Editor: This article is the first of a two-part series. Check out Part Two here.
Neuroscience is generally defined as the study of the nervous system, but this study usually involves a large number of fields such as biophysics, biochemistry, and anatomical biology.
To further appreciate the complexities of the nervous system and how this links to its role in everyday processes such as memory, coordination, and decision-making, we must first understand how the nervous system operates and what mechanisms it has in place to aid in its function.
The nervous system
The nervous system helps us respond to changes in the environment (called stimuli) by sending out electrochemical signals throughout the body, thereby resulting in the production of necessary actions.
It can be split into two parts:
The central nervous system (CNS) comprising of the brain and spinal cord
The peripheral nervous system (PNS), which is made up of nerves present in the body. This includes the somatic, autonomic, and enteric nervous systems.
The central nervous system
As mentioned above, the CNS comprises the brain and the spinal cord. Generally speaking, the brain coordinates the body’s responses to stimuli as well as its functions. The spinal cord, on the other hand, connects the CNS to the PNS, allowing the brain to direct and coordinate responses across the body. The CNS obtains sensory information on changes in the environment from nerves in the PNS, and then processes this information. After processing, it sends back ‘instructions’ into the PNS on how to respond to any changes in the environment based on what information it has received.
The peripheral nervous system
The PNS can be split into two parts: the somatic nervous system, and the autonomic nervous system.The somatic nervous system is responsible for movement, and is mostly made up of motor (efferent) and sensory (afferent) neurons. Sensory neurons detect changes in the environment and inform the CNS of these changes; motor neurons control muscle movement with relation to information they have received from the CNS. Meanwhile, the autonomic nervous system can be split into two further parts: the sympathetic and parasympathetic system. The parasympathetic system helps regulate and maintain the body’s regular resting state, whereas the sympathetic system regulates the body’s fight or flight response, allowing for quick responses during stressful or dangerous situations.
Figure 1: An overview of the functions of the Central Nervous System (CNS) and Peripheral Nervous System (PNS). Adapted from Cornell, B. 2016. Nervous system [ONLINE] at http://ib.bioninja.com.au [Accessed 1st October 2020]
Introducing neurons
Neurons are the building blocks of the nervous system. The mammalian brain contains around 100 million to 100 billion neurons that constantly send and receive electrochemical signals rapidly and precisely. These neurons are responsible for coordinating various functions and responses in your body - as innocuous as remembering what you had for lunch yesterday, or as complex as trying to comprehend PhD-level research.
In order to carry out their function, neurons have a specialised structure that helps them adapt to their function. Although neurons may differ slightly in aspects of their structure, most contain three main features: a cell body, axon, and dendrites.
Figure 2: The anatomy of a neuron, with all cell structures labeled. Neurons have specialised features such as dendrites which are extensions of the cell body that receive information from other neurons. The axon is another extension of the cell body, and gives rise to synaptic knobs which contain junctions called synapses. Both synapses and axons are involved in the transmission of electrochemical signals. The myelin sheath is an insulating layer that increases the speed of signal transmission in neurons. The node of Ranvier is an uninsulated part of the axon that allows for the diffusion of ions in and out of the axon. Adapted from Dhp1080 from Creative Commons.
The cell body of the neuron contains a nucleus and a cytoplasm, as well as mitochondria (which produces energy for the cell to aid in its processes). Additionally, the cell body may also contain neurotransmitters, which are chemical messengers that help send signals to other neurons or cells around the body.
The neuron also contains an axon, which is an extension of the cell body. This extension in length allows neurons to transmit electrochemical signals over larger distances. At the end of the axon, smaller branches that contain synaptic knobs form, before ending at terminal branches. Following that, the synaptic knob is where synapses are found- this is where communication between neurons occurs.
Axons on a neuron may be surrounded by myelin, which is made up of protein and lipids. The surrounding layer around the axon is called a myelin sheath, and acts as an insulating layer that allows electrochemical signals to be transmitted efficiently along nerve cells. Nodes of Ranviers are unmyelinated parts of the axon that allow for ions to diffuse in and out as their diffusion is not barred by the non-polar myelin sheath.
Lastly, neurons contain dendrites, which are essentially extensions of the cell body that receive information from other neurons.
