01 / 20

Synaptic Transmission
& Neurotransmitters

Explore how neurons communicate across the synaptic cleft using chemical messengers, and discover the mechanisms that underlie every thought, movement, and sensation.

Anatomy & Physiology

What Is a Synapse?

A synapse is the specialized junction where one neuron communicates with another neuron, a muscle cell, or a gland cell. It is the fundamental unit of neural communication. The tiny gap between the two cells is called the synaptic cleft, typically about 20 to 40 nanometers wide.

Key Structures of the Synapse

Presynaptic Terminal
The axon terminal of the sending neuron. Contains synaptic vesicles filled with neurotransmitter molecules.
Synaptic Cleft
The narrow extracellular gap between the two neurons. Neurotransmitters diffuse across this space.
Postsynaptic Membrane
The membrane of the receiving cell. Contains receptor proteins that bind neurotransmitters.

Anatomy of a Chemical Synapse

Presynaptic Terminal Vesicle Mitochondrion
\(\text{Ca}^{2+}\) Channel
 Synaptic Cleft Neurotransmitters Postsynaptic Cell Receptors Ion Channel Signal Direction

Steps of Synaptic Transmission

1
Action potential arrives at the presynaptic terminal, depolarizing the membrane.
2
Voltage-gated \(\text{Ca}^{2+}\) channels open, allowing calcium ions to rush into the terminal.
3
\(\text{Ca}^{2+}\) triggers vesicle fusion with the presynaptic membrane (exocytosis).
4
Neurotransmitters diffuse across the synaptic cleft.
5
Neurotransmitters bind to receptors on the postsynaptic membrane, opening ion channels.
6
Signal is terminated via reuptake, enzymatic degradation, or diffusion away.

The Critical Role of Calcium

Calcium ions (\(\text{Ca}^{2+}\)) are the essential trigger for neurotransmitter release. When an action potential reaches the axon terminal, voltage-gated calcium channels open. The influx of \(\text{Ca}^{2+}\) causes synaptic vesicles to fuse with the presynaptic membrane and release their contents into the cleft.

Action Potential
\(\text{Ca}^{2+}\)
Influx
 Vesicle Fusion (Exocytosis)

Excitatory vs Inhibitory Signals

Excitatory (EPSP)
Depolarizes the postsynaptic membrane, bringing it closer to threshold. Makes the neuron more likely to fire. Example: \(\text{Na}^+\) channels opening.
Inhibitory (IPSP)
Hyperpolarizes the postsynaptic membrane, moving it further from threshold. Makes the neuron less likely to fire. Example: \(\text{Cl}^-\) channels opening.

Temporal and Spatial Summation

Temporal Summation
Multiple signals from the same presynaptic neuron arrive in rapid succession, accumulating to reach threshold.
Spatial Summation
Signals from multiple different presynaptic neurons arrive simultaneously and combine at the postsynaptic cell.

Major Neurotransmitters

Neurotransmitter Type Key Functions
Acetylcholine (ACh) Excitatory/Inhibitory Muscle contraction, memory, attention
Dopamine Excitatory/Inhibitory Reward, motivation, motor control
Serotonin Inhibitory (mostly) Mood, sleep, appetite, pain
GABA Inhibitory Main inhibitory NT of the brain
Glutamate Excitatory Main excitatory NT of the brain
Norepinephrine Excitatory Alertness, fight-or-flight response

How Signals Are Terminated

After neurotransmitters have done their job, the signal must be stopped to prevent continuous stimulation. Three main mechanisms accomplish this:

Reuptake
The presynaptic neuron reabsorbs the neurotransmitter using transporter proteins. This is the target of many antidepressant drugs (SSRIs).
Enzymatic Degradation
Enzymes in the cleft break down the neurotransmitter. Example: acetylcholinesterase breaks down ACh.
Diffusion
Neurotransmitter molecules drift away from the cleft and are absorbed by surrounding glial cells.

How to Analyze a Synapse Problem

1
Identify the neurotransmitter involved and whether it is excitatory or inhibitory.
2
Trace the signal path: presynaptic terminal, cleft, postsynaptic receptors.
3
Determine the postsynaptic effect: EPSP (depolarization) or IPSP (hyperpolarization)?
4
Consider signal termination: Is reuptake, degradation, or diffusion being affected?
5
Predict the outcome: How would blocking or enhancing any step change the response?

Example: Acetylcholine at the NMJ

At the neuromuscular junction (NMJ), a motor neuron releases acetylcholine (ACh) to trigger muscle contraction. Let's trace the full process:

1
An action potential travels down the motor neuron's axon to the presynaptic terminal.
2
\(\text{Ca}^{2+}\) enters through voltage-gated channels, triggering vesicle fusion and ACh release.
3
ACh binds to nicotinic receptors on the muscle fiber, opening \(\text{Na}^+\) channels (EPSP).
4
Acetylcholinesterase rapidly degrades ACh in the cleft, terminating the signal.

Example: How SSRIs Work

Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly prescribed antidepressants. They work by altering synaptic transmission of serotonin.

Normal Presynaptic Reuptake Postsynaptic Less serotonin available With SSRI Presynaptic Blocked Postsynaptic More serotonin available

Example: Nerve Agents and AChE

Nerve agents (such as sarin) are deadly because they inhibit acetylcholinesterase (AChE), the enzyme that breaks down acetylcholine at the neuromuscular junction.

1
AChE is blocked: the enzyme cannot degrade ACh in the synaptic cleft.
2
ACh accumulates: receptors are continuously stimulated, causing sustained muscle contraction.
3
Result: Paralysis, respiratory failure, and potentially death due to inability to relax the diaphragm.

Common Mistakes

✕ Confusing Direction
Signals only travel in one direction across a chemical synapse: from presynaptic to postsynaptic. The signal cannot go backwards.
✕ All NTs Are Excitatory
Many neurotransmitters are inhibitory (e.g., GABA). Some, like dopamine, can be either depending on the receptor type.
✕ NTs Cross the Membrane
Neurotransmitters do not enter the postsynaptic cell. They bind to receptors on the surface, which then open or close ion channels.

Summary Comparison

Feature Chemical Synapse Electrical Synapse
Speed Slower (0.5 to 5 ms delay) Nearly instantaneous
Direction Unidirectional Bidirectional
Mechanism Neurotransmitter release Gap junctions (ion flow)
Modifiability Highly modifiable Limited modifiability
Amplification Yes (signal can grow) No (signal weakens)
Prevalence Most synapses in CNS Cardiac muscle, some CNS

Question 1 of 5

What ion must enter the presynaptic terminal to trigger the release of neurotransmitters from synaptic vesicles?

Question 2 of 5

GABA is best described as the brain's primary:

Question 3 of 5

An SSRI works by blocking the reuptake of serotonin. What is the immediate effect at the synapse?

Question 4 of 5

A toxin blocks voltage-gated calcium channels on the presynaptic terminal. What would happen?

Question 5 of 5

Which process describes multiple signals from different presynaptic neurons arriving simultaneously to collectively depolarize a postsynaptic neuron?