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Transmission of Nerve Impulses

The human brain contains billions of neurons (nerve cells) arranged in a gigantic network (artist's impression, right). The neurons in this network communicate with each other by transmitting nerve impulses (signals) from one neuron to another. The process by which this is done is very complicated but surprisingly well understood.

This project discusses how this transmission is carried out.

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neural network

STAGE A: Synaptic Transmission

As already mentioned, synaptic transmission is the process that lets a nerve impulse pass from one neuron to the next across the synaptic gap (or just synapse). It is the first of the three steps in the transmission of a nerve impulse.

Synaptic transmission is a chemical transmission effected by neurotransmitters. A neurotransmitter is a molecule that moves across the synapse and, by binding (attaching) to a receptor on the post-synaptic neuron, influences its probability of firing. Variations in the amount of neurotransmitters released, the kind and number of receptors available affect the transmission of impulses.

Transmission begins when an electrical impulse travelling along an axon reaches the pre-synaptic membrane at the terminal button (i.e. the 'bump' at the end of the axon). Neurotransmitters are released, which move across the synapse and activate the receptors on the post-synaptic membrane of a dendrite (or, in a few rare cases directly onto the soma for pre-synaptic neurons that connect to the soma rather than to a dendrite). Transmission occurs dozens of times per second at the synapse of each neuron, a process that occurs in each of our billions of brain neurons.

Ion channels

We have mentioned that a neuron membrane contains leakage channels which are open all the time. Membranes also have two other kinds of ion channels, as follows:

Ligand (or binding) ion channels: These channels are normally closed, but open when a neurotransmitter binds to the channel. The channel then allows ions to enter. See the diagram on the below.

Voltage-gated (or voltage-sensitive) channels: These channels are sensitive to a change in voltage. Normally they are closed but open when affected by a voltage, allowing ions to pass through. Most of these channels are in the axons rather than the dendrites (we will learn a lot about them in Stage C).

It is these two kinds of channels that are involved in synaptic transmission. Note that the leakage channels are still present and still function (but are not shown in the diagram). However, as they are just 'leakage' channels. the number of ions that move through them is very small, whereas many ions move through the other two kinds of channels.

ligand ion channel

voltage- sensitive ion channel

Main steps in synaptic transmission by neurotransmitters

Chemical transmission takes place in the synapses between neurons, enabling nerve impulses to be transmitted from one neuron to the next. This process is called chemical transmission because the diffusion of chemical molecules from one neuron to the next is what enables an impulse to be reconstituted in that second neuron as an electrical impulse. Chemical transmission gives the brain the flexibility that is required for learning. The following are the main steps for synaptic transmission.

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ligand ion channel
Neurotransmitter molecules
voltage- sensitive ion channel

Step 1: Synthesis

The neurotransmitter is synthesised (made) in the terminal button of the axon from a precursor (i.e. a substance that is changed into another substance, in this case a neurotransmitter) using enzymes present in the axon.

(An enzyme is a substance that helps to speed up a chemical reaction without itself being changed.)

The neurotransmitters are then stored in

synaptic vesicles (a vesicle is a small fluid-filled container) in the terminal button of the axon. The most common neurotransmitter is the compound glutamate.

Step 2: Secretion

When a nerve impulse travelling down an





































axon (also called an action potential as




















labelled in the diagram on the right) reaches




















the terminal button, it causes the voltage-



















Ca2+ ion






sensitive Ca2+ channels to open, allowing






Na+ ion






many Ca2+ ions to enter the terminal



























button. This causes the synaptic vesicles to


















move down and merge with the cell































membrane, releasing neurotransmitters into
































the synaptic gap (the black dots represent the neurotransmitter molecules). The empty

vesicles then close up again and retreat inward, ready to be filled with neurotransmitters again.

Note: In this diagram, charges on the inner and outer layers of the membrane are shown. Remember that in a neuron at rest, the outer layer is positively charged (+) while the inner layer is negatively charged (-). To keep the diagram simple, only some of the charges are shown; the + charges actually go all the way around the outer layer and the – charges all the way around the inner layer.

Step 3: Binding

The neurotransmitters move across the synaptic gap and bind to receptors (ion channels) on the membrane of the post- synaptic neuron that are specific to that neurotransmitter. (In the diagram, the binding is shown by the small black dots – the neurotransmitters – sticking to the top of the receptors/ion channels.) This results in the ligand Na+ ion channels opening

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and letting in sodium ions.

The small diagrams (on the right) show an enlarged view of what happens. The red dot is the neurotransmitter molecule binding to the Na+ ion channel. Then Na+ ions enter.

We have said earlier, that in the rest state, the inside of a neuron is negative (as shown in the diagram for Step 1). But after the Na+ ions pour in, there are now more positive charges than negative charges so the inside layer of the membrane now has an overall positive charge, as the lower small diagram shows. Note: On the outer layer of the membrane there is actually almost no change in the charge as there are billions of Na+ ions outside, so the movement of a few inside the dendrite makes practically no difference. However, the outside layer is now relatively negative compared to the inner layer of the membrane. So after the entry of the Na+ ions, there is a reversal of charge as the lower small diagram shows.

