Neurons communicate with one another through a combination of electrical signals and chemical messengers. Inside a neuron, information is often carried as an electrical signal. Between neurons, however, the message usually crosses a tiny gap using chemicals called neurotransmitters.
This process happens at specialized junctions called synapses. A neuron releases neurotransmitter molecules from one end, those molecules cross the synaptic gap, and they bind to receptors on the next cell. The receptors then change the activity of the receiving neuron, either making it more likely to send its own signal or less likely to do so.
The basic sequence is simple, but the underlying mechanism is tightly coordinated. It depends on electrical changes in the neuron, calcium ions, membrane-bound storage compartments called vesicles, receptors, and several ways of clearing the chemical signal.
Where neuron-to-neuron communication happens
Most neuron-to-neuron communication occurs at a chemical synapse. The neuron sending the message is called the presynaptic neuron, while the cell receiving it is the postsynaptic neuron.
At a typical chemical synapse, the presynaptic neuron’s axon ends in a small structure called an axon terminal. The terminal is separated from the receiving cell by a microscopic space called the synaptic cleft.
Neurotransmitters are stored inside small membrane-bound sacs, or synaptic vesicles, in the axon terminal. When the neuron is activated, these vesicles can release their contents into the synaptic cleft.
The neurotransmitters then bind to specialized proteins called receptors on the postsynaptic cell. A receptor recognizes particular chemical signals and converts the binding event into a change in the receiving cell.
That is how a message moves from one neuron to another without the two cells physically touching.
The electrical signal triggers chemical release
A neuron does not continuously release neurotransmitters. Release is triggered when an electrical signal called an action potential reaches the axon terminal.
An action potential is a rapid change in the electrical voltage across the neuron’s membrane. It travels along the axon and reaches the terminal, where it causes voltage-sensitive calcium channels to open.
Calcium ions are normally present at a much higher concentration outside the neuron than inside it. When these channels open, calcium rapidly enters the axon terminal.
That calcium influx is the critical trigger for neurotransmitter release. It causes certain synaptic vesicles to move into position and fuse with the neuron’s cell membrane. The vesicle then empties its neurotransmitters into the synaptic cleft through a process called exocytosis.
The sequence can be summarized as:
Action potential → calcium entry → vesicle fusion → neurotransmitter release
This connection between an electrical event and chemical release is one of the defining features of chemical synaptic communication.
Neurotransmitters cross the synaptic cleft
Once released, neurotransmitter molecules diffuse across the synaptic cleft. The distance is extremely small, so this part of the process occurs rapidly.
The neurotransmitter does not simply enter the next neuron and carry the electrical signal onward. Instead, it binds to receptors embedded in the receiving cell’s membrane.
Different neurotransmitters interact with different receptor types, and the same neurotransmitter can sometimes produce different effects depending on which receptor it activates.
This is an important point: a neurotransmitter’s effect is determined largely by the receptor it activates, not simply by the chemical’s name.
For example, the neurotransmitter acetylcholine can produce excitation in some cells and different effects in others because different cells can carry different acetylcholine receptors.
Receptors turn the chemical message back into a cellular signal
There are two major types of neurotransmitter receptors: ionotropic receptors and metabotropic receptors.
Ionotropic receptors act quickly
Ionotropic receptors are essentially neurotransmitter-controlled ion channels. When a neurotransmitter binds to one, the channel opens and allows particular ions to cross the cell membrane.
The movement of these ions changes the electrical state of the postsynaptic cell.
For instance, some receptor channels allow positively charged ions to enter, making the inside of the neuron less negative. This can produce an excitatory postsynaptic potential, or EPSP, which makes the neuron more likely to generate an action potential.
Other receptors increase the movement of ions in a way that makes the neuron less likely to fire, producing an inhibitory postsynaptic potential, or IPSP.
Ionotropic signaling is typically fast because receptor activation directly controls an ion channel.
Metabotropic receptors act through cellular signaling pathways
Metabotropic receptors work differently. Rather than forming an ion channel themselves, they activate intracellular signaling mechanisms, commonly involving G proteins and other signaling molecules.
These pathways can alter ion channels, enzymes, metabolism, and other cellular processes. Their effects are generally slower to develop and can last longer than those produced by ionotropic receptors.
This gives neurons a way to adjust their activity more broadly than simply switching an ion channel on or off.
