•
Chapter 3
Synapses
•
The Concept of the Synapse
•
Neurons communicate by transmitting chemicals at junctions called “synapses”
•
In 1906, Charles Scott Sherrington coined the term synapse to describe the specialized gap that
existed between neurons.
•
Sherrington conducted his research investigating how neurons communicate with each other by
studying reflexes (automatic muscular responses to stimuli).
•
The Concept of the Synapse
•
Sherrington observed three important points about reflexes:
1. Reflexes are slower than conduction along an axon.
2. Several weak stimuli presented at slightly different times or slightly different locations
produces a stronger reflex than a single stimulus does.
3. As one set of muscles relaxes, another set becomes excited.
•
The Concept of the Synapse
•
Sherrington observed a difference in the speed of conduction of the reflex arc from that of the
speed of an action potential.
•
He believed the difference must be accounted for by the time it took for communication
between neurons to occur.
•
Evidence validated the idea of the synapse.
•
The Concept of the Synapse
•
Sherrington observed that repeated stimuli over a short period of time produced a stronger
response.
•
Led to the idea of temporal summation or that repeated stimuli can have a cumulative effect
and can produce a nerve impulse when a single stimuli is too weak.
•
The Concept of the Synapse
•
Sherrington also noticed that several small stimuli on a similar location produced a reflex when a
single stimuli did not.
•
This led to the idea of spatial summation or that synaptic input from several locations can have a
cumulative effect and trigger a nerve impulse.
•
The Concept of the Synapse
•
Sherrington also noticed that during the reflex that occurred, the foot of a dog that was pinched
retracted while the other three feet were extended.
•
He suggested that an interneuron in the spinal cord sent an excitatory message to the flexor
muscles of one leg and an inhibitory message was sent to the other three legs.
•
The Concept of the Synapse
•
This led to the idea of inhibitory postsynaptic potential or the temporary hyperpolarization of a
membrane.
•
An IPSO occurs when synaptic input selectively opens the gates for positively charged potassium
ions to leave the cell or for negatively charged chloride ions to enter the cells.
•
Serves as an active “brake”, that suppresses excitation.
•
The Concept of the Synapse
•
Neurons can have thousands of synapses.
•
Both temporal and spatial summation can occur within a neuron.
•
The likelihood of an action potential depends upon the ratio of IPSPs to EPSPs at a given
moment.
•
Concept of Synapse
•
Chemical Events at the Synapse
•
Transmission of a message across the synapse occurs by chemical means.
•
Neurotransmitters are chemicals that travel across the synapse and allow communication
between neurons.
•
Chemical Events at the Synapse
The major sequence of events that allow communication between neurons across the synapse are as
follows:
1. The neuron synthesizes chemicals that serve as neurotransmitters.
2. Neurons store neurotransmitters in axon terminals or transport them there.
3. An action potential triggers the release of neurotransmitters into the synaptic cleft.
4. The neurotransmitters travel across the cleft and attach to receptors on the postsynaptic
neuron.
5. The neurotransmitters separate from the receptors.
6. The neurotransmitters are taken back into the presynaptic neuron, diffuse away, or are
inactivated by chemicals.
7. The postsynaptic cell may send negative feedback to slow the release of further
neurotransmitters.
•
•
Chemical Events at the Synapse
Major categories of neurotransmitters include the following:
–
Amino acids.
–
Peptides.
–
Acetylcholine.
–
Monoamines.
–
Purines.
–
Gases.
•
Chemical Events at the Synapse
•
Neurons synthesize neurotransmitters and other chemicals from substances provided by the
diet.
–
Catecholimines are synthesized and contain a catechol group and an amine group.
–
Acetylcholine is synthesized from choline found in milk, eggs, and nuts.
–
Serotonin uses tryptophan to be synthesized that is found in turkey.
•
Chemical Events at the Synapse
•
Smaller neurotransmitters are synthesized in the presynaptic terminal and held there for
release.
–
•
Example: acetylcholine
Larger neurotransmitters are synthesized in the cell body and transported down the axon.
