Transcript Document

Chapter 3
Synapses
The Concept of the Synapse
• Synapse: gap between
one neuron’s
presynaptic terminal and
another receiving neuron
• Discovered by Santiago
Ramon y Cajal in the
late 1800s
The Concept of the Synapse
• In 1906, Charles Scott
Sherrington:
– coined the term
synapse and proposed
that neurons
communicate by
transmitting chemicals
at synapses
– conducted research on
synaptic communication
by studying reflexes
(automatic muscular
responses to stimuli).
Reflex arc: the complete circuit from
sensory neuron to muscle response
Fig. 3-1, p. 52
Sherrington deduced three properties of reflexes:
1. Reflexes are slower than conduction along a
single axon.
Sherrington deduced three properties of reflexes:
2. Several weak stimuli presented at slightly
different times or slightly different locations
produces a stronger reflex than a single stimulus
does.
Sherrington deduced three properties of reflexes:
3. As one set of muscles relaxes, another set
becomes excited.
John Eccles (1964)
• Postsynaptic neuron: receives the message
• Presynaptic neuron: delivers the synaptic potential
• Spatial summation: synaptic input from several locations
can have a cumulative effect and trigger a nerve impulse
• Temporal summation: repeated stimuli can have a
cumulative effect and can produce a nerve impulse when a
single stimuli is too weak.
Fig. 3-4, p. 54
Graded potentials
• either depolarize (excite) or hyperpolarize
(inhibit) the postsynaptic neuron
• decay over time and space
The Concept of the Synapse
• Excitatory postsynaptic
potential (EPSP) depolarizes
neuron’s membrane
– is a graded (excitatory)
potential that decays over
time and space.
– The cumulative effect of
EPSPs are the basis for
temporal and spatial
summation.
• Inhibitory postsynaptic potential
(IPSP): hyperpolarizes
membrane.
– Serves as an active “brake”,
that suppresses excitation.
The Concept of the Synapse
• The spontaneous firing rate refers to the
periodic production of action potentials
despite synaptic input.
• EPSPs increase the nerve cell’s spontaneous
firing rate.
• IPSPs decrease the nerve cell’s spontaneous
firing rate.
Chemical Events at the Synapse
• Otto Loewi (1920): Discovered that
transmission of a message across the
synapse occurs by chemical means.
Neuroanatomy Handout #2: The Synapse
and Neurotransmitters
•
•
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Synaptic cleft (E)
Axon membrane (A)
Presynaptic membrane (A1)
Synaptic vesicles (B): tiny
spherical packets located in
the presynaptic terminal where
neurotransmitters are held for
release
• Neurotransmitters (C):
chemicals that travel across
the synapse and allow
communication between
neurons
• Neurotransmitter fragments
(C1)
Neurotransmitters
• Approx. 100 different kinds
• Neurons synthesize neurotransmitters and other chemicals
from substances provided by the diet.
– Acetylcholine is synthesized from choline found in milk,
eggs, and nuts.
– Serotonin is synthesized from tryptophan found in turkey
and soy.
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Major sequence of events for neurotransmitters:
1. The neuron
synthesizes
chemicals that serve
as
neurotransmitters.
2. Neurons store
neurotransmitters in
axon terminals or
transport them there
(transportation from
cell body can take
hours or days).
3. An action potential
triggers the release
of neurotransmitters
into the synaptic
cleft.
Major sequence of events for neurotransmitters:
• Exocytosis (D) refers
to the excretion of
the neurotransmitter
from the presynaptic
terminal into the
synaptic cleft.
– Triggered by an
action potential
arriving from the
axon.
Major sequence of events for neurotransmitters:
4. The neurotransmitters
travel across the cleft
and attach to the
postsynaptic
membrane (F) at the
postsynaptic receptor
sites (G).
5. The neurotransmitters
separate from the
receptors.
6. The neurotransmitters
are taken back into the
presynaptic neuron,
diffuse away, or are
inactivated by
chemicals.
Major sequence of events for neurotransmitters:
• Reuptake (endocytosis)
(H) refers to the
presynaptic neuron
taking up most of the
neurotransmitter
molecules intact and
reusing them.
Chemical Events at the Synapse
• 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.
