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13.3 Neurotransmitter Systems, CNS/PNS Organisation & Reflex Arcs

Key Takeaways

Acetylcholine is the transmitter at every autonomic preganglionic synapse, at all parasympathetic postganglionic targets, and at the skeletal neuromuscular junction, which is why acetylcholinesterase inhibitors such as organophosphates produce simultaneous muscarinic overstimulation and depolarising neuromuscular blockade.
The sympathetic division uses short preganglionic and long postganglionic fibres releasing noradrenaline for a diffuse fight-or-flight response, whereas the parasympathetic division uses long preganglionic and short postganglionic fibres releasing acetylcholine for discrete rest-and-digest control, with the adrenal medulla acting as a modified sympathetic ganglion that secretes adrenaline directly into the blood.
A monosynaptic reflex arc such as the patellar stretch reflex routes a single sensory neuron directly onto a motor neuron in the spinal cord, producing the shortest possible latency, whereas polysynaptic arcs such as the withdrawal reflex interpose interneurons that permit reciprocal inhibition of antagonist muscles.

Last updated: September 2026

13.3 Neurotransmitter Systems, CNS/PNS Organisation & Reflex Arcs

Neurotransmitter Systems on the MCAT

Neurotransmitter	Primary Synthesis Precursor	Functional Classification	Receptor Types	Key Physiological Roles & Clinical Pathology
Acetylcholine (ACh)	Choline + Acetyl-CoA	Excitatory in skeletal muscle; inhibitory in cardiac pacemaker	Nicotinic (ionotropic; $Na^+/K^+$ channel); Muscarinic (metabotropic $M_1-M_5$ )	Neuromuscular junction; autonomic preganglionic transmission; parasympathetic postganglionic signaling; cognitive memory in hippocampus (depleted in Alzheimer's disease)
Glutamate	Glutamine / $\alpha$ -Ketoglutarate	Primary excitatory transmitter in the CNS	AMPA, Kainate, NMDA (ionotropic $Ca^{2+}/Na^+$ ); mGluR (metabotropic)	Synaptic plasticity, Long-Term Potentiation (LTP); excessive release induces excitotoxic neuronal death during ischemic stroke
GABA ( $\gamma$ -Aminobutyric Acid)	Glutamate (via glutamate decarboxylase + vitamin $B_6$ )	Primary inhibitory transmitter in the brain	$GABA_A$ (ionotropic $Cl^-$ channel); $GABA_B$ (metabotropic $G_i$ , opens $K^+$ channels)	Prevents runaway excitation; target of benzodiazepines, barbiturates, and ethanol (allosteric positive modulators of $GABA_A$ )
Glycine	Serine	Primary inhibitory transmitter in spinal cord & brainstem	Glycine receptor (ionotropic $Cl^-$ channel)	Mediates recurrent inhibition of motor neurons (Renshaw cells); blocked by strychnine toxin, producing fatal spastic tetany
Dopamine	L-Tyrosine $\to$ L-DOPA	Modulatory biogenic amine (catecholamine)	$D_1$ -like ( $G_s$ , $\uparrow$ cAMP); $D_2$ -like ( $G_i$ , $\downarrow$ cAMP)	Voluntary motor control (substantia nigra pars compacta; degenerates in Parkinson's disease); reward/addiction pathway (mesolimbic); schizophrenia (dopamine hypothesis)
Norepinephrine (NE)	Dopamine (via dopamine $\beta$ -hydroxylase)	Excitatory/modulatory catecholamine	$\alpha_1$ ( $G_q$ ), $\alpha_2$ ( $G_i$ ), $\beta_1$ ( $G_s$ ), $\beta_2$ ( $G_s$ ), $\beta_3$ ( $G_s$ )	Sympathetic postganglionic transmitter; wakefulness, alertness, fight-or-flight response; synthesized in locus coeruleus of brainstem
Serotonin (5-HT)	L-Tryptophan	Modulatory monoamine (indolamine)	$5\text{-HT}_3$ (ionotropic cation channel); $5\text{-HT}_{1,2,4-7}$ (metabotropic)	Regulation of mood, sleep-wake cycle, appetite, gut peristalsis (90% synthesized in enterochromaffin cells of GI tract); synthesized in raphe nuclei

Structural Organization: CNS vs. PNS & Somatic vs. Autonomic

The human nervous system is divided anatomically into:

Central Nervous System (CNS): Brain and spinal cord, encased by bone (cranium, vertebral column) and three layers of meninges (dura mater, arachnoid mater, pia mater).
Peripheral Nervous System (PNS): 12 pairs of cranial nerves and 31 pairs of spinal nerves connecting the CNS to peripheral tissues.

