Communication in the nervous system: transmission of a signal
Our nervous system controls everything we do: it is essential for our survival as individuals and as a species. It allows us to recognize danger and protect ourselves; to prepare food and nourish our bodies; to budget and make plans; and to create beautiful works of art. And it all runs on electricity - the flow of charged ions - and a little bit of chemistry! I am going to give a brief overview of how this communication system works, including how a signal originates, and how it is passed on.
As this subject is quite involved, and maybe too much to hit you with in one go, I will be splitting it up into two sections, Part I and Part II. Part I will bring us up to the generation of the initial signal, while Part II will focus on its onward propagation. Also, I have to warn you, although I've attempted to simplify this as much as possible, unless you have some biology background, there will be concepts and terminology here that will not be familiar. However, I don't think it's possible to break it down any further without it becoming tedious in the extreme, and the reader losing the will to live. For sure, this is the most ambitious essay that I've put together thus far, and may not be to everyone's liking. BUT! saying that, be brave and give it a go...you might love it!
As this subject is quite involved, and maybe too much to hit you with in one go, I will be splitting it up into two sections, Part I and Part II. Part I will bring us up to the generation of the initial signal, while Part II will focus on its onward propagation. Also, I have to warn you, although I've attempted to simplify this as much as possible, unless you have some biology background, there will be concepts and terminology here that will not be familiar. However, I don't think it's possible to break it down any further without it becoming tedious in the extreme, and the reader losing the will to live. For sure, this is the most ambitious essay that I've put together thus far, and may not be to everyone's liking. BUT! saying that, be brave and give it a go...you might love it!
Neurons: the building-blocks
The mammalian central nervous system (CNS) comprises the brain and spinal cord. The peripheral nervous system, or PNS, is everything else outside of these, while the autonomic nervous system (ANS) is not under our conscious control, and regulates visceral functions such as increasing or decreasing heart rate or modulating processes within the digestive system. All generate and pass on information the same way, however: the only differences are their anatomical location and their effector mechanisms (i.e., the target cell-type and its function). Therefore, as I will not be focusing on the final target, this essay will be relevant to all outposts of the nervous system.
Billions and billions of building-block units or specialized cells called neurons (along with other 'helper' cells), are the foundation of our nervous system. These are responsible for all movement, sensation, reflexes and (according to some neuroscientists) thought, emotions, memories, and even personality: for such tiny entities, they are pretty powerful.
This is a diagram of a neuron from the PNS (I attempted to do my own version, but after an hour and a half of TORTURE fiddling about with shapes and ClipArt in Word and Paint, I admitted defeat and decided to pillage Wikipedia instead. In my defence though, I did label it myself, so it is a little bit home-made!):
Billions and billions of building-block units or specialized cells called neurons (along with other 'helper' cells), are the foundation of our nervous system. These are responsible for all movement, sensation, reflexes and (according to some neuroscientists) thought, emotions, memories, and even personality: for such tiny entities, they are pretty powerful.
This is a diagram of a neuron from the PNS (I attempted to do my own version, but after an hour and a half of TORTURE fiddling about with shapes and ClipArt in Word and Paint, I admitted defeat and decided to pillage Wikipedia instead. In my defence though, I did label it myself, so it is a little bit home-made!):
There are three main parts to a neuron: the cell body or soma, the axon, and the axon terminal. The soma and branching dendrites collect and collate information from the surrounding environment before passing it on to the axon, where it is relayed to the axon terminal and on to the next neuron via the synaptic cleft (the junction between two neurons is known as a synapse - more about that in Part II!).
In the PNS, Schwann cells are a type of helper cell and act to produce the insulating myelin sheath that is found on most axons in mammals. There are gaps between the myelin covering, called the nodes of Ranvier. This is crucially important; the myelin causes the electrical signal to jump between the nodes, which exponentially expedites its transmission - up to 50 times faster, in fact. In the CNS, the myelin sheath is produced by a different kind of cell, called an oligodendrocyte. [Note: in certain disorders such as multiple sclerosis, the myelin sheath becomes degraded or scarred, leading to a massive slowing of transmission and extreme debilitation for sufferers. This illustrates the importance of the insulating layer, and the vital role played by the helper cells in optimizing nervous system functioning.]
