Structure of a Neuron
A neuron consists of a central cell body which constitutes the nucleus, mitochondria, endoplasmic reticulum and golgi apparatus. Cell processes which carry the signals towards the nucleus are called the dendrites, while the one which carries the signals away from the cell body is termed as the axon. Axon forms telodendria and synaptic terminals.
A neuron may terminate into:
- A muscle, causing it to contract
- A gland, resulting in production of secretions
- Another neuron, to pass along the nervous signals. The junction between the two neurons is called synapse. The neuron that carries the signal to the other neuron is called pre-synaptic neuron, while the other neuron is called the post-synaptic neuron. The space between the two neurons is called the synaptic cleft.
Types of synapses
A synapse can be either electrical or chemical.
- In an electrical synapse, the two neurons are connected through charge carrying ions, which flow between them in the gap junctions. Although it is an unbroken way of transmission of signals, it is essentially either ‘on’ or ‘off.’ These synapses are unregulated. If one neuron is activated via an action potential, the second neuron will definitely be activated. Such synapses are rare in the human nervous system, however, found in specialized locations such as pulp of the tooth and retina of the eye.
- Chemical synapse consists of the release of specific chemical substances into the synaptic cleft, after an action potential reaches the end of the pre-synaptic neuron. These chemical substances are called neurotransmitters and are contained in vesicles of the synaptic knob, a swelling at the end of the pre-synaptic neuron. Chemical synapses are abundantly present in the human nervous system and therefore described in detail below.
Signal transmission across a synapse
- When an action potential reaches the end of the pre-synaptic neuron, it causes specific changes in the cell membrane, which leads to opening of voltage gated calcium channels in the synaptic knob.
- Calcium ions being in excess amount in the extracellular fluid move down the concentration gradient into the synoptic knob.
- The calcium ions cause a release of neurotransmitters in the synaptic cleft. The vesicles containing neurotransmitters move towards the cell membrane, fuse with it and are released by the process of exocytosis.
- The neurotransmitters bind to their specific receptors on the sub-synaptic membrane, which is the portion of the post-synaptic membrane lying immediately below the synaptic knob.
- The receptors are an integral part of specific ion channels on the post-synaptic membrane. Binding of the neurotransmitters to their receptors open up these channels. This changes the ion permeability of the cell membrane.
- The synapse is unidirectional i.e. from pre-synaptic neuron to the post-synaptic neuron as the former releases the neurotransmitters and the later has receptors on its cell surface membrane. The pre-synaptic neuron releases only one type of neurotransmitter.
- The conversion of this chemical signal back to an electrical signal requires time, often referred to as the synaptic delay. It is usually about 0.5 – 1msec. As the pathway becomes more and more complex, the total synaptic delay also increases which causes a longer reaction time. The figure illustrates the signal transmission across a synapse.
As long as the neurotransmitters remain bound to the receptors, the potential change produced in the post-synaptic membrane continues. However, in order to receive a new synapse, the neurotransmitters must first be removed from the receptor site and the synaptic cleft.
These neurotransmitters are either taken up by the pre-synaptic neuron, to be stored and released for another signal transmission (see figure), or they are inactivated by the enzymes present in the synaptic cleft. The response therefore produced by the neurotransmitters is terminated.
Types of synapse depending upon the permeability changes in the post-synaptic neuron
There are two types of synapse depending upon the permeability changes in the post-synaptic membrane. It could either be an excitatory synapse or an inhibitory synapse.
In an excitatory synapse, the sodium and potassium ions are opened up in the post-synaptic membrane. The permeability of these ions increases, however, their net movement depends upon their electro-chemical gradient across the cell membrane.
At resting membrane potential, the concentration of sodium ions is abundantly higher in the extracellular fluid, therefore, sodium ions diffuse into the postsynaptic neuron. Potassium ions, on the other hand, are already in excess inside the cell; therefore, only a few of them leak out of the cell as the movement of sodium ions changes their permeability across the membrane.
The net movement of positive ions inside the cell changes the membrane potential to a less negative value. A single excitatory synapse only produces a small depolarization in the post-synaptic neuron and does not reach the threshold value. The action potential in the post-synaptic neuron is only generated if the threshold value is reached when many excitatory inputs are given.
In an inhibitory synapse, the neurotransmitters released cause the opening of potassium and chloride ion channels. Potassium ions being more abundant diffuse out of the post-synaptic neuron. Chloride ions are abundant in the extracellular fluid, therefore, diffuse into the post-synaptic neuron. This increases the negativity inside the cell and the cell membrane is said to be hyper-polarized.