Functionally, the motor (efferent) division of the PNS is partitioned into:

Somatic Nervous System: Controls voluntary movements of skeletal muscles. It utilizes a single lower motor neuron whose cell body resides in the ventral horn of the spinal cord (or cranial motor nuclei) and projects its myelinated axon directly to the target skeletal muscle fiber without intervening peripheral synapses. It releases acetylcholine (ACh) onto nicotinic acetylcholine receptors ( $N_M$ ), invariably producing excitation.
Autonomic Nervous System (ANS): Controls involuntary visceral functions (smooth muscle, cardiac muscle, exocrine glands). It operates through a two-neuron relay chain:
- Preganglionic Neuron: Soma resides in the CNS; projects a lightly myelinated axon to an autonomic ganglion.
- Postganglionic Neuron: Soma resides within the peripheral autonomic ganglion; sends an unmyelinated axon to the effector organ.

Sympathetic vs. Parasympathetic Divisions

Sympathetic Nervous System (Thoracolumbar Outflow):
- Prepares the organism for energy expenditure and emergencies ("Fight-or-Flight").
- Outflow originates from the lateral horns of spinal cord segments $T1-L2$ .
- Anatomy: Short preganglionic fibers release ACh onto nicotinic receptors ( $N_N$ ) in the sympathetic chain ganglia (paravertebral) or prevertebral ganglia (celiac, mesenteric). Long postganglionic fibers project to targets and release norepinephrine (NE) onto adrenergic receptors ( $\alpha_1, \alpha_2, \beta_1, \beta_2$ ).
- Exceptional Sympathetic Targets: Sweat glands are innervated by sympathetic postganglionic neurons that release acetylcholine onto muscarinic receptors. The adrenal medulla is innervated directly by preganglionic sympathetic fibers that release ACh onto chromaffin cells (modified postganglionic neuroendocrine cells), which secrete epinephrine (80%) and norepinephrine (20%) directly into the bloodstream.
Parasympathetic Nervous System (Craniosacral Outflow):
- Promotes energy conservation, digestion, and basal maintenance ("Rest-and-Digest").
- Outflow originates from cranial nerve nuclei (CN III [Oculomotor], CN VII [Facial], CN IX [Glossopharyngeal], CN X [Vagus]) and sacral spinal cord segments $S2-S4$ .
- The vagus nerve (CN X) provides extensive parasympathetic innervation to the thoracic and abdominal viscera (heart, lungs, stomach, intestines).
- Anatomy: Long preganglionic fibers travel to terminal or intramural ganglia located on or directly within target organs, releasing ACh onto nicotinic receptors ( $N_N$ ). Short postganglionic fibers release ACh onto muscarinic receptors ( $M_1-M_5$ ) on target tissues.

Spinal Reflex Arcs: Monosynaptic vs. Polysynaptic

A reflex arc is an involuntary, stereotyped neural circuit that mediates a rapid motor response to a specific sensory stimulus without requiring conscious cortical intervention:

Monosynaptic Reflex Arc: Consists of only one chemical synapse between the primary afferent sensory neuron and the efferent motor neuron.
- Example: Patellar Tendon (Knee-Jerk) Stretch Reflex: Tapping the patellar tendon stretches the quadriceps femoris muscle and activates muscle spindle stretch receptors. Type Ia sensory afferent fibers enter the dorsal horn of the spinal cord and directly synapse onto $\alpha$ -motor neurons in the ventral horn. These motor neurons fire, sending action potentials along their axons to elicit contraction of the quadriceps, extending the lower leg.
Polysynaptic Reflex Arc: Contains at least one interneuron interposed between the sensory afferent and motor efferent pathways.
- Reciprocal Inhibition: In the patellar reflex, the same sensory afferent also synapses onto an inhibitory interneuron in the spinal cord that suppresses the $\alpha$ -motor neurons of the antagonistic hamstring muscles, preventing counteracting contraction.
- Flexor Withdrawal and Crossed-Extensor Reflex: Stepping on a sharp nail triggers nociceptors (pain fibers) that enter the spinal cord. Polysynaptic circuits excite ipsilateral flexor motor neurons (withdrawing the injured foot) while inhibiting ipsilateral extensors. Concurrently, collateral interneurons cross the midline to excite contralateral extensor motor neurons and inhibit contralateral flexors, stiffening the opposite leg to maintain upright posture and balance.

Test Your Knowledge

A patient experiences sudden visual and autonomic disturbances following accidental exposure to an organophosphate pesticide. The chemical works as a potent, irreversible inhibitor of acetylcholinesterase. Which set of autonomic and somatic findings would most consistently present in this patient?

Mydriasis (pupillary dilation), severe tachycardia, urinary retention, and enhanced skeletal muscle relaxation.

Bronchodilation, reduced gastrointestinal peristalsis, extreme xerostomia (dry mouth), and hyporeflexia.

Miosis (pupillary constriction), severe bradycardia, profuse salivation and diarrhea, and skeletal muscle fasciculations transitioning to flaccid paralysis.

Elevated systemic vascular resistance, pupillary dilation, dry skin, and selective blockade of central sympathetic outflow.

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