Signal propagation: The movement of signals between neurons
Your brain is a hotbed of electrochemical activity. About 100 billion neurons are each firing off 5-50 messages (action potentials) per second. This activity allows you to process your environment, move your muscles, and even keep your balance! If you touch something slimy, that information goes from your fingertips to your brain, and then your brain says “eww, no!” and sends information to your fingertips telling them to move away. The same thing happens when you trip and you’re about to fall, or a bright light flashes in your eyes. Your brain receives information about where you are in space, or the brightness of the light, and responds accordingly. And it’s in our best interests that this action-reaction process goes quickly – so that we can catch ourselves as we fall, or shut our eyes tight. The process of sending these signals takes place in two steps: along the cell (action potential) and between cells (neurotransmitters).
Illustration of a complicated network of neurons.
How does information travel?
Information to and from the brain travels along neurons which are arranged in networks that let them pass information 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.
Illustration showing two neurons with an action potential traveling down one, and relaying a signal to the second axon.
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 it includes 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.
Illustration showing several pre and post synaptic neurons with the synaptic cleft highlighted, where neurotransmitters are released.
The Pre-Synaptic Cell
- Chemicals known as neurotransmitters are stored in membrane-bound vesicles at the axon terminal of neurons.
- Membrane proteins on the vesicles bind membrane proteins at the axon terminal to tether the vesicles in place.
- A protein known as complexin acts like a brake and stops 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.
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 signaling 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.
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.
Illustration showing details of a pre-synaptic cell and a post-synaptic cell.
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.
Want to join the conversation?
- Is there anyway to get the electrical signals and understand them ?(2 votes)
- Electrodes such as in an electroencephalogram (EEG) can be used to detect and record electrical activity. Commonly used in functional brain studies to determine how the brain responds to various stimuli.(3 votes)
- When neurotransmitters cross the synapse and activate the receptors, do Na ions from the pre-synaptic neuron cross the synapse as well? I am unsure of how an action potential is generated in the post-synaptic neuron.(2 votes)
- The action potential (AP) is generated in the same way as it was in the pre-synaptic neuron, i.e. graded potentials in the neuron generate enough change in the cell membrane voltage that the local cell membrane depolarises to the voltage AP threshold and generates an AP via influx of Na+.
The Na+ ions do not have to move between neurons along with neurotransmitters, as I believe the Na+/K+ pump channels on cells, including neurons, ensure a higher concentration of Na+ in the interstitial fluid (compared to the intracellular environment).(3 votes)
- When a AP reaches the axon terminal, how exactly does it communicate with the next neuron? Is it via the neurotransmitters? Also, once a new neuron receives the signal, is a new AP started or is it the same AP traveling across all the necessary neurons?(2 votes)
- When an AP reaches the axon terminal, it releases NT to convey either an excitatory or inhibitory graded potential to the post-synaptic cell. The binding of NT on the post-synaptic cell's receptors causes an influx of ions and thus if the ions are Na+, it will create a new AP.(2 votes)
- So if I'm understanding the article correctly then it takes multiple pre-synaptic cells to generate a gradient potential that is large enough to create an action potential. In turn, multiple of those action potentials from different neurons would be required to create an action potential in the next 'link in the chain' and stimulate the neuron to fire. So if each neuron needs, lets say, 10 potentials from pre-synaptic neurons to make it fire, then you would need 100 action potentials to send a signal down a 'chain' of three neurons; the 100 could stimulate 10, and then those 10 could stimulate 1. Does that make sense, and is that accurate? Basically it takes a LOT of stimulus to create a signal that goes all the way to the brain.(0 votes)
- Your ideas sound good, but its more complicated than what you make it out to be.
The pre-synaptic strength of the neuron does not dictate the post-synaptic strength of the neuron. It is plausible that the post-synaptic neuron only needs one signal to fire (imagine in the synapse was near the trigger zone) if the graded potential is above the threshold potential. Therefore, it is difficult to determine how many neurons will be required to convey a message.
If ten are required, then yes 10 synapses would be required to fire one neuron. But 100 may not be needed to activate those 10.(5 votes)
- I have a question that I'm curious about (and that I need for school) that I didn't find in the article. When signals move along neuronal axons, are they chemical or electrical messages? I know that I've heard this information before, however, I am unable to recall it. If anyone could give me a response regarding my inquiry, it would be greatly appreciated! Thank you in advance!(2 votes)
- If a neuron receives a weak excitatory stimulation and a strong inhibatory stimulation just around the same time, will the neuron fire?(1 vote)
- Is it safe to say that any chemical that destroys the membrane and vesicle proteins in neurotransmitter release would be considered an anesthetic?(1 vote)
- No, because an anesthetic causes a loss of sensation. In the example they used with botox, the membrane and vesicle proteins are destroyed which makes it impossible to move the muscles in that area. However, when someone receives botox, they have no change in sensation to that area.(1 vote)
- Isn't it true that new evidence has found that individual cells can actually signal with multiple neurotransmitters?(1 vote)