–
Example: peptides
•
Chemical Events at the Synapse
•
Small molecule NT
•
Synthesized in the presynaptic terminal
•
Congregate close to the terminal wall
•
Are released in one shot
•
Have faster but shorter effects
•
Example: GABA
•
Large molecule NT
•
Synthesized in the presynaptic cell body
•
Congregate away from the terminal wall
•
Are released more slowly
•
Have longer lasting effects
•
Example: peptides
•
Chemical Events at the Synapse
•
Vesicles are tiny spherical packets located in the presynaptic terminal where neurotransmitters
are held for release.
•
Exocytosis refers to the excretion of the neurotransmitter from the presynaptic terminal into
the synaptic cleft.
–
Triggered by an action potential arriving from the axon.
•
Chemical Events at the Synapse
•
Transmission across the synaptic cleft by a neurotransmitter takes fewer than 10 microseconds.
•
Most individual neurons release at least two or more different kinds of neurotransmitters.
•
A neuron may respond to more types of neurotransmitters than it releases.
•
Chemical Events at the Synapse
•
An ionotropic effect refers to when a neurotransmitter attaches to receptors and immediately
opens ion channels.
•
Ionotropic effects occur very quickly and are very short lasting.
•
Most of the brain’s excitatory ionotropic synapses use glutamate or acetylcholine as a
neurotransmitter.
•
Chemical Events at the Synapse
•
Metabotropic effects refer to when a neurotransmitter attaches to a receptor and initiates a
sequence of metabolic reactions that are slower and longer lasting.
•
Metabotropic events include such behaviors as hunger, fear, thirst, or anger.
•
When neurotransmitters attach to a metabotropic receptor, it bends the rest of the protein .
•
Bending allows a portion of the protein inside the neuron to react with other molecules.
•
Chemical Events at the Synapse
•
The portion inside the neuron activates a G-protein –one that is coupled to guanosine
triphosphate (GTP), an energy storing molecule.
•
G-protein increases the concentration of a “second-messenger”.
•
The second messenger communicates to areas within the cell.
–
May open or close ion channels, alter production of activating proteins, or activate
chromosomes.
•
Chemical Events at the Synapse
•
Metabotropic effects utilize a number of different neurotransmitters and are often called
neuromodulators because they do not directly excite or inhibit the postsynaptic cell.
•
Instead, neuromodulators:
–
increase or decrease the release of other neurotransmitters
–
alter the response of postsynaptic cells to various inputs.
•
Chemical Events at the Synapse
Hormones
•
A hormone is a chemical secreted by a gland or other cells that is transported to other organs by
the blood where it alters activity.
•
Endocrine glands are responsible for the production of hormones.
•
Hormones are important for triggering long-lasting changes in multiple parts of the body.
•
Chemical Events at the Synapse
Hormones
•
The hypothalamus maintains a fairly constant circulating level of hormones through a negativefeedback system.
–
Example : TSH- releasing hormone
•
Chemical Events at the Synapse
Clean up
•
Neurotransmitters released into the synapse do not remain and are subject to either
inactivation or reuptake.
•
Reuptake refers to when the presynaptic neuron take sup most of the neurotransmitter
molecules intact and reuses the.
–
Example: Serotonin is taken back up into the presynaptic terminal.
•
Chemical Events at the Synapse
Clean up
•
Examples of inactivation and reuptake include:
–
•
Acetylcholine is broken down by acetylcholinesterase into acetate and choline.
Some serotonin and catecholamine molecules are converted into inactive chemicals:
–
COMT and MAO are enzymes that convert catecholamine transmitters into inactive
chemicals.
•
Chemical Events at the Synapse
Drugs
•
Research has begun to investigate the role of events at the synapse and their effects on
personality.
•
Research suggests that some dopamine receptors may be related to “pleasure-seeking” and
“thrill-seeking” behaviors.
•
Substance Abuse and Addictions
•
Addictive substances increase dopamine activity in certain areas of the brain.
•
Olds and Milner (1954) placed rats in a Skinner box that allowed self-stimulation of the brain by
the pressing of a lever.
