The different neurons in our brains, and in particular the interaction between them, are responsible for human behaviour. They do this by sending and receiving neurotransmitters. Knowledge of associated processes is very important to have a good understanding of the effect of psycho pharmaceuticals.

This chapter describes the functioning and interaction of neurons to get a better picture of how the brain responds to the environment and adapts to it.

What does the structure of neurons look like?

The different neurons in our brains do not all look the same. The function and location of the neuron affects the size, shape and other properties of the neuron. The three most important neuronal groups are sensory neurons, motor neurons and interneurons. The sensory neurons pick up signals, the brain interprets these signals and the motor neurons then respond to this. In the central nervous system you find the interneurons which enables the transition between the other two groups of neurons.

The cell body

The cell body is also called soma and is the largest part of the neuron. Here the metabolism of the cell takes place and you can find the nucleus with DNA.

Dendrites

Dendrites receive signals from surrounding neurons. The more dendrites a neuron has, the more information this neuron can receive. The location of the neuron affects the number of dendrites, for example, interneurons have more dendrites than neurons in the spinal cord.

Axons

The signal from the neuron is passed through the axon, which is an extension of the cell body and can have a length of a few millimetres to tens of centimetres. The axon hillock is the place where both the axon and the electrical signal start. Some axons have a myelin layer, especially the peripheral axons. The myelin is a glial cell that isolates the axon and enables an accelerated transportation.

Terminal button

The end of the axon is called the terminal button. Here, neurotransmitters are stored, released and in some cases reuptake takes place. A particular protein is very important for this reuptake, which will get more attention later in this chapter, as many psychotropic drugs work on this protein.

Neural transfer

The neural transfer is the process by which the signal from the terminal button is transported to the dendrite of the next neuron (in the central nervous system). Signals are transmitted through nerves in the peripheral nervous system.

Electrical activity in the neuron

The lipid bilayer is a double layer of lipids that form the membrane of the neuron. This membrane enables that the neuron can have its own internal environment. In the membrane there are proteins which enable that glucose and ions can enter the cell and carry waste products out of the cell. By transporting the ions, the electric potential of the neuron changes. The important ions are An - , Cl - , Na + and K + . The sodium and chloride ions only enter the cell when they are permitted, through the ion channels (proteins). They become active due to changes in the membrane.

Resting potential

The charged ions have to deal with two forces: diffusion and electro stasis. When there is an equilibrium between these forces, a state of rest takes place. The electrical potential of the neuron during rest is determined by the distribution of the positive and negative ions. Due to the cellular properties, cells are negatively charged during the resting potential, while a positive charge exists outside the cell. There is often a load of -70 mV in the cell. This resting potential helps the cell store energy. This energy can be used when the cell is activated.

Graded potentials

As soon as a neuron receives a signal from another neuron, the resting potential (-70mV) is disturbed. This disturbance is called a graded potential. In case of rapidly successive or simultaneous graded potentials, the threshold value is reached and the neuron depolarizes, creating an action potential.

Action potentials

The threshold value for depolarization and thus the creation of an action potential is approximately  -55mV. During a depolarization a load shift occurs from -70 to +30mV. This is because the sodium ions (Na+) are left through the cell membrane. In addition, some negative ions leave the cell. After this, the resting potential restores, resulting in a short hyper polarization in the membrane. The action potential alone lasts only 1 millisecond.

Once the action potential reaches the terminal button, neurotransmitters will be released allowing the receiving neurons to transmit the process. The degree of intensity of the action potential is always the same: there is an all-or-none principle. A neuron therefore always has the same intensity when transmitting the signal. There are other factors that can contribute to the strength of the signal: the amount of neurons that are active and the amount of the action potentials.

The properties of the axon determine the speed at which an action potential reaches the next neuron. Both the resistance (smaller in the case of larger axons) and the myelin sheathing result in greater speed. The myelin in the central nervous system consists of oligodendrocytes. In the peripheral nervous system Schwann cells produce the myelin. Between each glial cell the axon has a small opening called nodes of Ranvier. Here sodium can facilitate depolarisation. The action potential does not slide along the axon, but goes from node to node in jumps. This is called saltatory conduction and makes the process run faster.

