Autonomic Nervous System

Key Points

The autonomic nervous system (ANS) regulates involuntary physiologic functions by integrating afferent sensory input with efferent sympathetic and parasympathetic outputs to maintain cardiovascular, respiratory, and visceral homeostasis.
The sympathetic and parasympathetic divisions differ in functional anatomy: the sympathetic nervous system (SNS) produces diffuse, coordinated responses through high pre-to-postganglionic divergence, whereas the parasympathetic nervous system (PSNS) generates discrete, organ-specific responses due to minimal divergence.
Acetylcholine (ACh) is the universal neurotransmitter at all autonomic ganglia, while postganglionic neurotransmission differs in systems: Norepinephrine (NE) is primarily released by sympathetic postganglionic neurons, and ACh by parasympathetic postganglionic neurons acting on muscarinic receptors.
Autonomic reflex arcs integrate afferent visceral input with efferent autonomic responses that regulate heart rate, vascular tone, and visceral function.

The SNS

The SNS represents the thoracolumbar division of the ANS and originates from the intermediolateral cell columns of T1-T12 and L1-L3.¹

Types of Neurotransmitters

ACh is released from sympathetic preganglionic neurons and binds to nicotinic receptors in autonomic ganglia.
NE is the predominant neurotransmitter released from postganglionic sympathetic neurons.
However, some exceptions include:
- Sympathetic innervation of eccrine sweat glands, where postganglionic fibers release ACh acting on muscarinic receptors.¹
- Sympathetic fibers innervate the renal vasculature, which uses dopamine as its primary neurotransmitter.

Catecholamine Synthesis, Storage, Release, Transmission and Inactivation

Catecholamine synthesis and storage: Catecholamines are synthesized via Tyrosine → DOPA → Dopamine → NE → Epinephrine (EPI), with tyrosine hydroxylase as the rate-limiting step. Dopamine → NE occurs in vesicles via dopamine β-hydroxylase, while NE → EPI is catalyzed by phenylethanolamine-N-methyltransferase in adrenal chromaffin cells.
NE is produced mainly in sympathetic postganglionic neurons, whereas EPI is produced in the adrenal medulla. Catecholamines are stored in vesicles via vesicular monoamine transporter, protecting them from cytoplasmic degradation.

Figure 1. Catecholamine synthesis pathway. Source: Vo C, ChatGPT (OpenAI). Created with AI assistance. Published 2025.

Table 1. Catecholamine synthesis, storage, release, transmission, and inactivation.^1,2
Abbreviations: DOPA, dihydroxyphenylalanine; NE, norepinephrine; EPI, epinephrine; PNMT, phenylethanolamine-N-methyltransferase; VMAT, vesicular monoamine transporter; SNS, sympathetic nervous system; Ca²⁺, calcium ion; α₂, alpha-2 adrenergic receptor; β, beta adrenergic receptor; M₂, muscarinic subtype 2 receptor; MAO, monoamine oxidase; COMT, catechol-O-methyltransferase; TCA, tricyclic antidepressant; VMA; vanillylmandelic acid.

Types of Receptors in the SNS

• Adrenergic and dopaminergic receptors are central to the function of the SNS, mediating the effects of endogenous catecholamines such as NE, epinephrine, and dopamine.

Table 2. Adrenergic and dopaminergic receptors, their location, functions, and systemic effects.1,3,4
Abbreviations: IP3, inositol triphosphate; DAG, diacylglycerol; PLC, phospholipase C; cAMP, cyclic adenosine monophosphate; CNS, central nervous system; CTZ, chemoreceptor trigger zone; SA node, sinoatrial node; AV node, atrioventricular node; SVR, systemic vascular resistance; MAC, minimum alveolar concentration.

The PSNS

The PSNS comprises preganglionic and postganglionic neurons, with preganglionic cell bodies located in the brainstem and in the sacral spinal cord (S2–S4).
Cranial parasympathetic outflow travels through CN III, VII, IX, and X, with the vagus nerve (CN X) providing more than 75% of all PSNS innervation.
Sacral outflow supplies structures not innervated by CN X, including the distal colon, rectum, bladder, uterus, and lower ureters, and plays a key role in pelvic organ emptying and sexual function.