Neurons can be broadly characterized as being sensory or motor, and those that communicate between the two (interneurons). In the simplest terms, sensory or input neurons collect information from multiple sources and pass it on to the CNS. Here, it is integrated with information from other sensory neurons, and processed, before being relayed to motor or output neurons, which induce a specific action that allows the individual to negotiate or interact in some way with his/her internal or external environment. For an individual to be aware of something, it must be perceived within the brain, which is the centre of consciousness. Therefore, the sensory input must reach the brain for us to experience a 'sensation' and react to it. However, sometimes there isn't time for this, and we can react 'without thinking': this is called a reflex, and is a primitive protective mechanism. In this scenario, the sensory input is relayed to the spinal cord - not the brain - and is directly passed on to motor outputs, so that a response can occur immediately (for example, when we rapidly close our eyes in response to a sudden, threatening movement in front of our faces).
In the PNS, Schwann cells are a type of helper cell and act to produce the insulating myelin sheath that is found on most axons in mammals. There are gaps between the myelin covering, called the nodes of Ranvier. This is crucially important; the myelin causes the electrical signal to jump between the nodes, which exponentially expedites its transmission - up to 50 times faster, in fact. In the CNS, the myelin sheath is produced by a different kind of cell, called an oligodendrocyte. [Note: in certain disorders such as multiple sclerosis, the myelin sheath becomes degraded or scarred, leading to a massive slowing of transmission and extreme debilitation for sufferers. This illustrates the importance of the insulating layer, and the vital role played by the helper cells in optimizing nervous system functioning.]
Neurons can be broadly characterized as being sensory or motor, and those that communicate between the two (interneurons). In the simplest terms, sensory or input neurons collect information from multiple sources and pass it on to the CNS. Here, it is integrated with information from other sensory neurons, and processed, before being relayed to motor or output neurons, which induce a specific action that allows the individual to negotiate or interact in some way with his/her internal or external environment. For an individual to be aware of something, it must be perceived within the brain, which is the centre of consciousness. Therefore, the sensory input must reach the brain for us to experience a 'sensation' and react to it. However, sometimes there isn't time for this, and we can react 'without thinking': this is called a reflex, and is a primitive protective mechanism. In this scenario, the sensory input is relayed to the spinal cord - not the brain - and is directly passed on to motor outputs, so that a response can occur immediately (for example, when we rapidly close our eyes in response to a sudden, threatening movement in front of our faces).
Where does the signal come from?
Now, we're getting down to it...this stuff isn't easy, and it took me ages to figure it out when I was first subjected to it, so we're in this together. As I said at the top, this is all about electricity and charged particles called ions. There are many ions floating around in our bodies, such as potassium (K+), sodium (Na+), and chloride (Cl-): these three are the most important for initiation and axonal propagation of the signal. Calcium (Ca2+) comes into its own at the synapse, for the transfer of the signal to a second neuron. Notice that all of these are positively-charged ions, apart from Cl-. This is important!
To backtrack a little, one of the most fundamental characteristics of mammalian cells is the fact that our cell membranes are semi-permeable. They are mainly composed of fats, and because "like dissolves like" (i.e., water-based solutions dissolve other water-based solutions, while fat-based solutions dissolve fat-based solutions), uncharged fat-soluble substances will move across the cell membrane far more readily than substances with a charge, such as ions. However! There are ways around this: little gateways are cunningly placed throughout the cell membrane, which can be activated by certain events to allow the passage of charged particles in or out of the cell. This is the basis of the resting membrane potential (RMP) and also, the action potential (AP), which forms the nervous system signal. So, how does it all work?
