synapses and drugs[1]
TRANSCRIPT
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Synapses and Drugs
Raymond S. Broadhead
Brooks School
MCB/HHMI Summer Camp
July, 2005
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Objectives
Review the Synapse
Discuss some drugs and theireffects on thesynapse
Discuss how the altered synapses may
affect the adolescent brain
Play Jeopardy Game on neurobiology
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Review the Synapse
What is a synapse?
A synapse is the gap between the axon of
one nerve and the dendrite of the next one.
The average neuron has 1,000 synapses
with other neurons.
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What does a synapse look like?
Electron Micrograph
Microscopy with
Fluorescent ProteinsMicroscopy with
Fluorescent Proteins
Murthy_HHMI_teachers_2005_sub.ppt
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Figure 48.12 A chemical synapse
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Key to Previous Diagram1. Impulse from action potential opens ion
channels forCa++
2. The increased Ca++ concentration in the axonterminal initiates the release of theneurotransmitter (NT)
3. NT is released from its vesicle and crosses the
gap orsynaptic cleft and attaches to a proteinreceptor on the dendrite
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Key to Diagram (cont.)
4. Interaction ofNT and protein receptoropen post-synaptic membrane ion
channel forNa+
5. After transmission the NT is eitherdegraded by an enzyme or taken back intothe pre-synaptic membrane by atransporter orreuptake pump
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Synapse Animation
To see an animation of a
synapse, clickhere.
Copyright - Pearson Education
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Neurotransmitters
There are dozens of different neurotransmitters
(NT) in the neurons of the body.
NTs can be eitherexcitatory orinhibitory
Each neuron generally synthesizes and releases a
single type of neurotransmitter
The major neurotransmitters are indicated on
the next slide.
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Major Neurotransmitters in the Body
A neurotransmitter involved in many functions including mood, appetite,
and sensory perception. In the spinal cord, serotonin is inhibitory in pain
pathways.
Serotonin
Norepinephrine acts as a neurotransmitter and a hormone. In the
peripheral nervous system, it is part of the flight-or-flight response. In thebrain, it acts as a neurotransmitter regulating normal brain processes.
Norepinephrine is usually excitatory, but is inhibitory in a few brain areas.
Norepinephrine
A neurotransmitter used mainly by neurons in the spinal cord. It probably
always acts as an inhibitory neurotransmitter.
Glycine
The most common excitatory neurotransmitter in the brain.Glutamate
The major inhibitory neurotransmitter in the brain.GABA
(gamma-aminobutyric acid)
The neurotransmitter that produces feelings of pleasure when released by
the brain reward system. Dopamine has multiple functions depending on
where in the brain it acts. It is usually inhibitory.
Dopamine
A neurotransmitter used by the spinal cord neurons to control muscles and
by many neurons in the brain to regulate memory. In most instances,
acetylcholine is excitatory.
Acetylcholine
Role in the BodyNeurotransmitter
NIH Publication No. 00-4871
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Drugs Interfere with
Neurotransmission
Drugs can affect synapses at a variety ofsites and in a variety of ways, including:
1. Increasing number of impulses
2. Release NT from vesicles with or without
impulses
3. Block reuptake or block receptors
4. Produce more or less NT
5. Prevent vesicles from releasing NT
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Three Drugs (of many) which
affect Neurotransmission
Methamphetamine
Nicotine
Alcohol
seattlepi.nwsource.com/ methamphetamines/
science.howstuffworks.com/ alcohol.htm
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Methamphetamine alters Dopamine transmission
in two ways:
1. Enters dopamine vesicles in axon terminal causing
release of NT
2. Blocks dopamine transporters from pumping dopamine
back into the transmitting neuron
NIH Publication No. 00-4871
seattlepi.nwsource.com/ methamphetamines/
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Result: More dopamine in the
Synaptic Cleft
This causes neurons to fire more often than
normal resulting in a euphoric feeling.
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Problems1. After the drug wears off, dopamine levels drop,
and the user crashes. The euphoric feeling will
not return until the user takes more
methamphetamine2. Long-term use of methamphetamine causes
dopamine axons to wither and die.
