Chemical Synapses

Vertebrate nervous systems are composed of two principal cell types: glia and neurons. Glial cells are the most abundant and are involved primarily in maintaining ion homeostasis in the brain. Information processing is performed by neuronal cells that form intricate networks of processes capable of conducting and transferring electrical information at high speed and high efficiency. Neurons are elongated, polarized cells that extend two types of processes, called axons and dendrites. Axons are long and thin, and can be up to 1m in length.Dendrites are much shorter, tapered and highly branched processes often covered with small protrusions or thorns called dendritic spines. Contact sites between neurons (termed synapses: from the Greek ‘to clasp’) occur primarily between small swellings along axonal profiles, known as the presynaptic bouton, and the dendritic area of a target cell, termed the postsynaptic reception apparatus (postsynaptic junction). The extracellular space situated between the presynaptic and postsynaptic sides of these junctions is known as the synaptic cleft (Figure 1). While most presynaptic boutons can terminate on dendrites, they may also end on dendritic spines, the neuronal cell soma, the initial segment of an axon, called the axon hillock, or another presynaptic bouton. Each of these synapses has a specific name, such as axospinus, axodendritic, axoaxonic or even dendrodendritic, depending on whether the synapse is formed between an axonal presynaptic bouton, a spine, a segment of dendrite, another axon or between two dendrites, respectively. Synapses formed between the axon terminals of motor neurons and muscle cells are called neuromuscular junctions (NMJs) (Figure 2). (see Cells of the nervous system.) (see Neurons.) (see Axons.) (see Synapses.) Intraneuronal signalling, originating primarily in the dendritic arbour or the soma of neuronal cells, takes the formof electrical impulses or actionpotentialswhich travel down the axon to the presynaptic boutons. Interneuronal signalling, occurring at synapses, can be either electrical or chemical in nature. Electrical synapses allow a direct electrical coupling between neurons through small pores or channels, called gap junctions, present in the plasma membranes of both cells.When open, these junctions allow the free passage of ions and small molecules in either direction. While gap junctions are commonly found between nonneuronal cells, such as glia and epithelia, they are rarely found between vertebrate neurons. This is probably due to the limited ability of electrical synapses to be dynamically regulated, compared with chemical synapses (see below). (see Action potential: generation and propagation.) (see Electrical synapses.) As the name implies, signal transduction at chemical synapses involves the conversion of electrical signals that arrive at the presynaptic bouton into chemical signals that are perceived by the postsynaptic cell. As is discussed in detail below, these chemical signals or substances, called neurotransmitters, are released into the synaptic cleft by the presynaptic bouton, and act to initiate a second electrical signal in the postsynaptic cell by binding to, and opening, postsynaptic ligand-gated ion channels known as neurotransmitter receptors. Signalling across chemical synapses is mostly unidirectional and highly regulated, features that are essential for the establishment of complex highly plastic nervous systems. (see Neurotransmitters.) (see Neurotransmitter release from presynaptic terminals.) (see Neurotransmitter receptors in the postsynaptic neuron.) Clues to how chemical synapses enable interneuronal transmission came initially from high-resolution electron microscopy (EM) studies performed in the 1950s, and from electrophysiological studies. Ultrastructural studies revealed that central nervous system (CNS) synapses are asymmetrical cellular junctions composed of three morphologically distinct compartments: the presynaptic boutonfilledwith small clear synaptic vesicles (SVs), a synaptic cleft, and an electron-dense postsynaptic structure referred to as the postsynaptic density (PSD) (Figure 1). The presence of numerous SVs of uniform diameter (40– 60 nm depending on neuronal type) within presynaptic boutons suggested that SVs were the morphological correlate of physiological quanta of signalling information being measured by electrophysiological methods. This concept is supported by subsequent studies showing that SVs contain high concentrations of neurotransmitter (3000–5000 molecules per vesicle), whose fusion with the Article