To backtrack a little, one of the most fundamental characteristics of mammalian cells is the fact that our cell membranes are semi-permeable. They are mainly composed of fats, and because "like dissolves like" (i.e., water-based solutions dissolve other water-based solutions, while fat-based solutions dissolve fat-based solutions), uncharged fat-soluble substances will move across the cell membrane far more readily than substances with a charge, such as ions. However! There are ways around this: little gateways are cunningly placed throughout the cell membrane, which can be activated by certain events to allow the passage of charged particles in or out of the cell. This is the basis of the resting membrane potential (RMP) and also, the action potential (AP), which forms the nervous system signal. So, how does it all work?
Origin of the resting membrane potential
The RMP is the overall charge across a cell (this can be actually be experimentally measured by placing one electrode inside the cell and a second one outside) and has been estimated to be -70mV in the neuron, meaning that there are far more negative ions inside the neuron than outside. This is maintained by the cell membrane preventing the free movement of ions across it, which supports an artificially-created ion gradient: nature adores equilibrium, and, if the cell membrane were freely-permeable, the charge across it would be 0, as the negative and positive ions would flow in and out until a balance was reached and everything was nice and neutral. Luckily for us, this is not the case!
This gradient is made possible by a transporter in the membrane called Na+/K+ ATPase. [As an aside, ATP is the energy currency of cells, derived from a series of reactions that convert glucose and oxygen to the waste products of carbon dioxide and water: it is the foundation of life, and fuels all of our body's processes. Interesting fact: The action of Na+/K+ ATPase utilizes 70% of the total ATP requirements of a neuron!]
This transporter uses the energy of ATP to drive Na+ and K+ across the cell membrane, against their concentration gradients [a concentration gradient refers to the relative amount of a diffusible substance in two connected spaces. Again, equilibrium is the desired result, with equal concentrations in both spaces]: for every three Na+ that it moves OUT of the cell, it brings two K+ INTO the cell, leading to a net deficit of positive charges inside the neuron. This deficit is further amplified by passive movement of these ions along their concentration gradient across the cell membrane (as the cell membrane is only semi-permeable, there is always some diffusion across: it's just slow and somewhat inefficient), as specific K+ channels facilitate greater outward movement of K+ than there is inward movement of Na+. So, effectively, this is the neuron at rest:
This gradient is made possible by a transporter in the membrane called Na+/K+ ATPase. [As an aside, ATP is the energy currency of cells, derived from a series of reactions that convert glucose and oxygen to the waste products of carbon dioxide and water: it is the foundation of life, and fuels all of our body's processes. Interesting fact: The action of Na+/K+ ATPase utilizes 70% of the total ATP requirements of a neuron!]
This transporter uses the energy of ATP to drive Na+ and K+ across the cell membrane, against their concentration gradients [a concentration gradient refers to the relative amount of a diffusible substance in two connected spaces. Again, equilibrium is the desired result, with equal concentrations in both spaces]: for every three Na+ that it moves OUT of the cell, it brings two K+ INTO the cell, leading to a net deficit of positive charges inside the neuron. This deficit is further amplified by passive movement of these ions along their concentration gradient across the cell membrane (as the cell membrane is only semi-permeable, there is always some diffusion across: it's just slow and somewhat inefficient), as specific K+ channels facilitate greater outward movement of K+ than there is inward movement of Na+. So, effectively, this is the neuron at rest:
Let's go through it again step-wise:
- There is a much higher concentration of Na+ outside the neuron than inside.
- There is a much higher concentration of K+ inside the neuron than outside.
- Left to their own devices, these ions would flow back and forth across the membrane until there were equal concentrations of both inside and outside the neuron.
- In addition, the electric charge ion gradient - the basis of the RMP - would be abolished.
- The semi-permeable membrane prevents this free movement, but there is some diffusion through specific channels in the membrane: these allow a much greater movement of K+ OUT of the neuron than Na+ INTO the neuron.
- The Na+/K+ ATPase pump actively transports Na+ and K+ AGAINST their concentration gradients; i.e., it brings K+ INTO the neuron where its concentration is already high, and takes Na+ OUT of the neuron, where its concentration was lower.
