Last time we looked at the basics of nerve cell communication. We touched on the electrochemical process; the combination of electrical pulses through an axon and chemical signalling across synapses, that constitute the activity of a neuron. In this blog we are going to take a closer look at the chemical part of the process, and give a little more detailed discussion on the various neurotransmitters involved.
Let me give a quick re-cap from last time in regards to the activity at the synapse (refer to diagram from part 1): When an action potential (the electrical pulse) travels down an axon to the presynaptic axon terminal it causes a change in the membrane of the cell, allowing calcium into the terminal. This influx of calcium causes the synaptic vesicles to fuse to the membrane of the terminal at special places where neurotransmitters are then released, from the vesicles, into the synaptic cleft. Some of the neurotransmitters are then taken up by receptors on the postsynaptic terminal (of the dendrite of another neuron), which in turn triggers certain reactions within the receiving cell, causing either inhibition or excitation to fire.
Neurotransmitters are the chemical molecules that are released from presynaptic terminals and are received by postsynaptic receptor sites. For this ‘basic neural science for psychotherapists’ survey, I am simply going to generate a helpful list that I will make reference to later on.
These are the classes of neurotransmitters:
A) Amino Acid Neurotransmitters (these are the major neurotransmitters)
1) Glutamate (an excitatory neurotransmitter)
2) Gamma-aminobutyric acid (GABA) (an inhibitory neurotransmitter)
B) Biogenic Amines (monoamines) (these are more localised in distribution than the amino acids and are know to also be released from non-synaptic sites)
1) Catecholamines (cause physiological changes to prepare the body for physical activity such as the “fight-or-flight” response)
Dopamine (has many functions – most dopaminergic neruons are in the midbrain and hypothalamus)
Norepinephrine (acts as a hormone and a neurotransmitter – it increases heart rate, acts as a stress hormone affecting the amygdala)
5-HT (Serotonin) (regulation of mood, appetite, sleep, also involved in memory and learning – a major antidepressant)
C) Acetylcholine (only used by a few cell groups and is the major neurotransmitter in autonomic ganglia)
D) Peptides (large and diverse group of transmitters and some act as hormones, including enkephalines and endorphins)
E) Others including histamine and epinephrine, plus about 60+ others that have been identified.
This is going to be our basic reference list of neurotransmitters. As I continue on in this series I will make reference back to this list. When we look at more specific cases of neural activity, and we talk about monoamine receptors or a GABA receptor, you will be able to picture where the appropriate neurotransmitters fit in the larger scheme of neural chemicals.
Starting and Stopping Neurotransmitter Action
A neurotransmitter released into the synaptic cleft is taken up only by postsynaptic receptor sites designed to receive that particular chemical. The neurotransmitter can be thought of, in simplistic terms, as a key that fits the respective receptor, and that receptor causes a change in the postsynaptic cell (like opening up the membrane to allow molecules in or out) that will ultimately lower or raise the electrical potential of the cell. Remember from last time, that if the potential of the cell is raised above −55mV (or thereabouts) at the axon hillock, an action potential will be generated (the cell will fire down it’s axon).
But how does this process stop once the neurotransmitters have been released into the synaptic cleft?
- One mechanism is to remove the neurotransmitters from the space between neurons. This can happen by “reuptake”: A process whereby the neurotransmitter is taken back into the presynaptic cell terminal by specific transporter sites on the cell. The neurotransmitter is then re-packaged for re-use. For example the monoamine serotonin (5-HT) is taken back up, from the space around the presynaptic terminal, in this manner.
- Another process is degradation, whereby the transmitter (like acetylcholine) is broken down by enzymes and the ‘bits’ are taken up by the presynaptic terminal. Within the presynaptic terminal the neurotransmitter is reassembled for reuse, and repackaged for release once again.
- Another process involves glial cells removing neurotransmitters from the synaptic space to prevent further interaction.
Pharmacology has some cleaver ways of modulating this uptake system to maintain the longevity of a neurotransmitter effect. For example Prozac is designed to interfere with serotonin uptake, in order to keep serotonin in the vicinity of the synaptic cleft. While there remains serotonin to be bound by the presynaptic receptors, the therapeutic effects of serotonin can be enhanced. In fact any drug that has an effect on your mind is either altering an uptake system, or changing specific or multiple neurotransmitters in some way.
AMPA, GABA, and NMDA
In the list above we see that the major neurotransmitters are the amino acid types. Of these, the glutamates bind with activating receptors, namely Alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), and result in very fast activation of the postsynaptic neuron. The GABA neurotransmitters bind with GABA receptors that cause an inhibiting effect on the postsynaptic cell, again a very fast action. These two interactions are seen across the brain and result in much of the fast action of our neural processes—for example much of our thought processes, and sensory input/processing.
There is a slower acting mechanism via a glutamate receptor type know as N-methyl D-aspartate (NMDA). This receptor responds more slowly that the other receptors mentioned above and it is involved in a cascade of events that result in the strengthening of a synapse. This strengthening of the synapse is called long-term potentiation. A strengthened synapse will activate more easily.
Neurotransmitters can also be known as neuromodulators. The distinction is made by the different receptors that either affect the cell from the outside (neurotransmitter) or affect the cell from the inside by initiating a cascade of events within the cell (neuromodulator). A neuromodulating receptor (G-protein-associated receptor), when activated can stimulate the activation of an enzyme in the cell that initiates a ‘second messenger’, and this transmitter inside the cell goes onto produce other actions within the cell to ultimately open or close ion channels in the cell membrane, thus altering the cell potential. One of the important features of this chemical cascade process is that it can lead to activating a protein called a transcription factor that can form new connections and stronger signalling.
What I have explained is an extreme simplification of a complexity of chemical and genetic interactions that are part of the plasticity of the brain. The main points to remember are: 1) Very fast neural signals are orchestrated by AMPA, and GABA receptors, 2) slower receptor activity, that can create synapse strength, works through NMDA sites, and 3) modulating processes within the neuron, via second messenger transmitters, can ultimately lead to new and stronger connections.
There is much more to be said about the qualities of the different neurotransmitters, but rather than go too deeply here, we will wait for specific cases before highlighting the important characteristics of a particular neurotransmitter.
Next time we will have a look at how neurons work together to form activation patterns that make up our perceptions of the world.