The synapse is the small gap separating two neurons, the presynaptic neuron and postsynaptic neuron. It separates the axon terminals of the presynaptic neuron from the postsynaptic neuron. The synapse is made of three major parts: a presynaptic ending, a postsynaptic ending, and a synaptic cleft. The presynaptic ending contains the neurotransmitters, mitochondria, endoplasmic reticulum, and other cell organelles. The postsynaptic ending contains receptor sites for the neurotransmitters in the presynaptic ending. The synaptic cleft is the space between the presynaptic and postsynaptic endings.
The arrival of an action potential normally causes the release of neurotransmitters from the presynaptic neuron. The action potential travels down to the axon terminal of the presynaptic neuron. Each axon terminal becomes swollen forming a presynaptic knob. There is a depolarization of the presynaptic membrane resulting from the action potential. This depolarization causes an increase in the permeability to sodium and calcium ions. The presynaptic knob is then filled with membrane-bound vesicles; each filled with a neurotransmitter. Calcium ions then flood into the presynaptic knob by means of diffusion. The influx of calcium ions triggers the exocytosis of the synaptic vesicles. The neurotransmitters are then released into the synaptic cleft. The transmitters travel across the synaptic cleft towards the receptors (which are chemically regulated channels or ligand-gated ion channels) by means of diffusion.
There are two main categories of transmissions, excitatory transmissions and inhibitory transmissions. Excitatory transmissions occur when the neurotransmitter at a synapse depolarizes the postsynaptic membrane. Chemically regulated channels are the receptors where the neurotransmitters bind to at the postsynaptic membrane. Inhibitory transmissions occur when the neurotransmitter at a synapse hyperpolarizes the postsynaptic membrane, which causes the transmembrane potential to be farther from the threshold. The threshold is the transmembrane potential where an action potential begins. This increased membrane potential is called an inhibitory postsynaptic potential(IPSP). It is inhibitory, because now there must be a stronger depolarization in order for the membrane potential to return to the threshold.
Cholinergic transmissions are a type of excitatory transmission. The cholinergic transmission involves the release of the neurotransmitter, acetylcholine(ACh). There are 4 basic steps in a cholinergic transmission:
Step 1: The action potential travels down to the axon terminal of the presynaptic neuron. Each axon terminal becomes swollen, forming a postsynaptic knob. There is a depolarization of the presynaptic membrane as a result from the action potential. This depolarization causes and increase in the permeability to sodium and calcium ions. The presynaptic knob is then filled with membrane-bound vesicles; each filled with ACh. Calcium ions then flood into the presynaptic knob by means of diffusion.
Step 2: The crowd of calcium ions triggers the exocytosis of the synaptic vesicles. ACh is then released into the synaptic cleft. The ACh molecules travel across the synaptic cleft towards the receptors of the postsynaptic ending by means of diffusion.
Step 3: The release of ACh stops shortly as calcium ions are quickly removed from the cytoplasm. Chemically regulated channels, also called ligand-gated ion channels, are the ACh receptors at the postsynaptic membrane. The ACh molecules then bind to these receptors, resulting in increased sodium permeability, which reduces the membrane potential. This reduced membrane potential is called an excitatory postsynaptic potential or EPSP. The EPSP produced by one cholinergic transmission isn't enough to reach the threshold of the postsynaptic neuron. When the EPSP produced isn't enough to reach the threshold of the neuron, the neuron is called a facilitated neuron. Many EPSP's created in a series, added together, can reach the threshold of the neuron. The series of EPSPs added together is the process of summation. If the threshold is reached, then an action potential is generated. There is a synaptic delay within the arrival of stimuli at the presynaptic knob and the result of the stimuli on the postsynaptic membrane. This delay is about 0.2 to 0.5 milliseconds long. The synaptic delay is a result of the increased concentration of calcium ions and the release of the ACh.
Step 4: Acetylcholinesterase(AChE) breaks down all of the ACh in the synaptic cleft and removes it from the postsynaptic ending. The AChE does this by hydrolyzing the ACh molecules into acetate and choline. The presynaptic knob then absorbs the choline from the synaptic cleft. The choline molecules are used to reintegrate ACh. When ACh molecules are recycled, the recycling and transport mechanisms may not be able to keep up with the neurotransmitter. This results in synaptic fatigue, where the synapse is idle until ACh is replenished.