- Therefore, there are more positive charges leaving the neuron than entering (3Na+ for 2K+, AND, there is greater outward diffusion of K+ than inward diffusion of Na+), leading to a negative potential across the membrane that measures -70mV.
- The flow of ions across the membrane will change this, as you will see in the next section: for example, an influx of positive ions into the neuron will increase the membrane potential, making it less negative.
And now, the action potential...
This is all well and good, but where's the action? This resting state doesn't last for very long, and when the neuron receives input from its surrounding environment, there are changes in the membrane potential that can lead to the generation of our signal, or the AP.
The AP is said to obey the all or nothing law. This maintains that a certain stimulatory threshold has to be reached before the AP occurs, and once it's initiated, it cannot be stopped (see? biology IS exciting! Isn't this dramatic?!). The dendrites of the cell body or soma of the neuron are being constantly bombarded with information from other neurons, some stimulatory, and some inhibitory. This information is processed, and depending on its nature, triggers specific alterations in the membrane potential of the part of the axon closest to the soma (a.k.a., the axon hillock).
It all starts off as a local response, with subthreshold stimuli disturbing the RMP, without being sufficiently stimulatory to trigger an outright AP. Once the membrane potential reaches the magic number of -55mV, an AP will occur. The initial local response is due to some Na+ channels being opened, which allows influx of positive charge into the neuron. These voltage-gated Na+ channels are normally closed, but are opened when stimulated by the slight changes in membrane potential (known as depolarization) that are brought about by the subthreshold stimuli. Once threshold is reached, these channels start to open at an increased rate, leading to a massive influx of Na+, and the characteristic spike of the AP as the polarity of the membrane is reversed:
The AP is said to obey the all or nothing law. This maintains that a certain stimulatory threshold has to be reached before the AP occurs, and once it's initiated, it cannot be stopped (see? biology IS exciting! Isn't this dramatic?!). The dendrites of the cell body or soma of the neuron are being constantly bombarded with information from other neurons, some stimulatory, and some inhibitory. This information is processed, and depending on its nature, triggers specific alterations in the membrane potential of the part of the axon closest to the soma (a.k.a., the axon hillock).
It all starts off as a local response, with subthreshold stimuli disturbing the RMP, without being sufficiently stimulatory to trigger an outright AP. Once the membrane potential reaches the magic number of -55mV, an AP will occur. The initial local response is due to some Na+ channels being opened, which allows influx of positive charge into the neuron. These voltage-gated Na+ channels are normally closed, but are opened when stimulated by the slight changes in membrane potential (known as depolarization) that are brought about by the subthreshold stimuli. Once threshold is reached, these channels start to open at an increased rate, leading to a massive influx of Na+, and the characteristic spike of the AP as the polarity of the membrane is reversed:
These voltage-gated Na+ channels open ever more rapidly as the membrane potential increases, thereby resulting in dissipation of the Na+ concentration gradient. Eventually, however, the change in polarity causes closure of the Na+ channels, which is a nice example of feedback inhibition in biology! In addition, as more and more positive charges build up inside the neuron, Na+ entry gradually falls away (remember, the system strives to bring about a membrane potential of 0). Finally, voltage-gated K+ channels open more slowly and for a longer time period as the spike peaks. This causes substantial K+ efflux from the neuron, resulting in an overall deficit in positive charges and a transient 'undershoot' or after-hyperpolarization, where the membrane potential is briefly LOWER than the RMP. All of this occurs in MILLISECONDS...
What happens next?
Well, the signal is passed along the axon and onto the next neuron via the synaptic cleft. (This will be covered in more detail in Part II, so stay tuned!) This signal could eventually result in any number of outcomes: it could cause a muscle cell to contract, allowing you to pick up a pen and start writing a love letter. Or it could stimulate the release of a hormone into your bloodstream that will help regulate specific metabolic events. Or it could save you from a nasty burn, by causing you to withdraw your hand quickly from a hot stove. Our nervous system IS life and living; it really is that simple!