Acetylcholine is an organic molecule that functions as a chemical messenger in the nervous system, known scientifically as a neurotransmitter and neuromodulator. It is an ester of acetic acid and choline, synthesized by neurons and released to communicate with other cells. Acetylcholine is active in both the central nervous system (the brain and spinal cord) and the peripheral nervous system, which extends throughout the body.
The discovery of acetylcholine’s functional significance in the early 20th century marked a defining moment in neuroscience. Physiologist Otto Loewi demonstrated that stimulating the vagus nerve released a substance, which he called “vagusstoff,” that slowed the heart rate. This substance was later identified as acetylcholine, making it the first neurotransmitter to be chemically identified.
Acetylcholine and Voluntary Movement
The most direct and widely recognized function of acetylcholine occurs within the somatic nervous system, controlling voluntary muscle movements. Every conscious movement, from lifting a finger to running, relies on a precise signal transmitted by this molecule at the junction where a nerve meets a muscle fiber, known as the Neuromuscular Junction (NMJ).
When a motor neuron sends a signal, an electrical impulse travels down the nerve fiber to the NMJ. This impulse prompts the neuron to release stored acetylcholine into the synaptic cleft, the narrow gap between the nerve ending and the muscle cell. The acetylcholine molecules then diffuse across this space and bind to specific nicotinic acetylcholine receptors on the muscle cell membrane.
The binding of acetylcholine causes a temporary opening of channels within these receptors, allowing positively charged sodium ions to rush into the muscle cell. This influx of positive charge changes the electrical potential of the muscle cell membrane, a process called depolarization. If depolarization reaches a sufficient threshold, it generates an action potential that spreads deep into the muscle fiber, triggering the release of internal calcium stores. The resulting rise in calcium concentration inside the muscle cell causes the muscle proteins to slide past each other, leading to muscle contraction.
Regulating Internal Organ Function
Beyond the voluntary control of skeletal muscles, acetylcholine plays a foundational role in the autonomic nervous system, which automatically regulates the body’s internal environment. This system controls involuntary actions such as breathing, heart rate, and digestion. Acetylcholine is the primary neurotransmitter for the parasympathetic branch, often termed the “rest and digest” system.
In the cardiovascular system, acetylcholine acts to slow the heart rate and decrease the force of cardiac muscle contraction. It also promotes the dilation of blood vessels, which helps lower blood pressure. This action counterbalances the effects of the sympathetic “fight or flight” system, facilitating a return to a resting state.
Acetylcholine also stimulates activity in the gastrointestinal and urinary tracts. It increases peristalsis, the rhythmic contractions of smooth muscle that move food through the digestive system. It also stimulates the secretion of digestive juices, saliva, and tears by activating various glands. This coordinated action ensures the body conserves energy and replenishes resources during periods of rest.
Impact on Learning and Cognition
In the central nervous system, acetylcholine acts as a neuromodulator that influences higher-order cognitive functions. Cholinergic neurons project widely throughout the cerebral cortex and hippocampus, areas linked to complex thought and memory processing. These projections mostly originate from the basal forebrain, particularly the nucleus basalis of Meynert.
Acetylcholine signaling is involved in processes requiring sustained mental effort, such as attention and concentration. It improves the signal-to-noise ratio in sensory processing, helping the brain filter out irrelevant information to focus on what is important. This modulation is accomplished by binding to muscarinic and nicotinic receptors located on different types of neurons throughout the cortex.
The molecule is also connected to the formation and consolidation of memories. Elevated levels of acetylcholine, detected in the hippocampus during memory tasks, suggest it facilitates the necessary changes in neuronal connections for long-term memory storage. The cholinergic system also helps regulate the sleep-wake cycle, contributing to arousal and wakefulness, with neurons firing maximally during periods of alertness and rapid eye movement (REM) sleep.
When Acetylcholine Signaling Goes Awry
The precise function of acetylcholine is maintained by the enzyme acetylcholinesterase, which rapidly breaks down the molecule in the synapse to terminate the signal. When this system is disrupted, the consequences can be seen in debilitating conditions affecting both muscle control and cognition. Two primary examples illustrate the impact of cholinergic dysfunction in the peripheral and central nervous systems.
Myasthenia Gravis is an autoimmune disorder where the body produces antibodies that attack the nicotinic acetylcholine receptors at the neuromuscular junction. These antibodies block or destroy the receptors, preventing acetylcholine from binding effectively and initiating muscle contraction. This results in progressive, fluctuating muscle weakness, often affecting the eyes, face, and throat, causing drooping eyelids and difficulty swallowing.
In the central nervous system, the deterioration of cholinergic signaling is a feature of Alzheimer’s disease. The condition is associated with a loss of acetylcholine-producing neurons in the basal forebrain, leading to a deficiency of the neurotransmitter in the brain’s memory and learning centers. To combat this decline, treatments often involve Acetylcholinesterase Inhibitors (AChEIs). These drugs work by temporarily blocking the acetylcholinesterase enzyme, allowing the limited acetylcholine released to remain in the synapse longer, boosting the signal and providing symptomatic relief for cognitive decline.