Adrenergic transmissions are also a type of excitatory transmission. Adrenergic transmissions involve the release of the neurotransmitter, norepinephrine(NE). Adrenergic begins with the arrival of an action potential. This results in the depolarization of the presynaptic knob. Calcium ions then flood into the cytoplasm, which causes NE to be released into the synaptic cleft. NE crosses the synaptic cleft by means of diffusion and binds to the receptors at the postsynaptic membrane. This activates adenyl cyclase, which changes ATP into cyclic-AMP(cAMP). NE is the first messenger and cAMP is the second messenger. Cytoplasmic enzymes, activated by cAMP, then open the chemically regulated gated channels and sodium ions flood in. This causes depolarization of the postsynaptic membrane. The membrane potential isn't effected very much, because phosphodiesterase, another cytoplasmic enzyme, changes cAMP to an idle AMP. NE is rapidly removed from the synapse from getting absorbed by the synaptic terminal, diffusing out of the area, or getting broken down from catecholO-methyltransferase(COMT) or monoamine oxidase(MAO).
Gamma amino-butyric acid(GABA), dopamine(DOPA), and serotonin are all CNS transmitters. GABA is a type of inhibitory transmitter. The binding of GABA to receptors on the postsynaptic neuron opens ligand-gated chloride channels and activates a G protein that leads to the opening of potassium channels. This results in the facilitated diffusion of ions, with chlorine going in and potassium going out, which increases the membrane potential(IPSP). Dopamine is also a type of inhibitory transmitter, which means that it hyperpolarizes the transmembrane potential and raises its membrane potential away from the threshold. Dopamine plays a major role in addiction, as it affects the brain processes that control pain, pleasure, movement, and response to emotions. Serotonin is yet another inhibitory neurotransmitter, meaning it also hyperpolarizes the transmembrane potential. The hyperpolarized neuron only appears to have an increased threshold, but the actual voltage has actually stayed the same. It is just a matter of whether the depolarization by the excitatory synapses can reach the threshold.
Medicinal drugs have different effects on synapses and the nervous system overall. Morphine, a pain killer, binds to enkephalin receptors, which are receptors involved in transmitting pain signals back to the brain. The morphine hyperpolarizes the postsynaptic membrane, which prevents the enkephalins from transmitting pain signals. Novocaine, an anesthetic, affects ACh at synapses, because it reduces sodium permeability in the membrane. This stops the stimulation of sensory neurons. Succinylcholine, which is used to relax muscles during surgery, reduces the sensitivity to acetylcholine. This causes the temporary paralysis of voluntary muscles. Neostigmine, which is used to balance overdoses of tubocurarine, prevents cholinesterase from inactivating ACh. This results in the sustained contraction of skeletal muscles. Barbiturates, used as a sedative and anesthetic, can prevent seizures as well. They decrease the rate of ACh released, and also bind to GABA receptors. It increases the resting potential, which makes it less likely to fire. The effect is muscular weakness and a decline in CNS activity.
Recreational drugs have different effects on synapses and the nervous system as well. Nicotine, the ingredient that makes cigarettes addictive and harmful, binds to ACh receptors. Small amounts of nicotine promote voluntary muscles, and large amounts cause paralysis. Marijuana's active ingredient, tetrahydrocannabinol(THC) binds to CB1 receptors on the postsynaptic membranes in parts of the forebrain and spinal cord. THC causes drowsiness, lower sensitivity to pain, and a decrease in alertness. In high doses, it can cause perception distorting symptoms. Heroin is an opiate that blocks pain signals. It binds to the enkephalin receptors, which are the receptors involved in transmitting pain signals, and prevents the enkephalins from transmitting pain signals to the brain. Methylenedioxymethamphetamine or ecstasy is a synthetic psychedelic drug. It binds to serotonin receptors in the postsynaptic ending, distorting the perception of the senses, especially sight and sound. Isofluorane, a fluorinated hydrocarbon, is taken into the body by inhaling. It binds to GABA receptors, decreasing the sensitivity to postsynaptic neurons.
By: Kevin Chao- June 19, 2001