In previous article, we've discussed how neurons transmit signals down axons, across the synapse, and to the next dendrite. Today, we will be looking specifically at the synapse and the neurotransmitters released there. These neurotransmitters are essential to brain function and an important part of our journey into neuroscience.
Neurotransmitter
First, what are neurotransmitters? Scientists have come up with characteristics that chemicals must have to be termed a neurotransmitter. They must be produced inside the neuron, found in the axon terminal, and produce an effect on the postsynaptic neuron regardless of method released. [2]
The Process
It all begins with the presynaptic neuron. The signal it has received travels down the axon into the axon terminal, causing the release of calcium. Calcium triggers the release of neurotransmitters into the synapse.
This signal can be transmitted not only from axon to dendrite but also axon to cell body, cell body to cell body and dendrite to dendrite.
Another form of transmission is known as retrograde transmission. In this process, the dendrite of the postsynaptic axon releases neurotransmitters to the axon of the presynaptic neuron. This form of transmission is often used as a way to control the flow of neurotransmitters released from the presynaptic neuron in the regular form of communication. Most times, this change is short lived but it can play a role in long term changes.
Types of Signals
The neurotransmitters released can be inhibitory, excitatory, or modulatory.
Inhibitory neurotransmitters work prevent the postsynaptic neuron from firing.
Excitatory neurotransmitters increase the likelihood that the postsynaptic neuron will fire.
Modulatory neurotransmitters are not released directly into the synapse - but instead a wider area. They can affect more than one neuron. They effect slower, wide reaching changes.
Neurotransmitters such as acetylcholine can change the signal they impart on the postsynaptic neuron based on the type of receptor they bind to.
As the postsynaptic neuron has a multitude of dendrites and receptors, it can receive more than one signal at a time. The signals received can be summed up in two ways.
Spatial summation:
multiple impulses are received at different dendrites on the neuron and then summed up
Temporal summation:
multiple impulses are received within a short period of time and then summed up
If the resulting signal is large enough to reach the threshold potential, the neuron fires.
Types of receptors
Neurotransmitters that have crossed the synapse bind to receptors on the postsynaptic neuron. There are two main types of receptors; each has different effects on the neuron.
Ionotropic:
Once activated, these receptors open ion channels, such as potassium and sodium. They cause a rapid, short lasting change in the postsynaptic neuron
Metabotropic:
Once activated, the g protein activates another protein on the membrane. This catalyzes a secondary response within this cell. This chain of events is significantly slower yet longer lasting.
Removal
Once the neurotransmitters are released, they need to be removed to avoid clogging the synapse. If they are not quickly removed, then rapid, repeated activation of neurons (the basis of cognitive functioning) is not possible.
This occurs through: reuptake, destruction, and diffusion.
Reuptake:
Neurotransmitters are be pumped back to the presynaptic cell's axon terminal for reuse in the future. This process is often affected by drugs - causing more dopamine, or other neurotransmitter affected, to build up in the synapse.
Destruction:
Neurotransmitters can also be degraded by enzymes released into the synapse.
Diffusion:
Occasionally, neurotransmitters will simply spread into the surrounding area, clearing the synapse for the next signal.
