Learning Objective: Learners will be able to describe the organization of the peripheral nervous system, compare neurotransmitters and receptors used in motor, sympathetic, and parasympathetic pathways, and relate these mechanisms to clinically relevant signs and pharmacological principles.

The PNS consists of all neural structures outside the CNS and mediates motor control, visceral regulation, and autonomic reflexes. It includes:

Somatic Motor System
Autonomic Nervous System (ANS)
- Parasympathetic Division
- Sympathetic Division

Each division uses distinct neurotransmitters, receptors, and physiological pathways.

Somatic Motor System

Motor Neurons

Alpha-motor neurons release ACh at the neuromuscular junction (NMJ).
ACh binds to nicotinic muscle (NM) receptors.
These neurons are large and heavily myelinated → very fast conduction speeds.
Effect: Direct activation of skeletal muscle contraction.

Autonomic Nervous System

Parasympathetic Nervous System

Neurotransmitters & Receptors

Preganglionic neuron: releases ACh → binds NN (nicotinic neuronal) receptors.
Postganglionic neuron: releases ACh → binds muscarinic receptors (G-protein coupled).

Key Concepts

Long preganglionic, short postganglionic fibers.
Primary role: “Rest and digest” (e.g., decreased HR, increased GI motility).

Sympathetic Nervous System

Neurotransmitters & Receptors

Preganglionic neuron: releases ACh → binds NN receptor.
Postganglionic neuron (most): releases norepinephrine (NE) → binds α and β receptors (β₁–β₃).

Key Concepts

Short preganglionic, long postganglionic fibers.
Primary role: “Fight or flight” (e.g., ↑ HR, bronchodilation, vasoconstriction).

Peripheral Nervous System Pathways

System	Preganglionic NT → Receptor	Postganglionic NT → Receptor	Notes
Somatic (Motor)	No ganglion	ACh → NM	Fast, well-myelinated
Parasympathetic	ACh → NN	ACh → Muscarinic	Rest & digest
Sympathetic	ACh → NN	NE → α, β (most)	Fight or flight

Review and Integration (Clinical Insights)

This section reinforces physiology with clinically relevant signs and mechanisms.

Key Clinical Connections

Dysfunction in motor neurons or NMJ → weakness, paralysis, fatigability.
Overactivity or blockade of cholinergic systems leads to predictable parasympathetic signs (salivation, bradycardia, miosis).
Excess sympathetic activity → hypertension, tachycardia, sweating.

Bridge to Pharmacology

Botulinum Toxin

A protease that destroys vesicle fusion proteins.
Prevents ACh release from cholinergic neurons → flaccid paralysis.

Black Widow Spider (Latrotoxin)

Opens presynaptic Ca²⁺ channels → excessive ACh release.
Results in painful muscle spasms, abdominal rigidity.

AChE Inhibitors (Pesticides, Some Drugs)

Block acetylcholinesterase → prolonged ACh action.
Leads to cholinergic toxicity: SLUDGE (salivation, lacrimation, urination, defecation, GI upset, emesis).

Neuromuscular Blockers

Non-depolarizing blockers: competitively block NM receptors.
Succinylcholine: depolarizing blocker; keeps channel open → transient fasciculations then paralysis.