An experiment from a dream
In 1914 the British physiologist Henry Dale reported that choline esters mimicked nerve stimulation, slowing the heart and contracting muscle. Around Easter 1921 the Austrian pharmacologist Otto Loewi woke from a dream and ran the experiment it suggested: he stimulated the vagus nerve of a frog heart, then moved the fluid bathing it to a second heart, which slowed too. It was the first proof that nerves signal chemically, through a "Vagusstoff", rather than purely electrically. The substance proved to be acetylcholine, and in 1936 Dale, Wilhelm Feldberg and Marthe Vogt showed it is released at motor nerve endings as well; Dale and Loewi shared that year's Nobel Prize in Physiology or Medicine. In 1954 Bernard Katz showed that acetylcholine is released in fixed "quanta" from vesicles, founding the basic model of signalling between neurons.
What it does in the body and brain
Released from motor nerve endings, acetylcholine opens nicotinic receptors on muscle fibres and makes them contract; in the parasympathetic system it acts through muscarinic receptors to slow the heart and boost saliva and digestive secretions. The enzyme acetylcholinesterase destroys it within about a millisecond, ending the signal. In the brain, cholinergic neurons of the basal forebrain project to the cortex and hippocampus and support attention, learning, working memory and REM sleep; Michael Hasselmo describes acetylcholine as switching the brain into an "encoding" mode for new information. Nicotine's brief boost to concentration comes from stimulating these receptors. With dopamine and serotonin, it is one of the major neuromodulators.
| Receptor | Mechanism | Main sites | Related drugs |
|---|---|---|---|
| Nicotinic | Ion channel | Neuromuscular junction, autonomic ganglia, brain | Nicotine, neuromuscular blockers |
| Muscarinic | G-protein-coupled | Heart, glands, gut, brain | Atropine, scopolamine |
Disease, drugs and poisons
In 1976 Peter Davies and A. J. F. Maloney found that the enzyme that makes acetylcholine is sharply reduced in the brains of people with Alzheimer's disease, and in 1982 Raymond Bartus and colleagues framed the "cholinergic hypothesis". Acetylcholinesterase inhibitors such as donepezil therefore ease dementia symptoms, though they do not halt the disease. In 1973 Jim Patrick and Jon Lindstrom showed that myasthenia gravis is an autoimmune attack on acetylcholine receptors. Conversely, nerve agents such as sarin and some organophosphate pesticides block the breakdown enzyme, flooding synapses and paralysing breathing; atropine is an antidote. Botulinum toxin blocks acetylcholine release and paralyses muscle — the basis of Botox in tiny doses. Seek medical help immediately if poisoning is suspected.
This article is general health information and is not a substitute for diagnosis or treatment. If symptoms persist, see a doctor.
FAQ
- Does eating foods rich in acetylcholine improve memory?
- Acetylcholine itself barely reaches the brain when eaten. Its precursor choline is found in eggs, soy and fish, but evidence that supplements improve memory in healthy people is weak.
- Why are anticholinergic drugs a concern for older adults?
- Some sleep aids, cold remedies and bladder drugs block acetylcholine and can cause confusion, constipation and memory problems in older people. Review combined medicines with a doctor or pharmacist.
Sources reviewed: 2026-10-26
References
- Dale, H. H. (1914). The action of certain esters and ethers of choline, and their relation to muscarine. Journal of Pharmacology and Experimental Therapeutics, 6, 147–190.
- Loewi, O. (1921). Über humorale Übertragbarkeit der Herznervenwirkung. Pflügers Archiv, 189, 239–242.
- Dale, H. H., Feldberg, W., & Vogt, M. (1936). Release of acetylcholine at voluntary motor nerve endings. Journal of Physiology, 86(4), 353–380.
- del Castillo, J., & Katz, B. (1954). Quantal components of the end-plate potential. Journal of Physiology, 124(3), 560–573.
- Patrick, J., & Lindstrom, J. (1973). Autoimmune response to acetylcholine receptor. Science, 180(4088), 871–872.
- Davies, P., & Maloney, A. J. F. (1976). Selective loss of central cholinergic neurons in Alzheimer's disease. The Lancet, 308(8000), 1403.
- Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982). The cholinergic hypothesis of geriatric memory dysfunction. Science, 217(4558), 408–414.
- Unwin, N. (2005). Refined structure of the nicotinic acetylcholine receptor at 4 Å resolution. Journal of Molecular Biology, 346(4), 967–989.
- Hasselmo, M. E. (2006). The role of acetylcholine in learning and memory. Current Opinion in Neurobiology, 16(6), 710–715.