When an action potential reaches the axon terminal, it generally stops there, although information is transmitted from a neuron to another cell at a synapse.
a. Synapses are small spaces between neurons, between neurons and effectors, or between neurons and sensory receptors.
b. The presynaptic neuron synthesizes the neurotransmitter and packages it in synaptic vesicles, which are stored in the neuron’s synaptic terminals.
c. When an action potential reaches a terminal, it depolarizes the terminal membrane, opening voltage-gated calcium channels in the membrane.
i. Calcium ions (Ca2+) then diffuse into the terminal, and the rise in Ca2+ concentration in the terminal causes some of the synaptic vesicles to fuse with the terminal membrane, releasing the neurotransmitter.
ii. The neurotransmitter diffuses across the narrow gap, called the synaptic cleft, which separates the presynaptic neuron from the postsynaptic cell.
d. Neurotransmitters are chemicals that bind to receptors on the post-synaptic membrane and trigger the opening of gates. There are over 100 currently known.
i. Some neurotransmitters are excitatory.
(1) The binding of neurotransmitter to postsynaptic receptors opens gated channels that allow Na+ to diffuse into the cell, increasing the membrane potential toward threshold.
ii. Some neurotransmitters are inhibitory.
(1) The binding of neurotransmitter to postsynaptic receptors open gated channels that allow K+ to exit the cell, decreases the membrane potential away from threshold.
iii. Acetylcholine is one of the most common neurotransmitters in both invertebrates and vertebrates.
(1) In the vertebrate CNS, it can be inhibitory or excitatory, depending on the type of receptor. For instance, it has an excitatory effect on most muscle cells but is inhibitory to cardiac muscle cell contraction. Acetylcholine in the CNS it tends to help us filter out weak stimuli while amplifying stronger ones
iv. Dopamine is associated with the reward system but is believed to be active mostly in the anticipation of reward and reward-seeking behavior. It might be involved in learning to associate new behavior with a reward. Dopamine is normally released when a need is filled, causing a feeling of pleasure or satisfaction.
v. Serotonin has several functions in the CNS, including the regulation of mood (feeling of happiness), appetite, sleep. Serotonin also has some cognitive functions, including memory and learning. Serotonin is synthesized from the amino acid tryptophan - likely where the myth about becoming sleepy after eating turkey originated.
e. Imbalances in neurotransmitters are associated with several disorders.
(1) Parkinson’s disease is associated with a lack of dopamine in the brain while schizophrenia might be related to high dopamine.
(2) Depression has been linked to low serotonin and norepinephrine.
f. A drug is any substance, other than food, that changes the structure or function of the body. Some drugs produce the desired effect by interfering with the normal activity of neurotransmitters.
i. Stimulants (e.g., amphetamines like meth and ecstasy, cocaine) increase the actions regulated by the nervous system by blocking the removal of dopamine from the synaptic cleft. In the autonomic nervous system they increase the effect of norepinephrine (a neurotransmitter involved in the fight-or-flight response). Some of these are strong enough stimulants to increase the heart rate and blood pressure significantly enough to cause death.
(1) Once the drug wears off, the supply of neurotransmitters is depleted and depression results.
(2) Adenosine has a sedative effect because it inhibits the release of stimulating neurotransmitters. Caffeine occupies adenosine receptors, blocking its effect.
ii. Depressants (barbiturates, tranquilizers), tend to enhance the neurotransmitters that inhibit neurons. Many mimic GABA, the main inhibitory neurotransmitter in the CNS. This calms the parts of the brain that sense fear and having a relaxing effect. Continued use creates a dependency in which the user cannot cope with normal anxiety without the drug.
(1) Heroine is a pain-relieving sedative.
(2) Blocking the breakdown of serotonin at synapses is the method of action of many antidepressants.
(a) Prozac inhibits the uptake of serotonin after its release, increasing its effect.
(3) Alcohol is a depressant that slows down the function of the CNS. Ethanol binds to acetylcholine, GABA, serotonin, and NMDA receptors. Blocking NMDA receptors results in hallucinations, paranoid delusions, confusion, difficulty concentrating, agitation, alterations in mood, nightmares, catatonia, ataxia, anaesthesia, and learning and memory deficits.
iii. Nicotine inhibits the enzymes that breakdown dopamine and serotonin, resulting in feelings of pleasure and relaxation. It binds to the same receptors as acetylcholine, resulting in the wide range of effects reported (alertness, relaxation, increased concentration and memory).
iv. LSD binds to serotonin and dopamine receptors and blocks the inhibitory effect which causes hallucinations (acid trip). The complete mechanism of action is unknown.
v. Opiates (morphine, codeine) mimic the effects of endorphins. The body quickly adjusts to the higher level of endorphins so that withdrawal includes intense pain and sickness.
(1) Endorphins are natural analgesics (pain killers). They block the release of GABA and increase the release of dopamine. They also block pain signals.
vi. THC in marijuana signals the presynaptic neurons that they have sent a message when in reality they have not. THC can thus exert both excitatory and inhibitory effects (by inhibiting the release of both the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate). This explains the sedation and euphoria that it causes.