The above knowledge tells us why diseases where myelin disappears (such as MS) have such far-reaching consequences: the nerve impulses move much more slowly.

Other glial cells than previously mentioned, the astrocytes, also play an important role in the nervous system. They help with the migration of developing neurons and with the formation of connections between different neurons.

The communication between neurons mainly consists of the release of neurotransmitters. Less common is the electrical synapse, where an electrical signal from neuron to neuron is transmitted. The process of the electrical synapse will not be discussed further.

How does synaptic transfer proceed?

Release of neurotransmitter

When an action potential reaches the terminal button, calcium can penetrate here too. This allows that the neurotransmitters in the presynaptic membrane can be released. The amount of calcium determines the amount of neurotransmitters that will be released. This is controlled by proteins, which can affect certain drugs.

Receptors

The postsynaptic membrane of the receiving neuron captures the neurotransmitter in receptors. The molecular design of the receptor determines which neurotransmitters can and cannot bind. Drugs work on this fact: they can mimic the action of neurotransmitters and thereby bind to a receptor, or they can block receptors instead.

An ionotropic receptor directly controls the ion channel. A metabotropic receptor is bound to ion channels that it does not control itself. This enables that ionotropic receptors are much faster. However, the metabotropic receptors need more time.

Re-uptake of neurotransmitter

Some neurotransmitters are broken down by enzymes once the signal has been passed to the next neuron. These enzymes are made by the same neuron that makes the neurotransmitters. The broken down substances are then taken up again by the terminal button where they will be recycled. Sometimes neurotransmitters are recycled as a whole. The process of reuptake is controlled by transporter proteins. More of these proteins gives a quicker reuptake process. Different drugs can influence this, these drugs can facilitate that the breakdown process or reuptake will be blocked.

Excitatory and inhibiting synapses

The permeability of the postsynaptic membrane can be adjusted by allowing some cells to enter the cell. The ion channels allow both positive and negative ions to enter the cell. Positive ions facilitate that the membrane becomes depolarized (becomes more positive). This is what happens with exciting neurotransmitters. They send excitatory postsynaptic potentials (EPSPs). When negative ions are allowed to enter the cell, the action potential is inhibited (the cell becomes more negative). This happens with inhibitory neurotransmitters, which send inhibitory postsynaptic potentials (IPSPs). Both EPSP and IPSP can take place simultaneously. To achieve an action potential, there must be more EPSPs than IPSPs, otherwise the threshold value will not be reached.

There are neurons that are specifically excitatory or inhibitory. Other neurotransmitters are sometimes excitatory and sometimes inhibitory. In the last case, the effect will be determined by proteins in the postsynaptic receptor.

Autoreceptors

Autoreceptors are receptors located on the presynaptic neuron. They regulate the activity of this neuron. The amount of neurotransmitters that is released can thus be controlled. The autoreceptor does this by regulating the internal cell process via secondary messenger systems.

Heteroreceptors

Heteroreceptors receive neurotransmitters from other neurons. Like autoreceptors, these receptors are metabotropic, so the effects are obtained by a secondary messenger system. These receptors can both enhance or inhibit the process within the cell.

What is the function of neurotransmitters?

About fifty different neurotransmitters are known. Other substances in the nervous system are called neuromodulators. They modulate the effects of neurotransmitters. A substance is called a neurotransmitter when:

• The substance is synthesized and stored in the presynaptic neuron;
• The substance is released into the synapse after activation of the neuron;
• The substance a postsynaptic effect causes after interaction with the receptor;
• There is a breakdown or reuptake mechanism.

Acetylcholine

Acetylcholine was the first neurotransmitter that was discovered (1921). A disease in which acetylcholine plays an important role is Alzheimer's disease. The amount of acetylcholine in the basal forebrain decreases. To treat Alzheimer's symptoms, medication with acetylcholine can be administered.

