In 1921 the pharmacologist Otto Loewi, working in Austria, ran an experiment that by his own account came to him in a dream. He stimulated the vagus nerve of a frog's heart, which slowed its beat. Then he took fluid from around that heart and applied it to a second frog heart. The second heart slowed too. A chemical, not just electricity, had carried the message. Loewi called it Vagusstoff ("vagus substance"); it was later identified as acetylcholine, and he shared the 1936 Nobel Prize in Physiology or Medicine with Henry Dale.
The neuron
A neuron is a nerve cell. Dendrites receive messages, the cell body keeps the cell alive, and the axon carries the signal away toward other cells. Many axons are wrapped in a fatty myelin sheath that speeds signals up; damage to myelin is part of multiple sclerosis. Glial cells support neurons by making myelin, supplying nutrients and clearing debris.
The action potential
At rest a neuron is slightly negative inside, roughly -70 millivolts. Incoming signals push it up or down. If the charge reaches threshold, the neuron fires an action potential: ions rush across the membrane and an electrical impulse travels down the axon.
Firing is all-or-none. A neuron fires fully or not at all, so a stronger stimulus doesn't make a bigger impulse. It makes the neuron fire more often, and recruits more neurons. After firing there's a brief refractory period when the neuron can't fire again.
The synapse
At most synapses, neurons don't touch. At the synapse, the axon terminal releases neurotransmitters into a tiny gap. They bind to receptors on the next cell, then are cleared away, either broken down by enzymes or reabsorbed by the sending neuron in reuptake.
Excitatory vs inhibitory
An excitatory signal makes the next neuron more likely to fire; an inhibitory one makes it less likely. Each neuron adds up thousands of inputs, and only fires if the total crosses threshold.
The main neurotransmitters
- Acetylcholine: muscle contraction, attention and memory. Neurons that make it are lost in Alzheimer's disease.
- Dopamine: movement, motivation and learning from rewards. Losing dopamine neurons causes Parkinson's movement symptoms.
- Serotonin: mood, sleep, appetite and digestion.
- Norepinephrine: alertness and the fight-or-flight response.
- GABA: the brain's main inhibitory neurotransmitter.
- Glutamate: the brain's main excitatory neurotransmitter, important for learning.
- Endorphins: the body's own opioids, which reduce pain.
Agonists and antagonists
An agonist mimics or boosts a neurotransmitter. Morphine works by activating the same receptors as endorphins. An antagonist blocks one. Naloxone blocks opioid receptors, and curare blocks acetylcholine receptors on muscles, causing paralysis. SSRIs, a class of antidepressant, block the reuptake of serotonin so it stays in the synapse longer.
Myths, then the fix
- "Dopamine is the pleasure chemical." In the 1990s Wolfram Schultz found that dopamine neurons in monkeys fired most when a reward was better than expected. Kent Berridge's research suggests dopamine drives wanting a reward more than liking it. It's better described as a motivation and learning signal.
- "Serotonin is the happiness chemical." Serotonin plays a role in mood, but it's also involved in sleep, appetite and digestion, and most of the body's serotonin is made in the gut. No single chemical is "happiness".
Where the research is shaky
For decades depression was popularly explained as a "chemical imbalance", usually low serotonin. A 2022 umbrella review led by Joanna Moncrieff found no consistent evidence that depression is caused by low serotonin. Other researchers criticized that review, and serotonin's exact role is still debated. Many researchers describe depression as involving many interacting biological, psychological and social factors. The debate is about cause; whether a treatment helps a particular person is a separate question, and one for a doctor.
Common mix-ups
- All-or-none describes one neuron's impulse, not the whole brain switching on.
- Reuptake recycles a neurotransmitter; it isn't the same as an enzyme breaking it down.
- Agonist vs antagonist. Binding to a receptor isn't enough to make something an agonist. It has to activate it.
Frequently asked questions
What are the main neurotransmitters and their functions?
Acetylcholine (muscles, memory), dopamine (movement, motivation), serotonin (mood, sleep, appetite), norepinephrine (alertness), GABA (main inhibitor), glutamate (main exciter) and endorphins (pain relief).
Is dopamine the pleasure chemical?
Not quite. Research links dopamine more to motivation, wanting and learning which rewards to pursue than to the feeling of pleasure itself.
Does low serotonin cause depression?
The evidence doesn't show that low serotonin alone causes depression, and serotonin's role is still debated. If low mood lasts or gets in the way of daily life, talk to a doctor or mental health professional.
What is the difference between an agonist and an antagonist?
An agonist mimics or boosts a neurotransmitter's effect; an antagonist blocks it.
Try it
Ask a friend to hold a ruler vertically, with its bottom end between your open thumb and finger, and drop it without warning. Catch it and note how far it fell. In that fraction of a second, signals passed from your eyes through chains of neurons and synapses to the muscles of your hand.