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Next Lesson - Arterial Supply to the Brain
Abstract
- The CNS is made up of neurones and their supporting cells, called glia. Astrocytes are the most abundant glial cell, provide support and nutrition for neurones, and make up part of the blood brain barrier. Oligodendrocytes create the myelin sheath of neurones in the CNS. Microglia are the immune cells of the CNS.
- There are three main categories of neurotransmitter in the brain: amino acids (like glutamate, GABA, and glycine), biogenic amines (like noradrenaline, dopamine, serotonin, and acetylcholine) and peptides (like substance P, somatostatin, and cholecystokinin). They all have different, specific functions.
Core
The central nervous system is made up of neurones and their supporting cells, called glia.
Neurones receive information and transmit this to other neurones. Glial cells support, nourish and insulate neurones, and remove ‘waste’ from the neurones.
Astrocytes are the most abundant type of glial cells. They have a number of functions:
- Structural support of neurones
- Help provide nutrition for neurones through the glucose-lactate shuttle as neurones cannot store their own glycogen.
- Control concentrations of neurotransmitters such as glutamate through reuptake to prevent toxicity.
- Maintain the ionic environment through uptake and buffering of potassium.
- Help to form the blood brain barrier.
Oligodendrocytes are responsible for myelination of axons in the central nervous system. These oligodendrocytes are the CNS equivalent of Schwann cells, which are responsible for myelination in the peripheral nervous system.
Microglia are the immune cells of the central nervous system and are the brain’s main defence system. They are activated by foreign material in the brain and undergo phagocytosis to remove this. They also act as antigen presenting cells.
It is important that the central nervous system has its own immune system because the body’s normal pro-inflammatory response would be dangerous within the confined bony structure of the skull. The CNS therefore takes steps to inhibit the normal immune response.
The blood brain barrier (BBB) is a highly selective semi-permeable membrane of endothelial cells that controls the environment of the neurones by acting selectively with solute transport into the CNS. Substances such as glucose, amino acids and potassium are transported across the BBB so the concentration can be tightly controlled.
There are over 30 neurotransmitters in the CNS. They can be split broadly into three chemical classes:
Examples: glutamate, GABA, glycine.
There are two main types of amino acid neurotransmitters: excitatory and inhibitory.
The main excitatory amino acid is glutamate, which makes up 70% of all CNS synapses.
The inhibitory amino acids are GABA and glycine.
Glutamate receptors can be classified into ionotropic or metabotropic receptors. This means that they either affect ion channels (like Na+, K+, or Ca2+), or they affect the metabolism of other chemicals (such as cyclic AMP).
Glutamate receptors of types NMDA and AMPA team up to cause the fast excitatory response of a synapse, resulting in an action potential.
AMPA receptors mediate the initial fast depolarisation.
NMDA receptors are permeable to Ca2+ and become active once the cell has been depolarised, allowing the influx of calcium ions to be delayed until after depolarisation. This delay results in long term potentiation of the synapse, a process that strengthens the synapses and leads to a long-lasting increase in signal transmission over this synapse. In simple terms, the activation of NMDA receptors allows the synapse to depolarise more easily the next time an impulse occurs.
This concept is called plasticity.
GABA is the main inhibitory neurotransmitter in the brain, and glycine is the main inhibitory neurotransmitter in the brainstem and spinal cord.
GABA and glycine receptors work the same way; they work by opening Cl- channels, causing hyperpolarisation of the neurone. This means that the membrane potential of the post-synaptic membrane is below the resting potential, making it harder for any action potentials to occur.
Medications such as barbiturates and benzodiazepines make use of the GABA receptors in the brain as both of these classes of medication increase the effects of GABA receptors in the brain. This gives them an anti-anxiety and sedative effect that can be very addictive.
Examples: acetylcholine, noradrenaline, dopamine, serotonin, histamine.
Biogenic amines act as neuromodulators in the CNS, meaning their neurotransmitter action is used with a specific pathway.
Acetylcholine (ACh) has two main functions within the CNS.
The first is widespread within the brain itself; it acts mainly as an excitatory neurotransmitter in the brain at both nicotinic and muscarinic receptors (nicotinic receptors are ion channel receptors, and muscarinic receptors act by phosphorylating intracellular messengers).
The second is within a neuromuscular junction; acetylcholine is the neurotransmitter used in the parasympathetic nervous system.
Acetylcholine is therefore involved in many functions: arousal, motor control, learning and memory, as well as the functions of the parasympathetic nervous system. One key example demonstrating the action of acetylcholine in memory is the use of cholinesterase inhibitors (drugs that inhibit the breakdown of acetylcholine and therefore increase the concentration of acetylcholine in the synapses) in the treatment of Alzheimer’s Disease.
Dopaminergic pathways in the brain are involved in two main ways: one pathway contributes to motor control, and the other to mood, arousal and reward. The dysfunction of these pathways causes different pathologies.
Dysfunction of the motor control pathway results in Parkinson’s Disease – a condition caused by the loss of dopaminergic neurones in certain pathways in the brain. It can be treated through giving exogenous (external) dopamine through a medication called LDOPA, which is converted to dopamine within the body.
Dysfunction of the pathways involved in mood, arousal and reward has been implicated in the disease schizophrenia. It is thought that some of the symptoms of schizophrenia result from too much dopamine being present in the pathways in the brain, and so some medications used in the treatment of schizophrenia act to reduce the effects of this excess dopamine (some antipsychotics are dopamine receptor antagonists).
Noradrenaline acts as a neurotransmitter within the central nervous system and the autonomic nervous system. Most noradrenaline in the brain is produced in a group of neurones called the locus coeruleus.
Noradrenaline has a role in wakefulness and mood. This is shown through the actions of medications: amphetamines act to increase noradrenaline, and therefore increase wakefulness and mood, and some antidepressants increase noradrenaline to combat the drowsy, low mood state that can occur in depression.
Serotonin has similar functions to noradrenaline in the brain in that it contributes to sleep/wakefulness and mood. Medications such as SSRIs (selective serotonin reuptake inhibitors) act to increase the amount of serotonin in the synapses, and are used as a treatment for depression and some anxiety disorders.
Examples: enkephalins, substance P, somatostatin, cholecystokinin.
There is a third class of neurotransmitters in the CNS and in the wider body. Their CNS functions are beyond the scope of this article, but their other relevant functions (such as the effects of somatostatin and cholecystokinin in the gastrointestinal tract) should be learnt.
Edited by: Dr. Marcus Judge
Reviewed by: Adrian Judge
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