in the thoracic and upper abdominal cavities.
Spinal Cord: Nuclei are located in the gray matter of the sacral spinal cord. Their axons form the pelvic nerves, which innervate the lower abdominal cavity, pelvic organs, and external genitalia.

Parasympathetic nerves consist mainly of long, lightly myelinated preganglionic fibers (Type B) according to the Erlanger-Gasser classification. Ganglia are located directly within the walls of target organs (intramural) or in their immediate vicinity. As a result, unmyelinated postganglionic fibers (Type C) are extremely short. Signal irradiation occurs only at the target organ, making parasympathetic influence strictly localized.

Physiological Effects

The system exerts a global calming effect, promoting anabolic reactions (assimilation) and energy restoration:

Cardiovascular system: Myocardial excitability decreases, heart rate and force decline, and blood pressure drops.
Respiration and thermogenesis: Pulmonary ventilation volume and overall body temperature decrease.
Metabolism: Overall metabolic rate drops. Insulin secretion increases, leading to a decrease in blood glucose levels and active intracellular glycogen storage.
Digestion: Secretory, motor, and absorptive functions of the gastrointestinal tract are simultaneously enhanced.

An important rule: the parasympathetic system does not innervate the smooth muscle of most blood vessels. Exceptions include vessels of the brain, salivary glands, mesentery, and external genitalia.

Synaptic Transmission and Regulation

Excitation transmission in the parasympathetic system occurs faster than in the sympathetic system. The main neurotransmitter at all stages is acetylcholine. The process of its release is triggered by the influx of calcium ions into the presynaptic terminal.

At the postsynaptic membrane of the target organ, acetylcholine binds to muscarinic receptors (mAChRs), activating the enzyme guanylyl cyclase. This converts GTP into the second messenger — cGMP.

The effect of acetylcholine is always discrete. This is because the postsynaptic cleft contains an abundance of the enzyme acetylcholinesterase, which rapidly breaks down the neurotransmitter.

Neurotransmitter release is tightly controlled by presynaptic regulation (feedback mechanisms):

Autoregulation: Accumulated acetylcholine acts on presynaptic M2 receptors, inhibiting further exocytosis.
Cross-inhibition: The sympathetic neurotransmitter (norepinephrine) can bind to presynaptic $\alpha_2$-adrenergic receptors on parasympathetic terminals, also blocking acetylcholine release.

Mnemonic

Sympathetic = 'fight or flight' (ganglia close to the spinal cord, generalized response). Parasympathetic = 'rest and digest' (ganglia directly in the organ, localized response).

Frequently asked questions

Where are the subtypes of muscarinic acetylcholine receptors (M1, M2, M3) localized in various target organs?

Muscarinic receptors have distinct localizations depending on their subtype:

M1 subtype — localized in the stomach on enterochromaffin-like cells; also found on the postsynaptic membrane in parasympathetic transmission pathways.
M2 subtype — present in the heart, mediating the inhibitory influence of the parasympathetic nervous system; also found on the presynaptic membrane, participating in the autoregulation of acetylcholine release.
M3 subtype — the most widespread group: localized in ocular structures (sphincter pupillae, ciliary muscle), smooth muscle of internal organs (bronchi, stomach, intestines, biliary tract, urinary bladder, uterus), exocrine glands (bronchial, gastric, intestinal, salivary, lacrimal, nasopharyngeal, sweat glands, and pancreatic acini), as well as on non-innervated M3 receptors of the vascular endothelium.

What is the ion channel mechanism of bradycardia during vagus nerve stimulation?

During vagal bradycardia, acetylcholine acts on cardiac M2 receptors, which inhibit adenylate cyclase via the Gi-protein pathway, exerting an inhibitory effect on the heart.

At the ionic level in inhibitory synapses of the autonomic nervous system, inhibitory neurotransmitters increase membrane permeability to $K^+$ and $Cl^-$. Potassium ions ($K^+$) leave the cell, and chloride ions ($Cl^-$) enter along their concentration gradient. This results in membrane hyperpolarization, the formation of an inhibitory postsynaptic potential, an increased excitation threshold, decreased excitability, and the blockade of impulse propagation.

Through which autonomic ganglia do the parasympathetic fibers of the oculomotor, facial, and glossopharyngeal nerves pass?

Preganglionic parasympathetic fibers of these cranial nerves travel to the following autonomic ganglia:

Oculomotor nerve (CN III) — fibers run to the ciliary ganglion (ganglion ciliare), from which postganglionic fibers extend to the sphincter pupillae and ciliary muscle.
Facial nerve (CN VII) — fibers travel to the pterygopalatine ganglion (ganglion pterygopalatinum) and submandibular ganglion.
Glossopharyngeal nerve (CN IX) — fibers synapse in the otic ganglion (ganglion oticum), providing innervation to the parotid salivary gland.

Why do parasympathetic effects develop and fade much faster than sympathetic ones?

This is due to enzymatic inactivation. Acetylcholinesterase in synapses breaks down the parasympathetic neurotransmitter (acetylcholine) much faster and more aggressively than MAO and COMT enzymes break down sympathetic norepinephrine.

What is the phenomenon of acetylcholine overflow into the bloodstream?

Normally, acetylcholine is degraded within the synapse. However, if cholinesterase is blocked (e.g., by physostigmine), the neurotransmitter spills into systemic circulation, causing systemic reactions: bradycardia, a drop in blood pressure, and inhibition of GI motility.

How does organ sensitivity change following parasympathetic nerve damage?

According to the Cannon-Rosenblueth law of denervation, structures deprived of innervation become hypersensitive to acetylcholine due to a sharp decrease in the concentration of the degrading enzyme (acetylcholinesterase) in the tissues.

Go deeper

Cannon-Rosenblueth Law of Denervation
Erlanger-Gasser Classification of Nerve Fibers
Second Messengers (GC and cGMP) in Signal Transduction
Interaction Between the ANS and the Endocrine System