Glial cells and myelin sheaths
Besides the three main structural features of a neuron, other cells play a fundamental role in the nervous system. These cells are called glial cells, and there are various types such as astrocytes, oligodendrocytes, microglia, and many more. Although these cells are found in both the CNS and PNS, each system contains different types of glial cells that perform different functions that support the nervous system.
For example, glial cells such as Schwann cells and oligodendrocytes are responsible for the myelination of axons. Studies have shown that without a myelin sheath, the rate of transmission of electrochemical signals slows down from 150 m/s to 0.5-10m/s. This may have adverse effects on the body- for example, the disease multiple sclerosis (MS) may occur when immune cells attack myelin sheaths and glial cells.
Organisms that do not have myelinated axons - such as the giant squid - may have giant axons in their nervous system instead. These are axons with a large diameter, which allow for a more rapid transmission of electrochemical signals due to the decreased resistance. This is an adaptive strategy that allows them to make faster responses to stimuli during fight or flight situations.
Electrochemical signals
Neurons send and receive electrochemical signals. These signals have both an ‘electric’ and ‘chemical’ component to them that can be broken down in the following way.
The ‘electric’ part involves the transmission of electrical impulses called action potentials, which are generated when a stimulus is present. Once the action potential travels down the axon to the synaptic knob, it triggers the release of neurotransmitters, hence the ‘chemical’ part of this electrochemical signal. The release of neurotransmitters passes on this signal to the other neuron, and the process is repeated until the signal reaches the intended recipient. This is called synaptic transmission.
Membrane potential - generation and maintenance
Membrane potential
Before diving into how action potentials are generated, we ought to define membrane potential, as well as understand how it is generated and maintained.
The plasma membrane of a cell is made up of phospholipids, and also contains proteins that control the exit and entry of specific ions into the cell such as ion channels. Ion movement must be controlled as many amino acids and proteins are charged. Disruption in ion concentrations can affect these proteins as ions of opposite charges may bind to charged amino acids and proteins, changing their structure and function as a result. The alteration of structure and function in ion channels may lead to channelopathies, which are several diseases that arise as a result of ion channel malfunction.
Figure 3: The structure of the plasma membrane. The membrane is made up of phospholipids, as well as several types of membrane proteins that span the outside or inside of the membrane. Adapted from Cornell, B. 2016. Fluid-mosaic model [ONLINE] at http://ib.bioninja.com.au [Accessed 1st October 2020]
Therefore, a voltage difference is generated as a result of the control of ionic movement across the plasma membrane, and is referred to as the membrane potential. The membrane potential of cells is normally maintained at around 30-70 millivolts (mV), and is referred to as the ‘resting potential’. However, this may differ from cell to cell. The resting potential in neurons is -70mV.
Although this concept seems straightforward, there are two requirements that are needed for the generation and maintenance of a membrane potential.
1. Electrochemical gradient
At least one charge must be more concentrated on one side of the membrane than the other. This generates an ion concentration gradient, similarly observed in diffusion.
2. Ion flow
Ions must be able to flow across the membrane.
Using these two criteria and what we already know from diffusion, we can infer that the ion will diffuse across the membrane from a higher concentration gradient to a lower concentration gradient. When this happens, a current is generated.
However, the voltage difference that generates the previously mentioned membrane potential is generated from this current flow. The Ohm’s law in physics explains how this voltage difference is generated from current:
Voltage = current x resistance (V = IR)
Ions do not directly flow across the membrane, instead they move across it via ion channels. Therefore, the ion channels represent resistance in this case, and the ions that are moving in and out of the channel represent the current. If we use this analogy and substitute it into the equation above, we can conclude that voltage is generated.
Generation and maintenance of the membrane potential
Our cells generate membrane potentials by controlling Na+ and K+ concentrations inside and outside the membrane.
There are more potassium ions (K+) inside the cell compared to the outside. Normally, this would mean that there is a lower water potential inside the cell compared to the outside, therefore water should rush into the cell as a result, causing it to swell. However, our bodies avoid this by raising the concentrations of sodium ions (Na+) outside of the cell, lowering the water potential outside of the cell and maintaining osmotic equilibrium.
This generation of membrane potential also results in an equal number of negative and positive charges across the membrane, so it is electrically neutral.