There are two types of acetylcholine receptors: muscarinic (metabotropic) and nicotinic (ionotropic) receptors. The first type of receptor is important in cognitive and motor functions and for reward. The second type of receptor can be found on all muscle cells. When they bind with acetylcholine, they control the calcium channels which leads to muscle contractions.

Norepinephrine

Norepinephrine is spread by both the central and the peripheral nervous system. The neurotransmitter play a role in the maintenance of cortical excitation by using the reticular activating system (RAS) . This system affects attention, emotion and food. Organ regulation is also an important part. There are different types of receptors to which norepinephrine can bind and these receptors all have different functions. All receptors for norepinephrine are metabotropic, so they activate secondary messenger systems. There are two subtypes, α and β which in turn consist of two types. The α 1 , β 1 and β 2 receptors are excitatory and the α 2 receptor is inhibitory.

Dopamine

Dopamine can be found in the nigrostratial pathway (substantia nigra, which is important for voluntary movement and the initiation of movement), the pathway in the ventral tegmental areas of the punch (mesolimbic system) and the pathway that projects on the frontal cortex (mesocortical system or the reward system). When dopamine in the nigrostratial pathway decreases, Parkinson's disease may develop. Drugs mainly affect the reward system. The three pathways mentioned also seem to play a role in schizophrenia.
The two main receptors in dopamine (D 1 and D 2) activate the secondary messenger system, but have opposite effects. D 1 activates the second messenger AMP and D 2 inhibits it.

Serotonin

Serotonin belongs to the monoamines and diffuses in the brain and spinal cord. Serotonin affects the sleep-wake pattern, mood, aggressive behaviour and appetite. This neurotransmitter, like the previously mentioned neurotransmitters, develops in the brainstem. There are many different subtypes of serotonin, some of them possess autoreceptors and some have metabotropic receptors. The many different receptors have their own functions and can be found in different areas in the brain.

Glutamate

Glutamate is an amino acid that is obtained from glutamine. The substance plays an important role in long-term potentiation , this is the process of changing the neuronal functioning to benefit learning and memory. Glutamate does not appear in the brainstem. The brain areas with projections on the cerebral cortex, hippocampus and the cerebellum contain the most glutamate. The receptors for glutamate can be both ionotropic and metabotropic. You have the receptors AMPA, kainate and NMDA, but the main receptor is NMDA. This receptor can be both ionotropic and metabotropic and plays an important role in long-term potentiation. It turns out that long-term potentation is one of the long-term synaptic changes that plays a role in learning. Drugs that disrupt NMDA can therefore hinder learning.

GABA

The largest inhibitory neurotransmitter is GABA (Gamma-Amino-Butyric Acid). This neurotransmitter is located in both the brain and the spinal cord. Neural inhibition is important for regulating and controlling all physiological and behavioural functions. Different drugs have an effect on the functioning of GABA, resulting in changes in behaviour and mood. The neurons secreting GABA are located in different brain areas such as the basal ganglia and the cerebellum. Most of the GABA neurons are interneurons. The receptors can be ionotropic (GABA A) or metabotropic (GABA B). Most drugs have an effect on the GABA A that functions both as a postsynaptic and as an autoreceptor (regulation of the synthesis and release of GABA).

Endorphins

Endorphins consist of peptide neurotransmitters that chemically resemble opiates. These neurotransmitters are located in the brain and spinal cord. Different behavioural and psychological processes are influenced by this neurotransmitter group including the feeling of being surprised, a feeling of euphoria, discouraging the influence of stress and the regulation of the intake of food and drink (metabolic processes). Three types of receptors for endorphins are known and all are metabotropic. These three are μ (mu), κ (kappa) and δ (delta).   

Substance P

Substance P belongs to the peptide neurotransmitters. This substance mainly receives messages from the nociceptors and plays a role in pain.

What is important in the organization and structure of the nervous system and the brain?

The nervous system consists of the central (brain and spinal cord) and peripheral (muscles, glands, organs and skin) nervous system. These two nervous systems have to work together. Drugs used for psychological disorders often have an effect on both systems. During treatment, the focus is on effects on the central nervous system, while there are often many peripheral side effects.