•
Rats sometimes pressed the lever 2000 times per hour to stimulated the release of dopamine in
the nucleus accumbens.
•
Substance Abuse and Addictions
•
Other behaviors that release dopamine include sexual excitement, gambling, and video games.
•
fMRI research indicates dopamine is released during viewing of “attractive” people.
•
Activity in the nucleus accumbens seems to be related to “wanting”.
–
Results in a monopolization of attention.
•
Drugs and the Synapse
•
The study of the influence of various kinds of drugs has provided us with knowledge about many
aspects of neural communication at the synaptic level.
•
Drugs work by mimicking our own neurochemistry.
–
Example: receptors in the brain respond to LSD and cocaine
•
Drugs alter various stages of synaptic processing.
•
Drugs and the Synapse
•
Drugs either facilitate or inhibit activity at the synapse.
–
Antagonistic drugs block the effects of neurotransmitters.
–
Agonist drugs mimic or increase the effects of neurotransmitters.
•
Drugs and the Synapse
•
Drugs work by doing one or more of the following to neurotransmitters:
–
Increasing the synthesis.
–
Causing vesicles to leak.
–
Increasing release.
–
Decreasing reuptake.
–
Blocking the breakdown into inactive chemical.
–
Directly stimulating or blocking postsynaptic receptors.
•
Drugs and the Synapse
•
A drug has an affinity for a particular type of receptor if it binds to that receptor.
–
•
Can vary from strong to weak.
The efficacy of the drug is its tendency to activate the receptor.
•
Drugs can have a high affinity but low efficacy. This happens when a drug binds easily to a
receptor but fails to stimulate it. In this case the drug has antagonist effects.
•
Drugs and the Synapse
•
Almost all abused drugs stimulate dopamine release in the nucleus accumbens,
–
small subcortical area rich in dopamine receptors
–
an area responsible for feelings of pleasure
•
Sustained bursts of dopamine in the nucleus accumbens inhibit cells that release the inhibitory
neurotransmitter GABA
•
Drugs and the Synapse
•
Drugs are categorized according to their predominant action or effect upon behavior
•
Stimulant drugs increase excitement, alertness, motor activity and elevate mood.
•
Examples: amphetamines, cocaine, methylphenidate (Ritalin), MDMA (Ecstasy), nicotine
•
Stimulant drugs directly stimulate dopamine receptor types D2, D3, and D4.
•
Drugs and the Synapse
•
Amphetamine stimulate dopamine synapses by increaseing the release of dopamine from the
presynaptic terminal.
•
Cocaine blocks the reuptake of dopamine, norepinephrine, and serotonin.
•
Methylphenidate (Ritalin) also blocks the reuptake of dopamine but in a more gradual and more
controlled rate.
–
Often prescribed for people with ADD
•
Drugs and the Synapse
•
Ecstasy (MDMA) increases the release of dopamine at low doses that account for its stimulant
properties.
•
Ecstasy increases the release of serotonin at higher doses accounting for its hallucinogenic
properties.
•
Research indicates ecstasy use may contribute to higher incidences of anxiety and depression as
well as memory loss and other cognitive deficits.
•
Drugs and the Synapse
•
Nicotine is the active ingredient in tobacco.
•
Nicotine stimulates one type of acetylcholine receptor known as the nicotinic receptor.
•
Nicotinic receptors are found in the central nervous system, the nerve-muscle junction of
skeletal muscles and in the nucleus accumbens.
•
Nicotinic receptors are also abundant in the nucleus accumbens and facilitate dopamine release.
•
Drugs and the Synapse
•
Opiate drugs are those that are derived from (or similar to those derived from) the opium
poppy.
•
Opiates decrease sensitivity to pain and increase relaxation by attaching to endorphin receptors
in the brain.
•
Examples: morphine, heroin, methadone.
•
Drugs and the Synapse
•
The brain produces peptides called endorphins.
•
Endorphin synapses may contribute to certain kinds of reinforcement by inhibiting the release of
GABA indirectly.
