# Signal propagation: The movement of signals between neurons

## How does information travel?

Information to and from the brain travels along neurons which are arranged in networks that let them pass information along between the body and the brain. Here are the basics:
• Information is sent as packets of messages called action potentials
• Action potentials travel down a single neuron cell as an electrochemical cascade, allowing a net inward flow of positively charged ions into the axon.
• Within a cell, action potentials are triggered at the cell body, travel down the axon, and end at the axon terminal
• The axon terminal has vesicles filled with neurotransmitters ready to be released
• The space between the axon terminal of one cell and the dendrites of the next is called the synapse

## The synapse

The synapse is the space between the cell(s) sending the signal [the pre-synaptic cell(s)] and the cell(s) receiving the signal [the post-synaptic cell(s)]. The term “synapse” actually refers to the machinery required for information transfer, and include the pre- and post-synaptic membrane. The space between the cells is known as the synaptic cleft. For the purposes for our discussion here, we’ll talk about the synapse as if it is between only two neurons, but we’ll keep at the back of our heads that a single neuron can affect many post-synaptic neurons, and that each neuron is probably getting inputs from other cells all around it. Any neuron is both pre- and post-synaptic, depending on the synapse that we are looking at.

## The Pre-Synaptic Cell

• Chemicals known as neurotransmitters are stored in membrane-bound vesicles at the axon terminal of neurons
• Membrane proteins on the vesicle bind membrane proteins at the axon terminal to tether the vesicles in place
• A protein known as complexin acts like a brake, and stop the vesicles from fusing into the membrane and releasing their contents [remember: complexin complicates the process of vesicle fusion]
• The vesicle protein synaptotagmin can bind and release complexin in the presence of calcium
As the action potential travels down the axon, positive ions continue to flood the cell. Eventually, this influx reaches the very end of the neuron – the axon terminal. When this happens, the positive ions trigger voltage-gated calcium channels to open and let calcium ions into the cell. The calcium ions can then activate synaptotagmin to release the brake, and the vesicles fuse with the cell membrane, and the vesicle contents are released into the synaptic cleft.

## Neurotransmitters

Now we have these chemicals floating around between cells, so what? Neurotransmitters are how we communicate between one cell and the next. Synapses between neurons are either excitatory or inhibitory – and that all comes down to the neurotransmitter released. Excitatory neurotransmitters cause the signal to propagate - more action potentials are triggered. Inhibitory signals work to cancel the signal. Every time an action potential is triggered in a neuron, that cell will release whatever types of neurotransmitter it has, because calcium cannot tell the difference between one vesicle and another. So neurons tend to have only one type of neurotransmitter – either excitatory OR inhibitory.
• The major excitatory neurotransmitter is glutamate
• The major inhibitory neurotransmitter is GABA (gamma-aminobutyric acid)
• Other well-known neurotransmitters include dopamine, serotonin, adrenaline, and histamine
• Glutamate and GABA are released by nearly all the inhibitory or excitatory neurons of the brain, while specific neurotransmitters are found at precise points of the brain to help aid in learning, memory, motor function, and other neurologic functions.
• Some neurotransmitters also have other functions in different parts of the body (like adrenaline and the stress response, or histamine and allergies)
While this is the basic signalling method, there can be more nuance sometimes. Cells in the basal ganglia, for example, can release GABA and Substance P, but each neuron will always release both together, never just one or the other. This can help make the commands to the receiving cells more complicated, or reach a wider network of cells – both the ones that respond to GABA and the ones that response to Substance P.

## Post-Synaptic Cell

So how exactly is a neurotransmitter inhibitory or excitatory? This has to do with their interactions with the post-synaptic cell, the one that is being either excited or inhibited. The post-synaptic terminal are the dendrites and cell body of a cell. Dendrites are projections specially designed to create more surface area and receive more information.
• The post-synaptic terminal is full of neurotransmitter receptors
• The neurotransmitter receptors are, for the most part, ligand-gated ion channels, that open in response to being bound by the neurotransmitter they are specific for
• Whether a neurotransmitter is excitatory or inhibitory depends on the type of channel they open – excitatory neurotransmitters bind channels that let in positive ions like Na$^+$, inhibitory neurotransmitters open up Cl$^-$ channels
• Some receptors set off a signal cascade when activated, and lead to the transcription of new proteins or the insertion of more receptors into the cell membrane
Each vesicle packet released from the pre-synaptic neuron will contain a set amount of neurotransmitters, which will then bind to some of the receptors on the post-synaptic cell. If the neurotransmitter is excitatory, the influx of positive ions will depolarize (bring closer to zero) the cell body. If the neurotransmitter is inhibitory, it will hyperpolarize the cell body. However, a single vesicle of neurotransmitter isn’t enough to depolarize the cell body. Most of the time, all the vesicles released from an action potential aren’t enough to trigger an action potential in the following cell. This is why the brain uses neuron networks to send many signals to a single cell, or why a neuron may have to fire a couple times before it can pass the message along. There might even be competition among the neurons, with a single post-synaptic neuron receiving glutamate from one pre-synaptic neuron and GABA from its neighbor. The post-synaptic cell will only send the message along if it gets enough excitatory input to depolarize across the threshold, and open the voltage-gated ion channels in its axon.

## Consider the following

One good way to learn about this process is to understand what happens when it goes wrong. Botulism is caused by the bacteria Clostridum botulinum which secretes a chemical known as botulinum toxin that destroys the membrane and vesicle proteins involved in neurotransmitter release at the neuromuscular junction – causing weakness and fatigue. With no vesicle fusion, muscle cells do not get the signal to move. Botulinum toxin is the major ingredient of Botox, which is used in cosmetic procedures.