A neurotransmitter can excite or inhibit depending on the receptor
It is tempting to classify neurotransmitters as either “excitatory” or “inhibitory,” but that description is an oversimplification.
Whether a neurotransmitter excites or inhibits a neuron depends on factors such as the receptor involved, the ions that receptor controls, and the state of the receiving cell.
Glutamate, for example, is the major excitatory neurotransmitter in the brain under typical conditions, while GABA is the major inhibitory neurotransmitter in the mature central nervous system. But their effects still depend on receptor properties and cellular context.
The distinction matters because neurons receive thousands of signals from other cells. Some increase the likelihood that the neuron will fire; others decrease it.
Neurons combine many incoming messages
A neuron usually does not respond to just one synaptic input. Its dendrites and cell body can receive signals from many other neurons simultaneously.
The neuron integrates these inputs. Excitatory and inhibitory changes in its membrane voltage can add together over space and time. If the combined effect at the neuron’s axon initial segment reaches the threshold needed to trigger an action potential, the neuron fires.
This is why synaptic communication is better understood as information processing than as a simple chain of one chemical message followed by another.
A neuron might receive excitatory input from several sources while also receiving inhibitory input from others. The final electrical response reflects the combined influence of these signals.
The message must be stopped
Neurotransmitters cannot remain active indefinitely. Once they have transmitted their signal, they must be removed or their effects must otherwise be terminated.
Several mechanisms accomplish this.
Reuptake occurs when transporter proteins move neurotransmitters back into the presynaptic neuron or into nearby support cells. The molecules can then be recycled, broken down, or otherwise processed.
Enzymatic breakdown uses enzymes to chemically modify or destroy neurotransmitter molecules. Acetylcholine, for example, is rapidly broken down in the synaptic cleft by the enzyme acetylcholinesterase.
Diffusion also moves neurotransmitter molecules away from the synaptic cleft, where they may eventually be taken up or broken down.
The precise combination of mechanisms varies among neurotransmitters and synapses. Efficient signal termination is essential because neurons need to distinguish one signal from the next.
What happens after a neurotransmitter is released?
The complete process can be viewed as a chain of linked events:
- An action potential travels down the presynaptic neuron’s axon.
- The action potential reaches the axon terminal.
- Voltage-sensitive calcium channels open.
- Calcium enters the terminal.
- Calcium triggers synaptic vesicles to fuse with the membrane.
- Neurotransmitter molecules enter the synaptic cleft.
- The molecules bind to receptors on the postsynaptic cell.
- Receptor activation changes the receiving cell’s electrical or biochemical state.
- The neurotransmitter is removed, broken down, or taken back up.
- The postsynaptic neuron integrates the resulting signal with other inputs.
If the resulting changes are sufficient to reach threshold at the appropriate part of the neuron, the postsynaptic neuron generates its own action potential and can pass the message onward.
Not all neural communication uses neurotransmitters
Chemical synapses are extremely important, but neurons can also communicate through electrical synapses.
At an electrical synapse, specialized structures called gap junctions directly connect neighboring cells. Ions can pass between the cells, allowing electrical activity to spread directly from one cell to another.
Electrical synapses are generally faster than chemical synapses, but chemical synapses offer much greater flexibility. Chemical signaling can be excitatory or inhibitory, can activate different receptor types, and can engage complex intracellular signaling pathways.
Neurons can therefore use different forms of communication depending on the function the circuit needs to perform.
Neurotransmitters are part of a larger signaling system
Neurotransmitters do more than simply relay information from one neuron to another. Their effects can influence attention, movement, learning, memory, mood, sleep, sensation, and many other functions by changing how neural circuits operate.
Some important neurotransmitters include glutamate, GABA, acetylcholine, dopamine, serotonin, and norepinephrine. They differ in where they are produced, which receptors they activate, how they are removed, and what kinds of neural circuits they influence.
Many drugs and medications affect these signaling systems by changing neurotransmitter release, receptor activity, reuptake, or breakdown. Because a single neurotransmitter can act through multiple receptor types, altering a signaling system can have different effects in different parts of the nervous system.
The essential principle, however, remains consistent: an electrical signal reaches the end of one neuron, triggers the release of chemical messengers, and those messengers alter the activity of another cell by binding to its receptors. This rapid conversion between electrical and chemical signals allows networks of neurons to communicate, integrate information, and generate the coordinated activity underlying the nervous system.
