Contents
Introduction
Synapses are specialised junctions between neurones and other neurones (and between neurones and other cells in some definitions). They permit signals to be passed between the cells that form the synapse.
The function of neurones is based around electrical activity but synapses are not actually electrical junctions or relays. Instead, synapses transmit their signal using chemicals. As a result synapses relay the signal in one direction only.
Basic Structure and Function of a Synapse
Synapses have three main components, the
presynaptic terminal, the
post synaptic membrane and the
synaptic cleft. The last of these is simply the space between the presynaptic terminal and post synaptic membrane and is part of the extracellular fluid.
The presynaptic terminal is formed by a specialised expansion of the end of the axon of the neurone that is forwarding the signal on to the next cell. The postsynaptic membrane is part of the cell that is receiving this signal and is adapted to be able to detect and respond to the signal.
In simple terms the presynaptic terminal releases a chemical known as a neurotransmitter which diffuses across the synpatic cleft and binds to receptors on the postsynpatic membrane. These receptors are often ion channels that either depolarise or hyperpolarise the target cell when they open.
The neurotransmitters in the presynpatic terminal are stored in packets known as
synaptic vesicles. Many of these are held in a reserve pool, a few are in a state of being recycled and a few are docked to the membrane of the presynaptic terminal. The synaptic vesicles and their associated proteins are generated in the cell body of the neurone and transported to the axon terminal by axonal transport. The neurotransmitters themselves can be synthesised either in the cell body or the presynpatic terminal. Local synthesis is vital in order to enable the neurone to maintain the supply of neurotransmitters at the synapse.
The trigger for the release of synaptic vesicles is the arrival of an action potential at the presynaptic terminal. The depolarisation of the action potential causes voltage-gated calcium channels to open in the membrane of the presynaptic terminal. The opening of these channels permits an influx of calcium into the terminal. This influx causes the membranes of some of the docked vesicles to fuse with the membrane of the presynaptic terminal, thus discharging their contents into the synaptic cleft. The neurotransmitters then diffuse across the cleft, bind to the receptors on the postsynpatic terminal and exert their effect.
In order for the signals to be clear and crisp at the synapse the neurotransmitter needs to be removed quickly from the synaptic cleft. This can be achieved by enzymes that break down the neurotransmitter (such as acetylcholine and acetylcholinesterase), reuptake of the neurotransmitter by other receptors on the presynaptic neurone, clearance of the neurotransmitter by astrocytes or natural rapid degradation of the molecule due to its intrinsic instability (nitric oxide).
Neurotransmitters
Neurotransmitters are the chemicals that relay the signal from the presynaptic terminal to the postsynaptic terminal. They are typically simple molecules which can be easily and quickly synthesised and produced in large quantities.
The effect a neurotransmitter has on the postsynaptic target will depend upon the type of receptor that is expressed by that target. It is common for several different subtypes of receptors to exist for each neurotransmitter, each of which can produce a different response in the target cell. For example, the nicotinic receptors for acetylcholine open sodium gated ion channels, whereas the muscarinic receptors activate G proteins. In general receptors that are coupled to ion channels produce short, sharp responses in the target cell, such as contraction of skeletal muscle or the generation of an action potential in a neurone, while receptors which are linked to G proteins and other second messenger systems induce less rapid, more protracted responses that may ultimately result in long term modifications of function if the stimulation is repeated.
Acetylcholine was the first neurotransmitter to be discovered. It is important in the autonomic nervous system, at the neuromuscular junction and in a few pathways in the brain, some of which connect many neurones. However, within the brain, the amino acid glutamate is an important excitatory neurotransmitter (one that causes the postsynaptic cell to depolarise). Glutamate exerts this effect through AMPA receptors, with more complex actions being mediated by NMDA receptors. The main inhibitory neurotransmitter in the brain is GABA (gamma amino butyric acid). GABA inhibits neurones by binding to the GABA-A channel, which is a chloride ion channel. Opening of this channel allows an influx of chloride ions into the neurone. Alcohol augments the effects of GABA on GABA-A receptors. Glycine takes over much of the role of an inhibitory neurotransmitter in the spinal cord.
Other neurotransmitters include dopamine, adrenaline, noradrenaline and 5-hydroxytrypatmine (serotonin).
The traditional theory was that each neurone released only one type of neurotransmitter, no matter how many terminals its axon divided into. This remains essentially true, although is modified by the phenomenon of co-transmission.
The workhorse neurotransmitters are simple molecules that can be rapidly syntheised and recycled. A neurone can fire up to one thousand times per second, so it needs to be able to keep its presynaptic terminals well stocked. However, more complex peptide neurotransmitters also exist. These are released in parallel with the conventional neurotransmitters under specific circumstances, usually particular patterns of neuronal activity, when they can modify the response of the post synaptic neurone. Variation in the rates and patterns of neuronal firing can encode additional information in the brain and cotransmission is one way by which this electrical activity can be encrypted at the synapse.
All neurones are believed to release the same single neutrotransmitter, or combinations of neurotransmitters, at all of their axon terminals. Neurones may be described by the neurotransmitter they release and this leads to terms such as GABAergic neurones and cholinergic neurones.