ACh Synthesis, Storage and Transmission

Choline is transported into presynaptic terminals via the choline transporter 1, constituting the rate-limiting step.
Choline acetyltransferase catalyzes the synthesis of ACh from choline and acetyl-CoA.
ACh is packaged into vesicles by the vesicular ACh transporter.
Release is triggered by an action-potential-induced influx of Ca²⁺, causing vesicular fusion via SNARE proteins.
Feedback inhibition is mediated by M2 muscarinic receptors on presynaptic terminals.^1,3

Figure 2. Cholinergic synaptic transmission. An arriving action potential opens voltage-gated Ca²⁺ channels in the presynaptic terminal, and Ca²⁺ influx triggers fusion of ACh-containing vesicles with the presynaptic membrane and release of ACh into the synaptic cleft. ACh binds postsynaptic ACh receptors, opening ligand-gated ion channels and allowing Na⁺ influx to propagate the signal. Signal termination occurs via rapid hydrolysis of ACh by acetylcholinesterase into choline and acetate. Choline is then re-uptaken into the presynaptic terminal, combined with acetyl-CoA, and repackaged into vesicles for reuse. Source: Aboughazala LM et al. Al-Azhar Un. Journal for Research and Studies. 2020.

Muscarinic and Nicotinic Receptors: Subtypes, Location, and Effect

Preganglionic neurons synapse on nicotinic receptors and postganglionic neurons synapse on muscarinic receptors to elicit responses and functions of the PSNS.

Table 3. Nicotinic (NN) receptors and the Muscarinic (M) receptors in the PSNS.¹
Abbreviations: M1, muscarinic subtype 1 receptor; M2, muscarinic subtype 2 receptor; M3, muscarinic subtype 3 receptor G_q G-protein subtype q; G_i G-protein subtype i; NMJ, Neuromuscular Junction.

ANS: Structural and Functional Anatomy¹

ANS governs the involuntary regulation of cardiac, smooth, and glandular activity, coordinating essential visceral functions. It continuously adjusts to changes in somatic motor and sensory activity, thereby enabling visceral reflexes to be triggered in response to external or internal stimuli.
Through this integration, the ANS links the body’s physiological state to emotional and behavioral responses, enabling the anticipation and modulation of responses to stress, disease, and environmental demands.

Central Autonomic Organization^1,4

ANS control is distributed across multiple levels of the central nervous system, with integration occurring along the entire cerebrospinal axis:

Cerebral Cortex: The cerebral cortex provides the highest level of autonomic modulation, particularly in emotionally driven autonomic responses such as vasovagal syncope and stress-induced cardiovascular changes.
Hypothalamus: The hypothalamus serves as the principal integrative center for autonomic regulation, coordinating autonomic, endocrine, and behavioral responses essential for homeostasis.
Medulla and Pons: Brainstem centers within the medulla and pons mediate acute autonomic regulation, including rapid cardiovascular adjustments, maintenance of ventilatory rhythm, and autonomic reflex integration.
Nucleus Tractus Solitarius (NTS): The NTS is the primary sensory nucleus for autonomic afferents, receiving baroreceptor and chemoreceptor input via cranial nerves IX and X. Increased afferent signaling to the NTS inhibits sympathetic vasomotor outflow while enhancing parasympathetic (vagal) activity, resulting in vasodilation and bradycardia.

Figure 3. A map of sympathetic innervation to effectors. Source: Divisions of the Autonomic Nervous System. Anatomy & Physiology. OpenStax College. CC BY 4.0 http://cnx.org/content/col11496/1.6/

Table 4. Differences between the functional anatomy of the PSNS and the SNS.^1,3

ANS Reflexes: Afferent and Efferent Limbs

ANS reflexes follow a consistent pattern: afferent detection leads to central integration, which then produces an efferent autonomic response.^1,3

Afferent Limb: Detects visceral changes such as blood pressure, O₂/CO₂, pH, stretch, osmolarity through cranial nerve IX and X or the spinal nerves; this information is then relayed to either the NTS in the medulla or the hypothalamus.
Central Integration: The medulla modulates cardiovascular and respiratory reflexes. Ganglionic interneurons will regulate excitability through fast excitatory postsynaptic potentials (EPSPs), slow EPSPs, or inhibitory postsynaptic potentials.
Efferent Limb: Preganglionic neurons will release ACh to nicotinic receptors, which will then activate postganglionic neurons in both the SNS and PSNS. Synapsing NE in the SNS (exceptions include the sweat glands and renal vasculature) and ACh in the PSNS. This will affect the effector organs, such as cardiac function, vascular tone, glandular secretion, or smooth muscle activity.

Table 5. Nonexhaustive list of clinically relevant reflexes that modulate autonomic activity^1,5-8

References

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