•
Inhibiting GABA indirectly releases dopamine.
•
Endorphins attach to the same receptors to which opiates attach.
•
Drugs and the Synapse
•
Tetrahydocannabinol (THC) is the active ingredient in marijuana.
•
THC attaches to cannabinoid receptors throughout the brain but especially the cerebral cortex,
cerebellum, basal ganglia, and hippocampus.
•
Anandamide and 2-AG are the endogenous chemicals that attach to these receptors.
•
The location of the receptors in the brain may account for the subjective effects of loss of time,
an intensification of sensory experience, and also memory impairment.
•
The cannabinoid receptors are located on the presynaptic neuron and inhibit the release of
glutamate and GABA.
•
Drugs and the Synapse
•
Hallucinogenic drugs cause distorted perception.
•
Many hallucinogenic drugs resemble serotonin in their molecular shape.
•
Hallucinogenic drugs stimulate serotonin type 2A receptors (5-HT2A) at inappropriate times or
for longer duration than usual thus causing their subjective effect.
•
Drugs and the Synapse
•
Alcohol is a drug that has a long historical use and is used widely throughout the world.
•
In moderate amounts, alcohol is associated with relaxation.
•
In greater amounts it impairs judgment and damages the liver and other organs.
•
Alcoholism/alcohol dependence is the continued use of alcohol despite medical or social harm
even after one has decided to quit or decrease drinking.
•
Drugs and the Synapse
•
Alcohol has a number of diverse physiological effects including:
–
Inhibition of sodium across the membrane.
–
Expansion of the surface of membranes.
–
Decreased serotonin activity.
–
Enhanced response by the GABAA receptor.
–
Blockage of glutamate receptors.
–
Increased dopamine activity.
•
Drugs and the Synapse
•
The genetic basis for early-onset alcoholism is stronger than for later-onset, especially in men.
•
Researchers distinguish between two types of alcoholism
–
Type I/Type A
–
Type II/Type B
•
Substance Abuse and Addictions
•
Type I/Type A characteristics include:
–
Later onset.
–
Gradual onset.
–
Fewer genetic relatives with alcoholism.
–
Equal quantity between men and women.
–
Less severe.
•
Substance Abuse and Addictions
•
Type II/Type B characteristic include:
•
–
Earlier onset (usually before 25).
–
More rapid onset.
–
More genetic relatives with alcoholism.
–
Men outnumber women.
–
Often severe.
–
Often associated with criminality.
Drugs and the Synapse
Various factors contribute to continued substance abuse:
•
Tolerance develops
•
Cravings in response to cues
•
Brain reorganization (nucleus accumbens and prefrontal cortex)
•
Drugs and the Synapse
•
Genes influence the likelihood of alcoholism in various ways:
–
Sensitivity of Dopamine type 4 receptor
–
Control of COMT enzyme that breaks down dopamine
•
Drugs and the Synapse
•
Medications used to combat alcoholism include:
–
Antabuse.
–
Methadone.
–
Many do not respond to other treatments so medications have been used to reduce
cravings.
•
Drugs and the Synapse
•
Antabuse (disulfiram) works by antagonizing the effects of acetaldehyde dehydrogenase.
•
After alcohol consumption, enzymes in the liver metabolize it into a poisonous substance called
acetaldehyde.
•
Acetaldehyde is converted by the enzyme acetaldehyde dehydrogenase into acetic acid, a
chemical that the body can use as a source of energy.
•
Accumulation of acetaldehyde results in sickness.
•
Drugs and the Synapse
•
Most studies suggest that Antabuse has been only moderately effective.
•
When effective, it supplements the alcoholic’s own commitment to quit.
•
Daily routine of pill ingestion may reaffirm commitment not to drink.
•
Many quit taking the pill and continue to drink.
•
Drugs and the Synapse
•
Methadone is an opiate similar to heroin and morphine but is absorbed and metabolized slowly.
•
Perceived to be less harmful than other drugs.
•
Assumed to satisfy the cravings associated with the previous drug use and allow the person to
carry on with their life.