Neurobiological Mechanisms of Synaptic Transmission

Information Transfer at Synapses

1. Action Potential and Depolarization

When an action potential reaches the synaptic terminal (Synapsenendknöpfchen), it depolarizes the membrane due to the opening of sodium ion channels. This process is similar to typical action potentials where sodium ions ($Na^+$) flow into the neuron. Within the synaptic terminal, in addition to sodium channels, there are voltage-gated calcium ion channels. At the time of depolarization, these channels also open. Notably, the concentration of calcium ions ($Ca^{2+}$) in the synaptic cleft is up to 500 times higher than that inside the neuron, prompting the immediate influx of calcium ions through the opened channels. The extent of this calcium influx is directly related to the number of incoming action potentials.

As $Ca^{2+}$ concentration increases, it serves as a signal for vesicles within the synaptic terminal. A higher concentration of calcium ions correlates with a greater number of vesicles fusing with the presynaptic membrane. This fusion, a process known as exocytosis, results in the release of neurotransmitters—specifically, thousands of acetylcholine ($ACh$) molecules per vesicle—into the synaptic cleft. The release of acetylcholine is meticulously controlled and occurs extremely rapidly; for instance, in the giant axon of the squid, it happens within 0.2 milliseconds after calcium channels are opened.

2. Diffusion of Acetylcholine and Postsynaptic Potential

Once released, acetylcholine molecules diffuse across the synaptic cleft to bind with specific acetylcholine receptors on the postsynaptic membrane. These receptors are ligand-gated ion channels that facilitate the permeability of the membrane to sodium ions ($Na^+$). Upon acetylcholine binding, these sodium channels open, allowing sodium ions to flow into the postsynaptic neuron. The influx of sodium ions depolarizes the neuron at the postsynaptic membrane, creating a postsynaptic potential (PSP). The magnitude of this depolarization is contingent upon the quantity of incoming sodium ions, which is influenced by the number of sodium channels activated by acetylcholine. If the postsynaptic potential surpasses a certain threshold, a new action potential is generated at the axon hillock of the postsynaptic neuron.

3. Recycling of Acetylcholine and Closure of Ion Channels

For another synaptic signal transmission to occur, the ion channels in the postsynaptic membrane must be closed. This closure is achieved by the rapid inactivation of acetylcholine, primarily mediated by the enzyme acetylcholinesterase. This enzyme breaks down acetylcholine into choline and acetate, thus inactivating the receptors and leading to the closure of the sodium ion channels. Choline then diffuses back to the presynaptic terminal, where it is reabsorbed through an active transport system. In the synaptic terminal, acetylcholine is resynthesized by combining choline with an acetate group, and new vesicles are formed and reloaded with acetylcholine.

Summary of Key Terms:

• Exocytosis: Process of releasing substances from the intracellular space to the extracellular space.
• Acetylcholine Esterase: Enzyme responsible for breaking down acetylcholine in the synaptic cleft to terminate its action.
• Postsynaptic Potential (PSP): The change in the membrane potential of the postsynaptic neuron due to ion flow through channels activated by neurotransmitters, leading to potential action generation.
• Active Transport System: Mechanism used to move choline back into the presynaptic terminal against its concentration gradient.