Signal Transmission

How are signals transmitted in the nervous system?

Neurons send and/or receive signals. This process is very similar regardless of whether signals are sent to a neuron, muscle, or gland cell. However, neuron-to-neuron transmissions (communications) are by far the most numerous.

Electrical transmission occurs where cells are in direct contact. An action potential causes depolarisation of the presynaptic cell membrane followed immediately by a depolarisation of the postsynaptic cell membrane. This transmission of information is very fast and always excitatory (depolarising).

In contrast, chemical transmission occurs where neurotransmitter molecules diffuse across a narrow region of extracellular space from the presynaptic terminal to the postsynaptic terminal. The binding of transmitters may excite (depolarise) or inhibit (hyperpolarise) the postsynaptic cell. The strength of this connection may be finely tuned. In other words, it provides the system with more control.

An electrical synapse is made by a gap junction. A gap junction is a set of pores on both membranes that may be open. They are aligned opposite each other such that when an action potential (depolarisation) arrives at a gap junction on one cell, the action potential continues directly across the membranes into the next cell, e.g. a post-synaptic neuron. They are well suited for the regulation of rhythmic or synchronised electrical activity such as breathing.

A chemical synapse is made by neurotransmitters and receptors. The presynaptic terminal (where neurotransmitters are released) is not directly connected to the postsynaptic terminal (e.g., where one of many mushroom shaped spines are attached to the postsynaptic neuron). The terminals are separated by an extremely narrow slice of extracellular space known as a synaptic cleft.

Chemical synapses are far more common than electrical synapses in mammals.

Image: Purves et al, 2001.

The synaptic cleft (for chemical transmission) is approximately 20 nm wide (20 x 10^-9 m). The presynaptic terminal manages pools of synaptic vesicles which contain neurotransmitters. All neurotransmitters have a similar life cycle (1) synthesis, (2) storage, (3) release, (4) binding, and (5) inactivation. Here are some common neurotransmitters.

•  Small molecules: acetylcholine.  
•  Monoamines:  dopamine,  norepinephrine (aka, noradrenaline), epinephrine,  serotonin (5-HT),  and histamine.   
•  Amino acids:  glutamate and g-aminobutyric acid (GABA).  
•  Large molecules: neuropeptides -- over 50 kinds have been isolated in nerve cells.   For example,  Substance P and enkephalins, which are active during inflammation and pain transmission in the PNS, and endorphins, which are endogenous opiates that produce euphoria, suppress pain, or regulate response to stress.

Other transmitters include kainate and adenosine triphosphate (ATP).

Signal transmission may be divided into three regions.
1.  Presynaptic terminal

The local depolarisation causes Ca2+ channels to open. Ca2+ rushes into the presynaptic cell via voltage gated calcium channels because the Ca2+ concentration is much greater outside the cell than inside. Ca2+ ions bind to calmodulin and this causes vesicles filled with neurotransmitter to migrate towards the presynaptic membrane. When the vesicle merges with the presynaptic membrane it forms a continuous membrane such that the neurotransmitter is released into the synaptic cleft (exocytosis).

2.  Synaptic Cleft

Neurotransmitter molecules diffuse across the synaptic cleft and bind to receptors. The time period from neurotransmitter release to postsynaptic receptor channel binding is less than a millisecond.

3. Postsynaptic terminal

After the neurotransmitters bind to the postsynaptic receptors, positive ions (sodium and calcium) rush in an depolarise this patch of membrane.  The summation of positive currents flowing in via this and other synapses located on its dendritic tree and soma may cause the membrane potential to increase to the point where the postsynaptic neuron fires an action potential.

Image: Purves et al, 2001.

To simplify matters, the terminals can be viewed as resource managers.   The presynaptic terminal manages pools of vesicles, presynaptic ligand gated receptors (such as preNMDARs) and voltage gated calcium channels, and many other things.   Meanwhile the post-synaptic terminal manages, for example,  the number and location AMPA, NMDA, P2X, and other receptors on its membrane.

There are many types of receptors at various synaptic and extra-synaptic locations, i.e. on both neurons, and on the astrocyte that enwraps the synaptic cleft. Furthermore, the quality and quantity of receptors varies greatly, even within the same brain region and same type of neuron.

Synaptic plasticity may be implemented in the pre- and/or post-synaptic terminal ( and in other locations? ).    First, the probability of vesicle release from the presynaptic terminal may be increased/decreased (possibly due to higher/lower calcium levels).   Second, the postsynaptic terminal could change the number and/or quality of receptors on its membrane.   The resulting changes may be short term or long term.   The details of how synapses implement plasticity are complicated ... they will be the subject of future posts.