3. Note that cocaine also blocks dopamine
transporters, thus it works in a similar manner.
4. To see an animation on cocaine and brain
synapses, clickhere.
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What about Nicotine?
Similar to methamphetamine and cocaine,
nicotine increases dopamine release in a
synapse.
However, the mechanism is slightly
different.
Nicotine binds to receptors on thepresynaptic neuron.
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Nicotine binds to the presynaptic
receptors exciting the neuron to fire more
action potentials causing an increase in
dopamine release.Nicotine also affects neurons by
increasing the number of synaptic
vesicles released.
NIH Publication No. 00-4871
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How does alcohol affect synapses?
Alcohol has multiple effects on neurons. It
alters neuron membranes, ion channels,
enzymes, and receptors.
It binds directly to receptors for
acetylcholine, serotonin, and gamma
aminobutyric acid (GABA), and glutamate. We will focus on GABA and its receptor.
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GABA and the GABA Receptor
GABA is a neurotransmitter that has aninhibitory effect on neurons.
When GABA attaches to its receptor on thepostsynaptic membrane, it allows Cl- ionsto pass into the neuron.
This hyperpolarizes the postsynapticneuron to inhibit transmission of animpulse.
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Alcohol and the GABA Receptor
When alcohol enters the brain, it binds to
GABA receptors and amplifies the
hyperpolarization effect ofGABA.
The neuron activity is further diminished
This accounts for some
of the sedative affects
of alcohol
science.howstuffworks.com/ alcohol.htm
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The Adolescent Brain and Alcohol
The brain goes through dynamic change during
adolescence, and alcohol can seriously damage
long- and short-term growth processes. Frontal lobe development and the refinement of
pathways and connections continue until age 16,
and a high rate of energy is used as the brain
matures until age 20. Damage from alcohol at this time can be long-
term and irreversible.
From AMA pub 9416
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The Adolescent Brain (cont.)
In addition, short-term or moderatedrinking impairs learning and memory
far more in youth than adults. Adolescents need only drink half as much
as adults to suffer the same negativeeffects.
To see an animation of GABA receptorsand the influence of alcohol, clickhere.
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Drugs That Influence Neurotransmitters
LSD
caffeine
no change in the amount of
neurotransmitter released, or
neurotransmitter cannot bind to
its receptor on postsynaptic
neuron
block receptor with another
molecule
No drug exampleless neurotransmitter releasedprevent vesicles from releasingneurotransmitter
probably does not work this wayless neurotransmitter in synaptic
cleft
produce less neurotransmitter
cocaine
amphetamine
more neurotransmitter present in
synaptic cleft
block reuptake
nicotineincreased neurotransmitter
release
release more neurotransmitter in
response to an impulse
amphetamines
methamphetamines
increased neurotransmitter
release
release neurotransmitter from
vesicles with or without impulses
nicotine, alcohol, opiatesincreased neurotransmitter
release
increase the number of impulses
Drug that acts this wayEffect on Neurotransmitter
release or availability
Change in Neurotransmission
NIH Publication No. 00-4871
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Review - Jeopardy Game
Clickhere to play neurobiology jeopardy
www.ibiblio.org/.../ greviews/jeop/jeop1.gif
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Resources http://www.pbs.org/w
net/closetohome/home
.html http://www.biologyma
d.com/NervousSystem/synapses.htm#drugs
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Synapses.html
http://science.educatio
n.nih.gov/Customers.n
sf/HSBrain?OpenForm
Biology, Campbell
and Reece, 6th Edition,
Benjamin Cummings,San Francisco, 2002
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More Related Websites to Explore http://faculty.washington.edu/chudler/neurok.html
http://www.teachersdomain.org/
http://science.nhmccd.edu/biol/ap1int.htm http://www.hhmi.org/
http://www.med.harvard.edu/AANLIB/home.html
http://www.med.harvard.edu/publications/On_The
_Brain/
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Acknowledgements
Thank you to all members of the MCB/HHMI
Summer Camp for helping to make this a
great experience. Special thanks to Tara
Bennett, Susan Johnson, and my computer
buddy, Katie Horne.