Specific Neurotransmitters
Acetylcholine
- First known neurotransmitter - discovered over 80 years ago
- Function:
- Voluntary muscles
- Acetylcholine opens Na+ channels in the myocyte causing contraction
- Controlling Heartbeat
- Cognitive Function (the mechanism behind this function remains unknown)
- Can be excitatory or inhibitory depending on what receptor it binds to
- Can be found in both the central and peripheral nervous systems
- Linked to Alzheimer's disease (see below)
GABA
- Amino acid
- Primary inhibitory neurotransmitter in the nervous system
- Functions:
- vision
- motor control
- regulation of anxiety
- Derived from glutamate
- Benzodiazepines increase the efficiency of GABA
- Linked to huntington's disease (see below)
Serotonin
- Monoamine
- Found in various parts of the nervous system
- Made in the raphe nucleus, midline neurons of pons and upper brain stem
- Also produced in the gastrointestinal tract in response to food
- Functions:
- Sleep
- Memory
- Appetite
- Mood
- Antidepressant medications often inhibit serotonin reuptake mechanisms - leaving serotonin in the synapse for longer thereby prolonging its positive effects on mood
ATP
- Found in the central and peripheral nervous systems
- Functions:
- autonomic control
- sensory transduction
- communication with glial cells
Dopamine
- monoamine
- catecholamine
- neuromodulator
- Functions:
- motor control
- reward system
- coordination of body movements
- motivation
- found in the peripheral nerve fibers and central neurons (substantia nigra, midbrain, ventral tegmental area, and hypothalamus)
- drugs often increase levels of dopamine in the brain
- Linked to Parkinson's disease (see below)
Norepinephrine
- monoamine
- catecholamines
- Functions:
- control blood pressure
- heart rate
- liver function
- alertness in fight or flight situations
- levels are highest during danger or stress, lowest during sleep
- produced by central neurons (locus caeruleus and hypothalamus)
Glutamate
- amino acid
- primary excitatory neurotransmitter in the brain
- Functions:
- memory
- learning
- excess level of glutamate results in high cellular toxicity and even death (these conditions are often see in alzheimer's, stroke, and seizures)
- found in the cortex, cerebellum, and spinal cord
- nitric oxide increases cellular response to glutamate
Endorphins
- natural response to pain - blocking the signal
- can be triggered by exercise
- activates hypothalamus, amygdala, thalamus, locus caeruleus
Glycine
- inhibitory neurotransmitter
- normally found in the renshaw cells of the spinal cord
- Function:
- relax antagonist muscles
Histamine
- monoamine
- Functions:
- metabolism
- temperature control
- regulates hormones
- controlling sleep wake cycle
Oxytocin
- hormone as well as a neurotransmitter
- produced by hypothalamus
- Functions:
- social recognition
- bonding
- reproduction (uterine contractions)
Nitric oxide
- gas
- Functions:
- smooth muscles relaxing
- dilating blood vessels
- stimulated by neurotransmitters that increase intracellular calcium
Substance P
- a peptide
- occurs in central neurons (such as the habenula, substantia nigra, basal ganglia, medulla, and hypothalamus), particularly the dorsal root ganglia.
- triggered by intense afferent painful stimuli
- Functions:
- modulates the neural response to pain and mood
- modulates nausea and vomiting through the activation of NK1A receptors that are localized in the brain stem.
These are only descriptions of some main neurotransmitters - there are over a hundred recognized neurotransmitters.
Diseases (affected by neurotransmitters)
Depression: abnormalities in acetylcholine neurons, noradrenergic, dopaminergic and serotonergic transmission
Brain injury: stimulates release of excitatory neurotransmitters causing excess intracellular calcium, which eventually leads to neuronal death
Seizure: can be caused by increased glutamate or reduced GABA
Huntington's disease: a mutation on chromosome 4 causes excess huntingtin and excess cellular stimulation. In addition, GABA producing neurons degenerate.Treatment: block NMDA receptors to prevent effects of excess glutamate
Mania: increased norepinephrine and dopamine
Botulism: inhibition of acetylcholine release from motor neurons
Myasthenia gravis: causes inactivation of acetylcholine receptors, and postsynaptic histochemical changes at the neuromuscular junction due to autoimmune reactions, leading to reduced muscle function.
Schizophrenia: increased presynaptic release of dopamine and sensitivity to dopamine
parkinsons: loss of dopaminergic neurons in the substantia nigra and other areas of the brain
Alzheimer's: neurofibrillary tangles and plaques in the areas of the cortex that use and produce acetylcholine, causing degeneration of the neurons and decrease in acetylcholine levels
[1] Brain Facts: A primer on the brain and nervous system
[7] https://www.merckmanuals.com/professional/neurologic-disorders/neurotransmission/neurotransmission
Blog by : Lasya Kambhampati
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