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4. Synaptic Transmission

A neuron is composed of three parts: cell body (soma), dendrites, and an axon. The cell body is similar to other types of cells, containing a nucleus and other typical organelles. The dendrites project from the cell body to receive signals from other neurons. The axon extends from the cell body to transmit signals to other neurons. When a nerve impulse is generated at certain region of a nerve membrane, it will propagate to other regions within the neuron. However, the nerve impulse cannot propagate to other neurons because there is a gap between two neurons. This gap is known as "synapse" (Figure 4-1).

In most cases, a synapse is formed between an axon terminal and a dendritic spine (a small protrusion from the dendrite). An axon may have one or more terminals. A dendrite typically contains many spines. Therefore, a single neuron can make several thousands of connections with other neurons.


Figure 4-1. Connections between axon terminals and dendrites.
[Source: NIH]

Signal transmission through the synapse is mediated by a class of small molecules called neurotransmitters. At the axon terminal, neurotransmitters are stored in vesicles. When the nerve impulse arrives, membrane depolarization will open voltage-gated calcium channels for the entry of Ca2+ ions, which then induce the release of neurotransmitters from the vesicles. Subsequently, the neurotransmitters diffuse through the synaptic cleft (about 200 - 500 Å wide) to bind with their receptors in the dendritic spine of a postsynaptic neuron (Figure 4-2).


Figure 4-2. Synaptic transmission is mediated by neurotransmitters.
[Source: Wikipedia]

The receptors for neurotransmitters can be classified into two categories: G-protein-coupled receptors and ionotropic receptors. Binding of neurotransmitters with G-protein-coupled receptors may trigger a cascade of signaling processes. The ionotropic receptors can form a ligand-activated ion channel whose activation (opening) depends on the binding of specific neurotransmitters. Major neurotransmitters are shown in Figure 4-3. The receptors for dopamine belong to G-protein-coupled receptors. Most serotonin (5-HT) receptors are also G-protein-coupled receptors. Receptors for the other neurotransmitters can form ion channels.


Figure 4-3. Chemical structures of major neurotransmitters.

Upon activation, some ligand-activated ion channels cause the postsynaptic membrane to depolarize while others lead to membrane hyperpolarization, depending on whether they conduct cations or anions. The GABA and glycine receptor channels conduct mainly chloride ions (Cl-). As a result, the entry of negatively charged Cl- ions cause hyperpolarization. Acetylcholine and glutamate receptor channels conduct cations such as Na+ and/or Ca2+. Their activation will result in depolarization.

In the postsynaptic neuron, the membrane voltage change at spines will propagate along the membrane to other regions. Since a neuron contains many spines and each spine may cause membrane voltage change, the membrane voltage at any region is determined by the summation of these membrane voltage changes when they reach the region. If the membrane is depolarized above the threshold, the action potential may be generated at the region. Typically, the action potential is initiated at the axon initial segment (AIS) - a short segment at the junction between the cell body and axon. AIS contains high density of voltage-activated Na+ and K+ channels (Grubb and Burrone, 2010).

Depolarization has positive, while hyperpolarization has negative, effects on the generation of action potentials. For this reason, the depolarization potential at spines is often called "excitatory postsynaptic potential" (EPSP) whereas the hyperpolarization potential is referred to as "inhibitory postsynaptic potential" (IPSP).

NMDA receptor (NMDAR) and AMPA receptor (AMPAR) play crucial roles in learning and memory. In the literature, NMDAR or AMPAR often refers to the whole ion channel, not the individual subunit. Both NMDAR and AMPAR are composed of four subunits. Each subunit belongs to the glutamate receptor family, which binds to the glutamate molecule (Traynelis et al., 2010). NMDAR is made up of the subunits that also bind to the NMDA molecule whereas AMPAR comprises the subunits that can also be activated by the AMPA molecule. The structure of AMPAR has been determined by x-ray crystallography (Figure 4-4).


Figure 4-4. The x-ray structure of AMPA receptor.