Preparation: Synthesis and Storage
For uninterrupted synaptic function, neurotransmitters must be prepared in advance. A portion of the required pool is synthesized directly in the neuronal soma and delivered to the presynaptic terminal via axonal transport (at approximately 40 cm per day). Another portion is synthesized locally within the presynaptic terminal itself.
To prevent degradation in the cytoplasm and ensure rapid release, neurotransmitters are packaged into tiny membrane-bound spheres called synaptic vesicles. They are stored within the presynaptic terminal awaiting the arrival of a nerve impulse.
Key Steps of Signal Transmission
Information transfer in chemical synapses is strictly ordered and calcium-dependent. It involves the following steps:
- Arrival of the impulse. An action potential (AP) reaches the presynaptic terminal via the axon, causing membrane depolarization driven by $Na^+$ influx.
- Calcium influx. The voltage change opens voltage-gated calcium channels, causing $Ca^{2+}$ ions to rush into the terminal.
- Exocytosis. Calcium ions act as a key trigger: they cause vesicles to migrate to active zones of the presynaptic membrane, fuse with it, and release neurotransmitter quanta directly into the synaptic cleft.
- Diffusion and binding. Neurotransmitter molecules cross the cleft via passive diffusion and bind to specific protein-lipid receptors on the postsynaptic membrane.
Postsynaptic Response: Excitation and Inhibition
The interaction between the neurotransmitter and its receptors determines whether the signal propagates or is blocked.
In excitatory synapses, the neurotransmitter opens pores permeable to $Na^+$ ions. Sodium enters the cell, causing depolarization and generating an excitatory postsynaptic potential (EPSP) (amplitude 1–50 mV, duration 10–100 ms). Local currents from summated EPSPs generate a full action potential in adjacent membrane regions, propagating the excitation.
In inhibitory synapses (utilizing GABA, glycine, and in the autonomic system, certain receptors for acetylcholine and norepinephrine), membrane permeability increases for $K^+$ and $Cl^-$. Potassium leaves the cell while chloride enters along its concentration gradient. This leads to hyperpolarization and the development of an inhibitory postsynaptic potential (IPSP). The threshold increases, excitability drops, and signal propagation is blocked.
Neurotransmitter Clearance and Synaptic Properties
To prepare the synapse for the next signal, the synaptic cleft must be cleared of the spent neurotransmitter. This occurs via three mechanisms:
- Enzymatic degradation. Specific enzymes break down the neurotransmitter (e.g., acetylcholine is degraded by cholinesterase, while norepinephrine is degraded sequentially by COMT and MAO).
- Reuptake. Most degradation products or intact molecules are actively transported back into the presynaptic terminal for resynthesis.
- Diffusion and autoregulation. Some neurotransmitter diffuses away, while a portion binds to presynaptic autoreceptors that monitor release volume and provide feedback control.
These mechanisms underlie the key functional properties of synapses: unidirectional conduction (from pre- to postsynaptic membrane), high chemical sensitivity to biologically active agents, and synaptic delay caused by molecular release and diffusion.