Synapses

Main Types by Mechanism of Transmission

Based on the signal transmission mechanism, all synapses can be divided into two large groups:

1. Chemical synapses. This is the dominant type of contact in humans. The signal is transmitted via a specific chemical agent—a neurotransmitter. A key feature of this contact is strict unidirectional conduction. Molecules diffuse through the extracellular space and bind to target receptors, while reverse transmission is physically impossible.
2. Electrical synapses. These are relatively rare in the nervous system (e.g., in the retina). Cells are physically connected by tight junctions known as gap junctions (nexus). Ion channels pierce the membranes directly, uniting the cytoplasm of neighboring cells. This allows direct transmission of the depolarization wave. Similar structures exist in the myocardium and smooth muscle, but they connect muscle cells to each other and thus do not always fall under the strict definition of a synapse.

Structural Triad of a Chemical Synapse

A classical chemical synapse always consists of three mandatory components forming a single functional complex:

• Presynaptic terminal. As a rule, this is an expanded axon terminal. Inside it, vesicles filled with neurotransmitter are fixed to cytoskeletal elements. Voltage-gated calcium channels are embedded in the plasmalemma of this terminal and are tightly closed at rest.
• Synaptic cleft. A microscopic space 20–30 nm wide. Special filaments are located in this zone, mechanically weaving and holding both membranes together to prevent the contact from breaking apart.
• Postsynaptic membrane. This is a specialized region of the receiving cell's plasmalemma. It features a complex protein apparatus: specific neurotransmitter receptors, effector proteins (which execute the response), and enzymes whose task is to rapidly break down the spent neurotransmitter to terminate signal transmission.

Mechanism of Neurotransmitter Release

Signal transmission is triggered by the arrival of an electrical impulse at the axon terminal. The process occurs in several stages:

1. The excitation wave reaches the presynaptic membrane.
2. Voltage-gated $Ca^{2+}$ channels open, and calcium ions rush into the terminal.
3. A sharp spike in $Ca^{2+}$ concentration causes synaptic vesicles to detach from their anchoring cytoskeleton.
4. The vesicle membrane fuses with the presynaptic plasmalemma (exocytosis occurs).
5. A portion of the neurotransmitter is released into the synaptic cleft and begins to diffuse toward the target cell.

Ionotropic and Metabotropic Receptors

When the neurotransmitter reaches the postsynaptic membrane, the cell's response can develop along one of two pathways, depending on the receptor type:

• Ionotropic mechanism (fast). Here, the receptor molecule and the ion channel form a single protein complex. Upon neurotransmitter binding, the channel opens instantly. If it is a cation channel (as in nicotinic cholinergic synapses), $Na^+$ enters, causing depolarization and excitation. If it is an anion channel (GABAergic or glycinergic synapses), $Cl^-$ enters, causing hyperpolarization and inhibition.
• Metabotropic mechanism (slow). The receptor is not a channel. Neurotransmitter binding activates intracellular messengers that alter enzyme activity (usually protein kinases). This triggers the phosphorylation of targets in intracellular metabolism. In neurons, this ultimately leads to the opening or closing of channels, while in muscle cells, it can directly alter the activity of contractile proteins without changing the plasmalemma potential. This is how adrenergic synapses (norepinephrine) and muscarinic acetylcholine receptors operate.

Network Architectonics and Modulation

Neurons form complex networks thanks to divergence (the spread of a signal via axon collaterals to multiple cells) and convergence (the pooling of hundreds of contacts onto the soma of a single neuron). The cell sums up all incoming impulses and generates an integrative response.

In addition to classical synapses, nonsynaptic contacts exist. In this case, axon terminals have varicosities from which neurotransmitters (often neuropeptides or norepinephrine) are released directly into the wide intercellular space. This process is slow, but it exerts a generalized modulatory effect on an entire group of neighboring cells simultaneously, finely tuning their activity.