Psychology › Brain & biology › Neurons and synapses
Neurotransmitters, the brain's chemical messengers
First found 1921· Concept
Well replicatedStrong, repeated evidence.
Chemicals that neurons release at synapses to excite or quiet the next cell; more than 100 are known.
See it on the Psychology map →What it says
In 1921 Otto Loewi, by his account inspired by a dream, bathed two frog hearts in fluid. Stimulating the first heart's nerve slowed it; moving its fluid onto the second heart slowed that one too. The nerve had released a chemical, later identified as acetylcholine. Most brain signaling uses glutamate (excite) and GABA (calm). Smaller systems, such as dopamine, serotonin and norepinephrine, tune mood, attention and motivation. Caffeine, alcohol and nicotine work by altering these chemical systems.
Why it matters
It made the brain chemically treatable. Antidepressants, antipsychotics, anesthetics and anti-anxiety drugs all act on neurotransmitter systems, as do most recreational drugs.
The evidence
Status: well replicated. Loewi and Henry Dale shared the 1936 Nobel Prize. Today transmitters are measured directly, blocked with drugs and tracked in living brains with PET scans.
Open questions
How chemistry maps onto experience: no single chemical equals one mood, and why the same drug helps one person but not another is largely unknown.
Inside this (2)
Connections (4)
▸Neurotransmitters, the brain's chemical messengers carry signals between Neurons and synapsesWell replicated
The connection
Inside a neuron the signal is electrical; between neurons it becomes chemical. When an impulse reaches the axon's tip, tiny packets spill neurotransmitter into the synapse. The molecules cross the gap in under a millisecond, lock onto receptors on the next cell, and push it toward firing or quiet it. Pumps then recycle them, which is where many drugs act.
Who showed it and when
Otto Loewi's frog-heart experiment, Graz, Austria, 1921; Bernard Katz's studies of transmitter 'packets' in London in the 1950s; Julius Axelrod's work on recycling (reuptake) in the US.
The evidence
Nobel Prizes in 1936 (Loewi, Dale) and 1970 (Katz, Axelrod, von Euler); electron microscopes later showed the packets and synaptic gaps directly.
Open questions
Some neurons also connect through direct electrical synapses, and one neuron can release several chemicals at once; how these mixtures carry information is still being mapped.
▸Dopamine, reward and prediction error is one of the Neurotransmitters, the brain's chemical messengersWell replicated
The connection
Dopamine is one of the brain's 'modulating' neurotransmitters. Fewer than a million human neurons make it, clustered in the midbrain, yet their fibers reach wide areas and adjust how other circuits respond. It belongs to the same chemical family, the monoamines, as serotonin and norepinephrine, which is why many drugs affect several of them at once.
Who showed it and when
Arvid Carlsson's lab in Lund, Sweden, 1957–58, showed dopamine is a transmitter in its own right, not just a building block for norepinephrine as had been assumed.
The evidence
Carlsson reversed drug-induced Parkinson-like stiffness in rabbits with L-DOPA, which the brain turns into dopamine; it still treats Parkinson's, and he shared the 2000 Nobel Prize.
Open questions
Dopamine neurons can also release glutamate or GABA, blurring the neat 'one neuron, one chemical' picture; what this co-release does is still being studied.
▸Serotonin is one of the Neurotransmitters, the brain's chemical messengersWell replicated
The connection
Serotonin is another monoamine neurotransmitter. A few hundred thousand brainstem neurons make it for the brain, but their branches reach nearly every region. At least 14 receptor types respond to it in different ways, which is why drugs as different as Prozac, LSD and anti-nausea pills all work through serotonin.
Who showed it and when
Isolated at the Cleveland Clinic in 1948; found in mammal brains by Betty Twarog and Irvine Page in 1953, which suggested it acted as a brain messenger.
The evidence
Brain tissue studies, receptor mapping and drug effects. In the 1950s, LSD's chemical resemblance to serotonin helped convince scientists that serotonin acts in the brain.
Open questions
What serotonin's core job is: theories include patience, coping with stress and adapting to setbacks, but no single function has won consensus.
▸Ketamine and esketamine for depression target glutamate among Neurotransmitters, the brain's chemical messengersWell replicated
The connection
Most antidepressants act on serotonin or norepinephrine. Ketamine instead blocks NMDA receptors, a main receiver for glutamate, the brain's chief excitatory messenger. This seems to trigger a brief glutamate surge and rapid growth of synaptic connections in mood circuits, which may explain its speed.
Who showed it and when
Ronald Duman and George Aghajanian's labs at Yale showed in 2010 that ketamine regrows synapses in rats within a day.
The evidence
In rats, blocking the downstream signaling protein mTOR blocks both synapse growth and the antidepressant effect. Human evidence is indirect, from brain imaging and blood markers.
Open questions
A 2018 Stanford study found an opioid blocker dampened ketamine's effect, hinting at opioid involvement; other teams disputed this. The mechanism remains debated.