The Synapse and Neurotransmission

Structure of a chemical synapse. Most synapses are chemical: the two cells don't touch but are separated by a microscopic gap, the synaptic cleft. The presynaptic neuron's axon terminal contains vesicles filled with neurotransmitter. The postsynaptic cell has receptors for that neurotransmitter on its membrane. The signal must cross the gap chemically because the electrical action potential itself cannot jump the cleft.

The sequence of neurotransmission. Passing a signal across a chemical synapse follows a reliable sequence:

1. The action potential arrives at the axon terminal.
2. It triggers calcium to enter the terminal.
3. Calcium causes synaptic vesicles to release neurotransmitter into the cleft (by exocytosis).
4. Neurotransmitter diffuses across the cleft and binds receptors on the postsynaptic cell.
5. This binding changes the postsynaptic membrane (opening ion channels), making the cell more or less likely to fire.
6. The neurotransmitter is quickly removed — broken down by enzymes, taken back up (reuptake), or diffused away — so the signal is brief and controlled.

Notice calcium appears again as the trigger for release, echoing muscle contraction — a recurring theme.

Excitatory vs inhibitory. A neurotransmitter's effect depends on the receptor it binds:

• Excitatory signals depolarize the postsynaptic cell (make the inside less negative), pushing it toward threshold and firing.
• Inhibitory signals hyperpolarize it (make it more negative), pushing it away from threshold, making firing less likely.

Each neuron constantly sums thousands of excitatory and inhibitory inputs; it fires only if the net effect reaches threshold. This integration is how the nervous system makes decisions rather than passing every signal blindly.

Major neurotransmitters. Different neurotransmitters dominate different functions (and are targets of many drugs):

• Acetylcholine (ACh): neuromuscular junctions (muscle contraction) and many autonomic synapses; also involved in memory (reduced in Alzheimer's disease).
• Dopamine: movement, reward, and motivation (deficiency in Parkinson's disease; dysregulation implicated in addiction and psychosis).
• Serotonin: mood, sleep, appetite (a target of many antidepressants).
• Norepinephrine: alertness and the "fight or flight" response.
• GABA: the main inhibitory neurotransmitter in the brain (calming; targeted by anti-anxiety drugs).
• Glutamate: the main excitatory neurotransmitter in the brain (learning and memory).
• Endorphins: natural pain relievers.

How it works

Crossing the synapse:

Action potential reaches terminal → calcium enters
   → neurotransmitter released into the cleft
   → binds receptors on the postsynaptic cell
   → excitatory (toward threshold) or inhibitory (away)
   → cell sums all inputs; fires if it reaches threshold
   → neurotransmitter cleared (enzyme, reuptake, diffusion)

Comparisons

Common confusions

• Excitatory ≠ "good," inhibitory ≠ "bad." Both are essential; balance matters (too much excitation can cause seizures).
• Neurotransmitter effect depends on the receptor, not just the chemical — the same transmitter can excite one cell and inhibit another.
• Reuptake vs breakdown. Both end the signal; many drugs work by blocking reuptake (prolonging the signal).
• Calcium triggers release at the terminal — a recurring role for calcium.

Memory aids

• "Excite = toward firing (depolarize); Inhibit = away (hyperpolarize)."
• GABA = "the brakes; Glutamate = the gas."
• Dopamine + movement = "Parkinson's runs low on dopamine."

Quick review

• At a chemical synapse, an action potential triggers calcium entry, which releases neurotransmitter across the synaptic cleft to bind receptors on the postsynaptic cell.
• Effects are excitatory (depolarize, toward firing) or inhibitory (hyperpolarize, away); neurons sum all inputs to decide whether to fire.
• Major neurotransmitters: ACh, dopamine, serotonin, norepinephrine, GABA (inhibitory), glutamate (excitatory), endorphins.
• Synapses are the main site of drug action — a foundation for pharmacology.