Neurons communicate with each other mainly via
chemical messages, or neurotransmitters. When a neuron is sufficiently stimulated, an electrical
impulse called an action potential is generated and travels down the axon to the nerve
terminal. Here, it triggers the release of a neurotransmitter into the synaptic cleft
- a space between neurons. The neurotransmitter then binds to a receptor on a neighboring
neuron, generating a signal in it, thereby transmitting the information to that neuron.
The neuron that releases the neurotransmitter is the pre-synaptic neuron, while the one that
receives the signal is the post-synaptic neuron. The axon of the pre-synaptic neuron may
form a synapse with either a dendrite, the cell body, or the axon of the post-synaptic
neuron, giving rise to an axodendritic, axosomatic, or axoaxonic synapse, respectively.
Chemical synapses exist not only between neurons, but also between a neuron and a target
cell, such as muscle, or gland cell. Over a hundred of neurotransmitters
have been identified so far. Most of them can be grouped into classes
according to their chemical structure. Major classes include:
- Amino acids, such as glycine, glutamate, aspartate, and GABA.
- Small peptides, called neuropeptides, such as beta-endorphin and substance P.
- Monoamines, such as epinephrine, norepinephrine, dopamine, serotonin, and histamine. Monoamines are
basically amino acids with the acid group removed. - And acetylcholine, an ester of
choline, in its own class by itself. Neurotransmitters are synthesized in the
presynaptic neuron and stored in small sacs, called synaptic vesicles, at the axon terminal.
Some of these vesicles are docked on plasma membrane, ready to release neurotransmitter on
demand. When an action potential arrives at the nerve terminal, the resulting depolarization
opens voltage-gated calcium channels, allowing calcium to flow in. Calcium causes
the vesicles to fuse with plasma membrane, releasing the neurotransmitter
in a process known as exocytosis. Upon binding to their receptors on the
postsynaptic cell, some neurotransmitters open ligand-gated ion channels, causing direct changes
to membrane potential of the receiving neuron, while others act through second-messenger
systems to exert their effect. Some neurotransmitters are excitatory,
others are inhibitory; and for some, the effect can be either excitatory or inhibitory
depending on the receptor they bind to. An example of excitatory neurotransmitter is
glutamate. Upon binding, it triggers glutamate receptors, ligand-gated ion channels, to open
and allow positively-charged ions into the cell, making it more positive, less polarized, and
thus more likely to generate action potentials. On the other hand, GABA, a major
inhibitory neurotransmitter, opens ligand-gated chloride channels to
allow negatively-charged chloride to enter, making the cell more negative, more polarized, and
thus less likely to generate action potentials. Acetylcholine is a neurotransmitter that can
be either excitatory or inhibitory depending on the receptor present on the target cell.
At neuromuscular junctions, acetylcholine released by motor neurons binds to nicotinic
receptors on skeletal muscle cells and stimulates them to contract. On the other hand, it inhibits
cardiac muscle cells via muscarinic receptor M2, causing heart rate to slow down, as part of
the parasympathetic “rest and digest” response. A neurotransmitter binds to its
receptor for only a millisecond or so. It then passively diffuses from the synapse and
is taken up by nearby astrocytes for recycling. If the presynaptic neuron continues to
fire and release more neurotransmitter, new molecules will bind and again
activate the receiving neuron. If the presynaptic signal stops coming,
the transmission will eventually stop. There also exist mechanisms to actively remove
neurotransmitters from the synaptic space to avoid overstimulation. Common mechanisms include:
- degradation of the neurotransmitter by an enzyme present in the synapse;
- and reuptake, where the neurotransmitter is transported back, by a transporter
protein, to the presynaptic neuron for reuse.