The central nervous system

The cerebral cortex is the outer part of the brain, including many other structures. The left and right half of the cortex are separated by the longitudinal sulcus. The two sides are also called hemispheres.

Cerebral cortex

As mentioned above, the thin outer layer of the brain is the cerebral cortex and is also called the neocortex. There are many deep grooves in the cortex these are called fissures or a sulci. A protrusion (brainwinding) is called a gyrus. The cortex can be divided into four lobes: the frontal lobe, temporal lobe, parietal lobe and the occipital lobe. These lobes are subdivided into several functional areas.

Spinal cord

Messages to and from the brain are spread through the spinal cord. In addition, the spinal cord regulates reflexes in which the brain is not involved since reflexes can be seen as simple, automatic responses.

Medulla

The medulla is the lowest part of the brain and is located just above the spinal cord. The medulla is important in the control of the vital functions (for example breathing, heartbeat, blood pressure, consciousness, reflexes), awareness and regulation of reflexive functions (such as sneezing and coughing).

Punch

The punch is located (dorsally) above the medulla. This structure is important in refining the motor signals and processing sensory (especially visual) information.

Cerebellum

The main function of the cerebellum is to coordinate and regulate motor movement. The cerebellum refines movements (for example the timing of movement). In timed movements, the process of learning is very important. When this structure gets damaged, movements become awkward and uncoordinated. In addition, speech can deteriorate.

Reticulate formation

The reticular formation consists of neural structures from the medulla to the thalamus. These structures are important for awareness and controlling excitement and alertness. This series of structures is called the reticular activating system (RAS). It seems that this system produces too little excitement in people with ADHD.

The reticular formation also appears to be important in the sleep pattern. Little is known about this, however. We do know that people with damage to these structures are extremely drowsy and they can even get into a coma for a long time.

What is the function of the limbic system?

The limbic system is very important for emotion and motivation. In addition, the associated structures also play a role in learning and memory. The limbic system includes the amygdala, the hippocampus, the nucleus accumbens and the hypothalamus (partly). Damage or stimulation of areas in this system can give raise to extreme reactions to a situation or a reduced emotional response.

Amygdala

The amygdala is located in the inferior temporal lobe. The structure is important in the expression of anger, aggression, learning and fear of motivated behaviour. The amygdala is also important in social cognition and decision making. Damage in this area ensures that a memory no longer evokes an emotional state.

Nucleus accumbens

The nucleus accumbens is part of the mesolimbic-cortical system, which is an important pathway for dopamine.

Hippocampus

The hippocampus is particularly important in forming new memories. This structure seems to be sensitive to stress. People who experience a lot of stress often have a smaller hippocampus. People with schizophrenia or post-traumatic stress disorder also have a reduced hippocampus. The stress hormone cortisol can cause both atrophy (tissue decline due to cell death) and the growth of new cells. Both can lead to a decreased memory.

Hypothalamus

'The hypothalamus is located beneath the thalamus and above the optic chiasm. This structure plays a role in physiological functions and the motivation of behaviour. In addition, the hypothalamus is important for the neuro-endocrine system. This structure facilitates the production of hormones that activate the pineal gland. The pineal gland produces different hormones (growth hormone, male hormones, female hormones, etc.).

Thalamus

The thalamus consists of two oval-like lobes that lie next to each other, each in a different brain. All sensory information (except smell) is passed through the thalamus.

What is the function of the basal ganglia?

The basal ganglia includes the caudate nucleus, putamen and the substantia nigra. These brain structures receive information from both the cortex and the thalamus. This information is used by the basal ganglia for the coordination of motor movement. People with Parkinson's disease suffer from a reduced amount of dopamine in the substantia nigra. This reduces the activity in the entire basal ganglia. Another movement disorder, tardive dyskinesia seems to arise when people use antipsychotics for a longer period of time. These medications block dopamine receptors, by which they make them hypersensitive. This, in turn, causes excessive movement.