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Synapses of the Autonomic Nervous System

For medical students2 min readUpdated 2026-10-10

Autonomic nervous system (ANS) synapses are specialized junctions that mediate impulse transmission between neurons in ganglia, as well as from nerve terminals to effector organs. In pharmacology, they are classically divided into cholinergic and adrenergic based on the neurotransmitter released, which determines drug action profiles.

Preganglionic synapseAcetylcholine is always the neurotransmitter (in both divisions)

Sympathetic (organs)Postganglionic fibers release norepinephrine

Adrenal medullaFunctions as a modified sympathetic ganglion

Pharmacological basisSynapses are classified exclusively by the type of neurotransmitter released

Preganglionic Transmission Level

At the stage of excitation transfer from the preganglionic nerve fiber to the postganglionic neuron, the synaptic mechanism is identical for both the sympathetic and parasympathetic divisions of the autonomic nervous system.

In these autonomic ganglia, the universal chemical transmitter is acetylcholine (ACh). Released from preganglionic terminals, ACh crosses the synaptic cleft and binds to specific receptors on the postganglionic neuron membrane.

Both types of autonomic ganglia contain nicotinic acetylcholine receptors ($N_n$ receptors). In standard neural pathway schematics, this interaction represents parasympathetic ganglia (synapse A) and sympathetic ganglia (synapse B). Thus, during the initial transmission phase from the central nervous system to the periphery, anatomical divisions do not alter the neurochemical nature of the process.

Postganglionic Level and Effector Organs

Key differences in neurochemical transmission emerge at the postganglionic level, specifically at the junction between the nerve terminal and the target effector organ.

Parasympathetic nervous system (Synapse B). Postganglionic parasympathetic fibers continue to use acetylcholine as their neurotransmitter. However, on effector organ cells, ACh interacts with a different receptor subtype—muscarinic acetylcholine receptors ($M$ receptors).
Sympathetic nervous system (Synapse E). Postganglionic sympathetic fibers release a distinct neurotransmitter—norepinephrine (NE). This operates via an adrenergic synaptic mechanism.
Somatic nervous system (Synapse G). For comparison, skeletal muscle innervation involves the somatic nervous system. The neuromuscular junction also uses acetylcholine, but the postsynaptic receptors are specialized skeletal muscle-type nicotinic receptors ($N_m$ receptors).

Unique Innervation of the Adrenal Medulla

The adrenal medulla holds a unique position in autonomic physiology because it functions anatomically and physiologically as a modified sympathetic ganglion. This is due to embryogenesis: chromaffin cells of the adrenal medulla share a common lineage with postganglionic sympathetic neurons.

Innervation is supplied directly by preganglionic fibers, bypassing standard sympathetic ganglia. Transmission here (synapse D) follows the classic ganglionic pattern:

Neurotransmitter: Acetylcholine.
Receptors: Nicotinic $N_n$ receptors located on the chromaffin cell membrane.

Activation of these receptors by ACh triggers massive systemic hormone release into the bloodstream—primarily epinephrine (adrenaline) and norepinephrine (NE).

Pharmacological Classification of Synapses

For clinical pharmacology, categorizing synapses not by anatomical location but strictly by the released neurotransmitter is paramount. This allows for a systematic approach to selecting pharmacotherapy targeting specific receptor subtypes.

Cholinergic synapses (utilizing acetylcholine as the neurotransmitter) include the vast majority of junctions:

Synapses in parasympathetic ganglia.
Synapses in sympathetic ganglia.
Junctions innervating the adrenal medulla.
Somatic neuromuscular junctions (skeletal muscle).
Parasympathetic neuro-effector junctions at target organs.

Adrenergic synapses (utilizing norepinephrine) are represented by a single category: sympathetic neuro-effector junctions at target organs.

Mnemonic

To keep neurotransmitters straight: all «intermediate» relay stations (ganglia and the adrenal medulla) and the entire parasympathetic system run on Acetylcholine. Only the sympathetic system at the very finish line (at the target organ) switches to Norepinephrine.

Frequently asked questions

What types and subtypes of adrenergic receptors are located on effector organ cells?

Postsynaptic membranes of effector cells express $\alpha_1$-, $\beta_1$-, and other adrenergic receptors:

$\alpha_1$-receptors — found in vascular smooth muscle of arteries and veins, the radial dilator muscle of the iris, gastrointestinal and urinary sphincters, the prostatic urethra, the prostate gland, the myometrium, and the splenic capsule.
$\beta_1$-receptors — localized in the heart; stimulation causes tachycardia and increased contractility.
$\beta_2$-receptors — present in bronchial smooth muscle, uterine smooth muscle, and blood vessels of skeletal muscle, mediating relaxation.

Which postganglionic sympathetic fibers are exceptions to the rule and use acetylcholine?

Exceptions include certain postganglionic sympathetic fibers that release acetylcholine instead of norepinephrine. These cholinergic fibers innervate:

Sweat glands — mediate sympathetic sweating (though anatomically sympathetic, they are functionally cholinergic).
Arrector pili muscles — innervate hair piloerectors.
Certain blood vessels — vessels of skeletal muscle (inducing vasodilation for anticipatory oxygen delivery during mobilization).

Acetylcholine release in these vascular beds induces vasodilation.

Which enzyme degrades acetylcholine within the synaptic cleft?

Acetylcholine in the synaptic cleft is broken down by the enzyme acetylcholinesterase. Inhibition of acetylcholinesterase prevents ACh hydrolysis, leading to an accumulation of endogenous acetylcholine in the cleft and potentiation/prolongation of its effects.

What neurotransmitter operates in the ganglia of the autonomic nervous system?

At the preganglionic level in both sympathetic and parasympathetic ganglia, acetylcholine is released. It binds to nicotinic ($N_n$) receptors on the postganglionic neuron.

Why is the adrenal medulla considered part of the sympathetic system?

Chromaffin cells of the adrenal medulla are embryologically related to sympathetic neurons. They are innervated by preganglionic fibers and release epinephrine and norepinephrine into the blood upon $N_n$ receptor stimulation by acetylcholine.

How does signal transmission differ at the neuromuscular junction?

The neuromuscular junction belongs to the somatic nervous system. It also uses acetylcholine, but it binds to specialized skeletal muscle-type nicotinic ($N_m$) receptors.

What principle governs the classification of synapses in pharmacology?

The primary pharmacological criterion is the type of neurotransmitter released. Based on this, synapses are divided into two major groups: cholinergic (acetylcholine) and adrenergic (norepinephrine).

Go deeper

Intracellular signal transduction mechanisms of muscarinic ($M$) receptors
Norepinephrine life cycle: synthesis, storage, release, and reuptake in adrenergic synapses
Differences between adrenergic receptor subtypes ($\alpha_1$, $\beta_1$, $\beta_2$) on effector organs
Structure and function of skeletal muscle-type nicotinic receptors ($N_m$)
The role of chromaffin cells in systemic stress responses