Table of Contents
Chemical Synapses: The Basic Principle
When excitation passes from one excitable cell to another (for example, from one neuron to the next, or from a neuron to a muscle cell), this usually happens at a specialized contact site: the synapse. At most synapses, the signal is converted from an electrical signal (action potential) into a chemical signal (neurotransmitter), and then back into an electrical signal in the target cell.
A typical chemical synapse consists of:
- Presynaptic cell: the “sending” cell, usually a neuron
- Synaptic terminal (axon terminal): the end of the presynaptic neuron
- Synaptic vesicles: membrane-bound vesicles in the terminal, filled with neurotransmitter
- Synaptic cleft: the narrow gap between cells (ca. 20–40 nm wide)
- Postsynaptic membrane: membrane of the “receiving” cell, rich in neurotransmitter receptors
The direction of information flow in most chemical synapses is fixed: from presynaptic to postsynaptic cell. This one-way conduction contributes to the directionality of information flow in nervous systems.
Sequence of Events at a Chemical Synapse
- Arrival of the action potential
- An action potential travels along the presynaptic axon and reaches the synaptic terminal.
- The membrane of the terminal depolarizes.
- Opening of voltage-gated Ca²⁺ channels
- Depolarization opens voltage-gated calcium channels in the presynaptic membrane.
- Ca²⁺ ions flow into the terminal down their electrochemical gradient.
- Vesicle fusion and neurotransmitter release
- Increased cytosolic Ca²⁺ triggers synaptic vesicles to move to and fuse with the presynaptic membrane (exocytosis).
- Neurotransmitter molecules are released into the synaptic cleft.
- Diffusion and binding to postsynaptic receptors
- Neurotransmitter diffuses across the cleft.
- It binds to specific receptors in the postsynaptic membrane.
- Often these receptors are ligand-gated ion channels: binding of transmitter opens the channel.
- Generation of postsynaptic potential
- Ion channels in the postsynaptic membrane open (or sometimes close), altering membrane permeability.
- Depending on the ions involved, the postsynaptic membrane becomes:
- Depolarized (more positive inside): excitatory effect
- Hyperpolarized (more negative inside): inhibitory effect
- Termination of the signal
- To prevent continuous stimulation, the neurotransmitter must be removed or inactivated:
- Enzymatic breakdown in the cleft (e.g. acetylcholine by acetylcholinesterase)
- Reuptake into the presynaptic terminal (or surrounding glial cells) via transporters
- Diffusion away from the synaptic cleft
- Vesicle recycling
- Portions of presynaptic membrane are retrieved by endocytosis to form new vesicles.
- These are refilled with neurotransmitter for subsequent release.
Excitatory and Inhibitory Synapses
Chemical synapses do not all have the same effect. They can make the postsynaptic cell more or less likely to fire an action potential.
Excitatory Synapses
- Neurotransmitter binding opens channels that usually allow Na⁺ (and sometimes Ca²⁺) to enter the cell.
- The membrane potential moves toward the threshold for an action potential.
- This local depolarization is called an excitatory postsynaptic potential (EPSP).
- EPSPs are usually:
- Small in amplitude (a few mV)
- Graded (their size depends on the amount of neurotransmitter)
- Short-lived
Inhibitory Synapses
- Neurotransmitter binding opens channels that:
- Let Cl⁻ enter the cell, or
- Let K⁺ leave the cell.
- The membrane becomes more negative inside (hyperpolarized) or stabilized near a negative potential.
- This is an inhibitory postsynaptic potential (IPSP).
- IPSPs make it less likely that the postsynaptic cell reaches threshold.
Whether a synapse is excitatory or inhibitory depends primarily on:
- The neurotransmitter used
- The receptor type and ion channels it controls, not just the identity of the presynaptic neuron
Summation: How Postsynaptic Cells Decide
A single EPSP is usually not enough to trigger an action potential. Instead, the postsynaptic neuron continuously “adds up” all incoming signals.
Spatial Summation
- Multiple synapses on different parts of the postsynaptic neuron are active at roughly the same time.
- EPSPs generated at different locations on the neuron can add together.
- If several excitatory synapses are active simultaneously, the combined depolarization may reach the threshold at the axon hillock (the usual trigger zone).
- IPSPs can cancel or reduce nearby EPSPs.
Temporal Summation
- A single synapse is activated repeatedly in rapid succession.
- Each EPSP arises before the previous one has completely decayed.
- The EPSPs can add up over time to reach threshold.
- High-frequency stimulation of an inhibitory synapse can similarly enhance inhibition.
Integration at the Axon Hillock
- The axon hillock contains a high density of voltage-gated Na⁺ channels and acts as a decision point.