Step 4: Inactivation

The neurotransmitters unbind from the membrane and return to the synaptic gap where they are quickly inactivated to allow the receptors (ion channels) to be available for the next stimulus. Neurotransmitters can be inactivated by one or a combination of the following processes:

(1)They simply diffuse out of synaptic gap and spread into the space outside the neurons,

(2)They are broken down into bits by enzymes present in the synaptic gap,

(3)They are reabsorbed by the terminal button of the pre-synaptic neuron and recycled into a vesicle (this is the case shown in the diagram, above right),

(4)They are removed from the synaptic gap and destroyed by one kind of glial cells (known as astrocytes).

Later, in Stage B, we will see that the Na+ ions that have entered the post-synaptic neuron diffuse further down into the dendrite and the soma. As they do so, the inside of the post-synaptic membrane returns to its negative state and is ready to receive the next signal that passes across the synaptic gap.

Extra: Electrical transmission across a synapse

Most synapses involve chemical transmitters as discussed above. But a few neurons involve electrical transmission across the synaptic gap. Some synapses are both electrical and chemical; at these, the electrical response occurs earlier than the chemical response.

An electrical synapse is often called a gap junction, in which the membranes of the two neurons are connected by channels that let the ions pass directly from one neuron to the other. Gap junctions allow for a more

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rapid communication. But we will not be concerned with these.

Chemical synapses are slower than electrical ones but are also far more flexible (without going into what this means). This valuable flexibility is the foundation of all learning.

Strengthening the transmission: AMPA and NMDA receptors

The chemical transmission across the synapse can be made stronger, which results in a stronger electrical signal travelling down the rest of the post-synaptic neuron. Strengthening happens in two ways:

1.By increasing the number of receptors (ion channels) in the post-synaptic membrane already discussed above. (These receptors/channels are called AMPA receptors,

which, for those interested, is short for α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid!!) Activation of this type of receptor allows Na+ ions to enter.

2.By using another type of receptor (called an NMDA receptor, which is short for N-methyl-D-aspartate). Activation of this second type of receptor allows calcium ions Ca2+ to enter in addition to sodium ions. Calcium ions, like sodium ions, are part of the mix of ions outside neurons. NMDA receptors are normally blocked by a magnesium ion (Mg2+) as shown in the diagram.

Both kinds of receptors are activated by glutamate neurotransmitter (red dots in above diagram) which binds to the receptors.

The AMPA receptor is only ligand gated, that is, it opens only when the neurotransmitter binds to it. The NMDA receptor however, is both voltage and ligand gated, that is, it depends on the inside of the membrane having a high enough positive charge (voltage) to eject the Mg2+ ion then binds with the neurotransmitter to allow ions to enter the neuron.

How the two kinds of receptors function depends on the strength of the stimulus/signal/nerve impulse (call it what you like!) arriving from the pre-synaptic neuron.

1.Weak stimulation: That is, when only a few neurotransmitters cross the synaptic gap. This normally activates just the AMPA receptors. This is because the Mg2+ ions at the core of the NMDA channels block these channel thus preventing ions from entering through them. AMPA channels do not have this Mg2+ ion. The diagrams below show what happens.

The AMPA receptor is shown in blue, the NMDA receptor in pink (with the Mg2+ ion blocking its pore). The neurotransmitter crosses the synaptic gap and binds to the AMPA receptor, allowing Na+ ions to enter. While they may also bind to the NMDA receptor (as shown in the third diagram), the Mg2+ ion remains in place.

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2.Strong stimulation: A strong stimulus occurs when there are lots of neurotransmitters or there is brief high-frequency stimulation (that is, signals in the pre-synaptic following each other in rapid succession). This makes the inside of the post-synaptic membrane much more positive, and causes the Mg2+ in the NMDA channel to be expelled. The NMDA receptor, along with the AMPA receptor, then responds to glutamate neurotransmitter admitting large amounts of Na+ as well as Ca2+. This is shown in the diagrams below.

The calcium ions (Ca2+) that enter the post-synaptic neuron activate certain substances (called protein kinases), which result in the formation of more AMPA receptors to the post-synaptic membrane (see the diagram on the right). Now that there are more receptors, the synapse has thus been strengthened, that is, it will respond more rapidly and more strongly (i.e. producing a stronger signal) to future releases of glutamate across the synaptic gap.

[The Ca2+ ions also seem to play a part in the formation of our long- term memories though detailed mechanisms of how this happens are not yet known.]

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Extension: Phosphorylation

Phosphorylation is the addition of phosphate ions (PO43-) to AMPA receptors already present in the neuron. It increases their conductance to sodium ions, that is, allows many more Na+ ions to enter. For more on this, go to the following website:

Look at slides 5 – 8 in particular which elaborate on this and also provide some animations.

Video animation

How transmission across a synapse occurs. Here are two of many video animations available on the web:

Note the use of terms not refereed to in this text: electrical impulse = action potential, vesicle = container/sac that holds neurotransmitter molecules) See also diagram at right.

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