Health Psychology. Michael Murray
of 37.2 trillion cells plus or minus around 0.81 trillion (Bianconi et al., 2013) and there are hundreds of different cell types (Mescher, 2016). The cells in one body have identical DNA but carry out a coordinated myriad functions to enable the maintenance of a near-stable internal environment. Only by communicating with one another can the necessary high level of coordination be possible. The two primary organizations for cell–cell communication are the NS, using neurotransmitters such as acetylcholine, and the ES, which transports neuromodulators and hormones (e.g., cortisol) around the entire body. Most cell–cell communication occurs using intracellular enzymes, molecules that speed up chemical reactions (Michael et al., 2017). We outline here the basic structure and functions of the NS.
There are two main cell types in the NS, neurones and glial cells. Both cell types are absolutely necessary for neurological health. Glial cells provide support and nutrition, maintain local homeostasis, produce myelin and participate in signal transmission. The total number of glial cells roughly equals the number of neurons. Of particular importance are microglial cells, a type of glial cell accounting for 10–15% of all cells found within the brain. Microglial cells are highly plastic and act as macrophage (‘big eater’) cells, the main form of active immune defence in the central nervous system (CNS).
As both unique immune cells and unique brain cells that constantly change shape and have numerous different functions, microglial cells could stake a claim to being the ‘smart’ cells of the body. Microglia travel independently, unattached to any structure, circling a territory with extended arms seeking suboptimal functioning. This constant system of microglial surveillance protects the brain against any microbe invaders, demyelination, trauma and cancerous or defective cells (Lieff, 2013). When glial cells go wrong, all sorts of chaos can break loose, including brain inflammation and neurodegeneration, which can cause chronic pain (McMahon et al., 2005), Alzheimer’s disease (Paresce et al., 1996), Parkinson’s disease (Kim and Joh, 2006) and, according to some research, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (Morris and Maes, 2014). It can be seen already that intimate connections exist between the immune and nervous systems, and so far we have only mentioned the ‘foot soldiers’ of the NS and not the command structures.
Neurones provide the main ‘wiring’ of the NS; they are communication devices that connect with other neurones, tissues, organs and muscles. How the neuronal communication works can best be explained by looking at the structure of the neurone (Figure 2.2).
The brain contains around 86 billion neurones, 20% in the cerebral cortex and 80% in the cerebellum (Lent et al., 2012). Each neurone can connect with up to 1–10,000 other neurons so there may be as many as 860 trillion synaptic connections in total. Each neurone consists of a cell body or ‘soma’, dendrites and an axon. Dendrites are thin structures that arise from the cell body. They may be hundreds of micrometres in length and branch multiple times to produce a complex ‘dendritic tree’. An axon, or ‘nerve fibre’ when myelinated, arises from the soma at the axon hillock and travels for a distance which can be as far as one metre in humans (connecting the toe to the spinal column).
Figure 2.2 A schematic neurone and synapse
Source: Yurana’s portfolio, IMG ID:214981837, acquired via Shutterstock
Most excitatory synapses are formed between the axon of one neuron and a dendritic spine on another. When two neurons on either side of a synapse are active simultaneously, that synapse becomes stronger, a form of memory. The dendritic spine also becomes larger to accommodate the extra molecular machinery needed to support a stronger synapse.
Myelin is a fatty white substance that surrounds the axon of some neurones, providing electrical insulation. Multiple sclerosis (MS) occurs when an abnormal IS response produces chronic inflammation, which damages or destroys myelin.
Synapses and neurotransmission
One major form of communication in the NS uses neurotransmitters which are ‘squirted’ across an inter-cell channel called a ‘synapse’ or ‘synaptic cleft’. This feature is illustrated in Figure 2.3.
A wave of electrochemical excitation called an action potential travels along the membrane of the presynaptic cell, until it reaches the synapse. Channels that are permeable to calcium ions then open and calcium ions flow through the presynaptic membrane, increasing the calcium concentration in the interior. The increased calcium concentration activates a set of calcium-sensitive proteins attached to vesicles which contain a neurotransmitter. These proteins change shape, causing the membranes of some ‘docked’ vesicles to fuse with the membrane of the presynaptic cell, thereby opening the vesicles and dumping their neurotransmitter molecules into the synaptic cleft, the narrow space between the membranes of the pre- and postsynaptic cells.
To use an analogy, think of a couple of crazy kids having some fun in the school cafeteria when the teacher is nowhere to be seen. In a mêlée of hundreds of children all waiting for lunch, one kid picks up a bottle of ketchup and squirts it at the other kid’s face. If the ketchup squirt hits the target, and lands squarely in the other kid’s mouth, we have a successful ‘transmission’. If he misses, he’ll have to have another go, or another kid from the crowd will need to have a squirt to achieve a successful transmission. This is the kind of thing that goes on in neurotransmission across the synapse. The first kid with the ketchup bottle is the neurone, the bottle is the synaptic vesicle, the ketchup is the neurotransmitter, the first kid’s squeezy hand is the neurotransmitter transporter, and the second kid with ketchup all over his face is the receptor. The more ketchup on the face, the better the communication. Once the ketchup has done its job, it magically returns to the bottle. Job done! Unless, of course, that tomato ketchup is the ‘wrong’ kind of neurotransmitter and the receptor kid demands a certain flavour of ice-cream instead! These ‘ketchup kid fights’ are going on trillions of times every day in each and everyone of us.
Figure 2.3 The synapse, axon terminal, dendrites and associated processes
Source: Thomas Splettstoesser, Wikimedia Commons, CC 4.0 International license
There are at least 60 different kinds of ketchup – sorry, I mean neurotransmitter – to choose from. To be a neurotransmitter, a molecule must: (1) be red, sticky and taste like ketchup [no cancel that, just checking whether you’re concentrating], be produced inside a neurone, be found in the neurone’s terminal button, and be released into the synaptic gap upon the arrival of an action potential; (2) produce an effect on the postsynaptic neurone; (3) be deactivated rapidly, after it has transmitted its signal to this neurone; (4) have the same effect on the postsynaptic neurone when applied experimentally as it does when secreted by a presynaptic neurone. The best-known neurotransmitters are:
acetylcholine
serotonin
catecholamines, including epinephrine, norepinephrine and dopamine
excitatory amino acids, such as aspartate and glutamate (half of the synapses in the CNS are glutamatergic)
inhibitory amino acids, such as glycine and gamma-aminobutyric acid (GABA; one-quarter to one-third of the synapses in the CNS are GABAergic)
histamine
adenosine
adenosine triphosphate (ATP).
Peptides form another large family of neurotransmitters, with over 50 known members, including: substance P, beta endorphin, enkephalin, somatostatin, vasopressin, prolactin, angiotensin II, oxytocin, gastrin, cholecystokinin, thyrotropin, neuropeptide Y, insulin, glucagon, calcitonin, neurotensin and bradykinin. However, many peptides act more as neuromodulators than as neurotransmitters. Neuromodulators