- It integrates:
- All EPSPs and IPSPs from thousands of synapses
- Their timing and location
- If the membrane potential at the axon hillock reaches threshold, a new action potential is generated and conducted along the axon.
- If it does not, no action potential is produced.
Thus, the postsynaptic neuron functions as an integrator of synaptic inputs, “deciding” whether to pass on excitation.
Types of Chemical Synapses by Function
Axodendritic, Axosomatic, Axoaxonic
The site of contact influences the effect of the synapse:
- Axodendritic synapses: axon terminals on dendrites; usually excitatory.
- Axosomatic synapses: axon terminals on the cell body; often have strong influence, frequently inhibitory.
- Axoaxonic synapses: axon terminals contacting another axon’s terminal; can modulate the amount of neurotransmitter released (presynaptic inhibition or facilitation).
Fast vs Slow Synaptic Transmission
- Fast synapses:
- Use ionotropic receptors (ligand-gated ion channels).
- Response begins within milliseconds and is short-lived.
- Typical for rapid signaling (e.g. motor control).
- Slow synapses:
- Use metabotropic receptors (G-protein-coupled receptors).
- Activation triggers intracellular signaling cascades (second messengers).
- Effects develop more slowly but can last from seconds to minutes or longer.
- Often modulate excitability, sensitivity of ion channels, or gene expression.
Important Neurotransmitter Classes (Overview-Level)
Different synapses use different chemical messengers:
- Amino acid transmitters:
- Glutamate (main excitatory transmitter in vertebrate CNS)
- GABA and glycine (main inhibitory transmitters)
- Amines:
- Acetylcholine (e.g. neuromuscular junction, autonomic nervous system)
- Monoamines such as dopamine, serotonin, noradrenaline
- Neuropeptides:
- Short chains of amino acids (e.g. substance P, endorphins)
- Often co-released with classic transmitters; typically act via metabotropic receptors
Each transmitter can have different effects depending on the receptor types present on the postsynaptic cell.
Electrical Synapses (Gap Junctions)
In some cases, cells transmit excitation directly via electrical synapses:
- The membranes of the two cells are connected by gap junction channels.
- Ions and small molecules can pass directly from one cell to the other.
- Depolarization in one cell spreads almost instantly to the next.
- Properties:
- Very fast transmission
- Often bidirectional
- Useful for synchronized activity (e.g. some interneuron networks, some invertebrate axons, certain heart and smooth muscle cells)
Compared with chemical synapses, electrical synapses:
- Are less flexible (no transmitter choice, fewer modulation options)
- But are highly efficient for rapid, synchronized excitation
Modulation of Synaptic Transmission
Synapses are not rigid “wires”; their effectiveness can change over time and under different conditions.
Short-Term Changes
- Facilitation: repeated stimulation in quick succession increases transmitter release; later EPSPs become larger.
- Synaptic depression: high-frequency stimulation depletes vesicle stores; later EPSPs become smaller.
Long-Term Changes
Longer-lasting changes in synaptic strength underlie learning and memory (detailed in another chapter). Here it is enough to note:
- Long-term potentiation (LTP): persistent increase in synaptic strength after repeated strong activation.
- Long-term depression (LTD): persistent decrease in synaptic strength after certain patterns of activity.
Both involve changes on the presynaptic side (e.g. release probability) and/or postsynaptic side (e.g. receptor number, receptor sensitivity).
Influence of Drugs and Toxins
Many substances act specifically at synapses by:
- Mimicking neurotransmitters (agonists)
- Blocking receptors (antagonists)
- Inhibiting neurotransmitter breakdown
- Blocking reuptake
- Interfering with vesicle release or Ca²⁺ channels
While the details of psychoactive substances and neurotoxins belong elsewhere, it is crucial to recognize that synaptic transmission is a central target for such agents, which can dramatically change the transmission of excitation between excitable cells.
Synapses Onto Non-Neuronal Excitable Cells
Excitation is also passed from neurons to muscle cells and other excitable cells.
Neuromuscular Junction (Example)
- The presynaptic neuron is a motor neuron.
- The postsynaptic cell is a muscle fiber.
- Typically uses acetylcholine at nicotinic receptors (ionotropic).
- Binding of acetylcholine opens cation channels, leading to a strong EPSP (end-plate potential) that reliably triggers a muscle action potential and thus contraction.
Other examples include:
- Synapses from autonomic neurons to smooth muscle, cardiac muscle, and gland cells
- These often use a variety of transmitters and metabotropic receptors, adjusting the excitability and activity of target cells over a wide range.
By these mechanisms—chemical and electrical synapses, excitatory and inhibitory effects, summation and modulation—the nervous system and other excitable tissues achieve highly flexible, finely tuned transmission of excitation between cells.