However, this concentration needs to be maintained. There are two mechanisms by which the membrane potential is maintained:
Na+/K+ pumps, which pump Na+ and K+ ions in and out of the channel
Exchangers, which ‘take’ the energy used when an ion is transported down its concentration gradient to transport another ion against its concentration gradient
Na+/K+ pumps
Na+/K+ pumps are proteins that use ATP as an energy source to pump Na+ and K+ ions out and in respectively. In fact, for every 3 Na+ ions pumped out, 2 K+ sodium ions are pumped in. The pump requires energy to function as it is pumping ions against their concentration gradient, and obtains this energy by hydrolysing ATP.
Figure 4: A diagram outlining the structure and function of the Na+/K+ pump. The grey line is the plasma membrane, and the grey area represents the inner membrane space. For every 3 Na+ pumped out, 2 K+ ions are pumped in. This process requires energy as it moves ions against their concentration gradient, and this energy is obtained via the hydrolysis of ATP as shown. Adapted from Pivovarov, Calahorrow and Walker, 2019.
Exchangers
Exchangers are proteins that ‘take’ the energy released by the movement of Na+ ions down their concentration gradient and use it to move another ion against their concentration gradient.
A common example of this is the Na+/Ca2+ (calcium ion) exchanger, where the energy used to transport Na+ down its concentration gradient is dissipated and used to transport Ca2+ ions against their gradient instead. This mechanism is used to control heart and muscle contraction, therefore maintenance of these ion concentrations are crucial.
Figure 5: A diagram outlining the structure and function of the Na+/Ca2+ pump. The grey line is the plasma membrane, and the grey shading represents the inner membrane space. For every Ca2+ transported out, 3Na+ are transported in. Adapted from Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. (2003). Retrieved October 7 2020.
Action potentials and depolarisation - putting the ‘electro’ in electrochemical signal
Action potentials are generated in a variety of excitable cells- cells whose membranes are in a polarised state- such as nerve and muscle cells.
In a neuron, the resting potential is maintained at -70mV. When a stimulus reaches the neuron, this causes sodium channels to open, which are normally closed at resting potential. After this occurs, Na+ ions diffuse into the axon, raising the membrane potential above -70mV. This is called depolarisation.
When the potential rises to -55mV, this causes other voltage-gated sodium channels to open. These can only open when a certain voltage (-55mV) is reached. This voltage is called the ‘threshold potential’. When this threshold potential is achieved, an action potential is generated. If the voltage generated by initial depolarisation is less than -55mV, action potential does not occur, regardless of what the stimulus is. This is called the ‘all-or-nothing’ rule- either an action potential occurs, or it doesn’t.
The opening of these channels cause more Na+ ions to flood into the axon, leading to complete depolarisation. This raises the membrane potential to +55mV. After this occurs, Na+ channels shut, and K+ channels open, allowing K+ ions to diffuse out. This leads to a decrease in membrane potential that dips below -70mV. This is called hyperpolarisation.
Gradually, the membrane potential slowly goes back to resting potential as repolarization occurs. Crazily enough, this whole process occurs over the course of a few milliseconds!
Moreover, this whole process occurs in one direction down the axon, as polarised regions cannot be re-polarised until after a certain amount of time. This allows for the stimulus to be spread further down the axon until it reaches the synaptic knob. Once it reaches the synaptic knob, this leads to the release of neurotransmitters, which is the ‘chemical’ part of the electrochemical signal that we will explore in the second part of this topic.
Figure 6: A graph showing the changes in voltage over the duration of an action potential. Figure adapted from original by Chris73; updated by Diberri on Creative Commons.
Neurobiology in action
The core functions of the nervous system include coordinating responses such as movement based on information received from the environment, and maintaining higher functions such as memory, critical thinking, and our emotions. All of these are functions that we require and execute in our daily life, and learning about how electrochemical signals are received and transmitted is just the tip of the iceberg when it comes to studying neurobiology as a topic.
Understanding the functions of the nervous system and its components is crucial in determining the effect of chronic illnesses such as multiple sclerosis on the body, which arises due to a breakdown in nervous system functions. This is important in determining which medical treatments can be developed to aid people with this condition, as well as further studies in predicting how this disease may occur.
Zoe Cheah, BSc Biological Sciences