Pituitary Gland
•
Attached to the
hypothalamus and
consisting of two distinct
glands that each release a
different set of hormones:
– Anterior pituitarycomposed of glandular
tissue and synthesizes
six hormones.
– Posterior pituitarycomposed of neural
tissue and can be
considered an
extension of the
hypothalamus
Drugs and the Synapse
•
Drugs work by doing one or more of the
following to neurotransmitters:
1. Increasing the synthesis.
2. Causing vesicles to leak.
3. Increasing release.
4. Decreasing reuptake.
5. Blocking the breakdown into inactive
chemical.
6. Directly stimulating or blocking
postsynaptic receptors.
Table 3-3, p. 76
Link to Mouse Party
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
• 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.
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
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
• Amphetamines stimulate dopamine synapses
by increasing 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
• MDMA (Ecstasy):
– increases the release of dopamine at low
doses that account for its stimulant properties
– 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:
– active ingredient in tobacco
– stimulates an acetylcholine receptor known as
the nicotinic receptor, found in
• central nervous system
• nerve-muscle junction of skeletal muscles
• nucleus accumbens
Drugs and the Synapse
• Opiate drugs:
– derived from opium poppy
– decrease sensitivity to pain and increase
relaxation
• Examples: morphine, heroin, methadone.
Drugs and the Synapse
• Endorphins:
– naturally produced neurotransmitters
– ease pain
– inhibit GABA, allowing dopamine to exert its
effect
– attach to the same receptors to which
opiates attach.
Drugs and the
Synapse
• Tetrahydocannabinol (THC):
– active ingredient in marijuana
– attaches to cannabinoid receptors, especially in
the cerebral cortex, cerebellum, basal ganglia,
and hippocampus.
• Cannabinoids: chemicals related to THC, typically
used medically
• Anandamide and 2-AG are the endogenous
chemicals that attach to these receptors.
Drugs and the Synapse
• Hallucinogenic drugs:
– cause distorted perception
– may resemble serotonin in their molecular shape
– stimulate serotonin type 2A receptors (5-HT2A) at
inappropriate times or for longer duration than
usual thus causing their subjective effect.
Alcohol and Alcoholism
• Alcohol:
– is associated with relaxation
– in greater amounts impairs judgment and
damages the liver and other organs
– dependence (alcoholism) is the habitual
use of alcohol despite medical or social
harm
Alcohol and Alcoholism
• Alcohol has a number of diverse physiological
effects, including:
– Enhanced response by the GABAA
receptor
– Blockage of glutamate receptors
– Increased dopamine activity
Alcohol and Alcoholism
• Strong influence of genetics on alcoholism
– 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
Alcohol and Alcoholism
• Type I/Type A characteristics include:
– Later onset (usually after 25)
– Gradual onset
– Fewer genetic relatives with alcoholism
– Equal quantity between men and women
Alcohol and Alcoholism
• Type II/Type B characteristics include:
– Earlier onset (usually before 25)
– More rapid onset
– More genetic relatives with alcoholism
– Men outnumber women
Alcohol and Alcoholism
• Genes influence the likelihood of alcoholism
in many ways, such as:
– being more sensitive and needing more
alcohol to provide reinforcement
– being linked with impulsivity
– influencing responses to stress and
anxiety-inducing experiences
– likelihood of prenatal exposure to alcohol
Alcohol and Alcoholism
• Research on sons of alcoholic fathers shows:
– Less average intoxication after one drink
– Stress decreases more than for the
average person
– Smaller than normal amygdala
Addiction
• Various factors contribute to continued
substance abuse:
– Tolerance: The body’s decrease in response
to a drug with repeated use
– Withdrawal: Uncomfortable/painful
symptoms once drug use is discontinued
– Cravings develop in response to cues
– Brain reorganization (nucleus accumbens
and prefrontal cortex)
Medications to Combat Alcohol Abuse
• Revia (naloxone) blocks opiate receptors,
thereby decreasing the pleasure from alcohol.
• Antabuse (disulfiram) works by making user
sick
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Medications to Combat Alcohol Abuse
• 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
Medications to Combat Opiate Abuse
• 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 cravings associated with
previous drug use
• Levomethadyl acetate (LAAM) is similar to
morphine but can be taken three times a week
rather than daily