The hyper-polarization of the cell membrane moves it further away from the threshold potential, thereby minimizing the generation of action potential in this neuron.
The net charge across the cell membrane of the post-synaptic neuron is composite of all the excitatory and the inhibitory synapses, as shown in the figure. It is known as grand post-synaptic potential (GPSP). The action potential in the post-synaptic neuron is generated at the axon hillock as it has the lowest threshold potential, due to the presence of abundant sodium channels.
Some neurotransmitters, such as glutamate, produce excitatory post-synaptic potential while others, such as gamma amino butyric acid (GABA), produce inhibitory post-synaptic potential.
As mentioned earlier, a single excitatory synapse is not enough to produce excitatory post-synaptic potentials. Summation is a process by which several pre-synaptic signals are summed up to produce an action potential in the post-synaptic neuron. Depending upon the number of signals, the magnitude of the response varies. There are two types of summation: temporal summation and spatial summation.
Temporal summation is the process in which the pre-synaptic neuron generates action potentials in very close succession. The post-synaptic membrane becomes depolarized due to the first action potential of the pre-synaptic neuron.
As the second action potential generated in the pre-synaptic membrane causes further depolarization in the post-synaptic membrane, the later reaches the threshold potential; thus, an action potential is generated in the post-synaptic neuron.
Sometimes, up to 50 excitatory post-synaptic potentials are required to generate an action potential. The frequency of action potentials generated in the pre-synaptic neuron is decisive of the number of neurotransmitters released and the magnitude of depolarization in the post-synaptic membrane.
Spatial summation is the process in which simultaneous action potential in several presynaptic neurons releases a large number of neurotransmitters into the synaptic cleft. The magnitude of depolarization generated in the post-synaptic neuron reaches the threshold potential and an action potential is generated. The figure beside gives an outline of the process of summation.
Convergence and divergence
- Convergence is the property of neuron in which a single neuron receives input signals from a number of neurons, due to the presence of several dendritic branches.
- Divergence is when a single neuron sends input signals to many other neurons. The branching of axon facilitates divergence.
Applied Clinical Physiology
Selective serotonin reuptake inhibitors (SSRIs) are a group of anti-depressant drugs which block the reuptake of serotonin neurotransmitter by the pre-synaptic neuron. Serotonin therefore remains in the synaptic cleft for a longer duration of time. This prolongs its effect on the post-synaptic neuron, thereby minimizing anxiety symptoms.
Cocaine, a common substance of abuse, blocks the reuptake of neurotransmitter dopamine. It competitively binds to the dopamine reuptake transporter, which prolongs the duration of dopamine in the synaptic cleft. The abuser gets a continuous pleasure sensation.
The post-synaptic neurons become desensitized to the level of dopamine and eventually require a greater amount for the generation of action potential. This explains the strong addiction to cocaine. With a prolonged use of cocaine, the number of dopamine receptors is also reduced on the post-synaptic membrane.
Myasthenia gravis is an autoimmune disease in which there is a production of auto-antibodies against acetylcholine receptors on the post-synaptic membrane. These receptors are blocked, causing failure of muscle contraction.
Patients complain of exhaustion and fatigue as the day ends. The classical symptom is the drooping of the eyelids as the night time approaches. The symptoms are treated with acetylcholine-esterase inhibitors.
Acetylcholine-esterase is an enzyme present in a normal individual which breaks down the acetylcholine neurotransmitter in the synaptic cleft. Blocking this enzyme will increase the level of acetylcholine in the synaptic cleft which will compete with the auto-antibodies.
Parkinson’s disease is a neurodegenerative disorder in which the production of dopamine is decreased due to destruction of the cells producing it. This results in symptoms such as hypokinesia, rigidity, dementia, hallucinations and depression. The disease is treated with levodopa, dopamine agonists and monoamine oxidase B (MA0-B) inhibitors. MAO-B is an enzyme that causes the destruction of dopamine in the synaptic cleft.
Tetanus toxin prevents the release of GABA, an inhibitory neurotransmitter. This results in unchecked excitatory signals to the skeletal muscles which go into spasm. The jaw muscles are specifically affected giving the classical sign of ‘lockjaw.’ As the disease progresses, the respiratory muscles also get involved causing death.
Strychnine poison binds to the glycine receptors on the post-synaptic neuron. Glycine is an inhibitory neurotransmitter. When it does not bind to its receptors on the post-synaptic membrane, the post-synaptic inhibition is abolished resulting into unchecked excitatory pathways. The patient dies of convulsions and muscular spasm.