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TRANSCRIPT
Synapses and Drugs
Raymond S. Broadhead
Brooks School
MCB/HHMI Summer Camp
July, 2005
Objectives
• Review the Synapse
• Discuss some drugs and their effects on thesynapse
• Discuss how the altered synapses mayaffect the adolescent brain
• Play “Jeopardy Game” on neurobiology
Review the Synapse
• What is a synapse?
• A synapse is the “gap” between the axon ofone nerve and the dendrite of the next one.
• The average neuron has 1,000 synapseswith other neurons.
What does a synapse look like?
Electron Micrograph
Microscopy withFluorescent ProteinsMicroscopy with
Fluorescent Proteins
Murthy_HHMI_teachers_2005_sub.ppt
Figure 48.12 A chemical synapse
Key to Previous Diagram
1. Impulse from action potential opens ionchannels for Ca++
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” or synaptic cleft and attaches to a proteinreceptor on the dendrite
Key to Diagram (cont.)
4. Interaction of NT and protein receptoropen post-synaptic membrane ionchannel for Na+
5. After transmission the NT is eitherdegraded by an enzyme or taken back intothe pre-synaptic membrane by atransporter or reuptake pump
Synapse Animation
To see an animation of asynapse, click here.
Copyright - Pearson Education
Neurotransmitters
• There are dozens of different neurotransmitters(NT) in the neurons of the body.
• NTs can be either excitatory or inhibitory
• Each neuron generally synthesizes and releases asingle type of neurotransmitter
• The major neurotransmitters are indicated onthe next slide.
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 painpathways.
Serotonin
Norepinephrine acts as a neurotransmitter and a hormone. In theperipheral 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 probablyalways 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 bythe brain reward system. Dopamine has multiple functions depending onwhere in the brain it acts. It is usually inhibitory.
Dopamine
A neurotransmitter used by the spinal cord neurons to control muscles andby many neurons in the brain to regulate memory. In most instances,acetylcholine is excitatory.
Acetylcholine
Role in the BodyNeurotransmitter
NIH Publication No. 00-4871
Drugs Interfere withNeurotransmission
• Drugs can affect synapses at a variety ofsites and in a variety of ways, including:
1. Increasing number of impulses2. Release NT from vesicles with or without
impulses3. Block reuptake or block receptors4. Produce more or less NT5. Prevent vesicles from releasing NT
Three Drugs (of many) whichaffect Neurotransmission
Methamphetamine
Nicotine
Alcohol
seattlepi.nwsource.com/ methamphetamines/
science.howstuffworks.com/ alcohol.htm
Methamphetamine alters Dopamine transmissionin 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/
Result: More dopamine in theSynaptic Cleft
• This causes neurons to fire more often thannormal resulting in a euphoric feeling.
Problems……1. After the drug wears off, dopamine levels drop,
and the user “crashes”. The euphoric feeling willnot return until the user takes moremethamphetamine
2. Long-term use of methamphetamine causesdopamine axons to wither and die.
3. Note that cocaine also blocks dopaminetransporters, thus it works in a similar manner.
4. To see an animation on cocaine and brainsynapses, click here.
What about Nicotine?
• Similar to methamphetamine and cocaine,nicotine increases dopamine release in asynapse.
• However, the mechanism is slightlydifferent.
• Nicotine binds to receptors on thepresynaptic neuron.
•Nicotine binds to the presynapticreceptors exciting the neuron to fire moreaction potentials causing an increase indopamine release.
•Nicotine also affects neurons byincreasing the number of synapticvesicles released.
NIH Publication No. 00-4871
How does alcohol affect synapses?
• Alcohol has multiple effects on neurons. Italters neuron membranes, ion channels,enzymes, and receptors.
• It binds directly to receptors foracetylcholine, serotonin, and gammaaminobutyric acid (GABA), and glutamate.
• We will focus on GABA and its receptor.
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.
Alcohol and the GABA Receptor
• When alcohol enters the brain, it binds toGABA receptors and amplifies thehyperpolarization effect of GABA.
• The neuron activity is further diminished
• This accounts for some
of the sedative affects
of alcohol
science.howstuffworks.com/ alcohol.htm
The Adolescent Brain and Alcohol
• The brain goes through dynamic change duringadolescence, and alcohol can seriously damagelong- and short-term growth processes.
• Frontal lobe development and the refinement ofpathways and connections continue until age 16,and a high rate of energy is used as the brainmatures until age 20.
• Damage from alcohol at this time can be long-term and irreversible.
From AMA pub 9416
The Adolescent Brain (cont.)
• In addition, short-term or moderatedrinking impairs learning and memoryfar more in youth than adults.
• Adolescents need only drink half as muchas adults to suffer the same negativeeffects.
• To see an animation of GABA receptorsand the influence of alcohol, click here.
Drugs That Influence Neurotransmitters
LSD
caffeine
no change in the amount ofneurotransmitter released, or
neurotransmitter cannot bind toits receptor on postsynaptic
neuron
block receptor with anothermolecule
No drug exampleless neurotransmitter releasedprevent vesicles from releasingneurotransmitter
probably does not work this wayless neurotransmitter in synapticcleft
produce less neurotransmitter
cocaine
amphetamine
more neurotransmitter present insynaptic cleft
block reuptake
nicotineincreased neurotransmitterrelease
release more neurotransmitter inresponse to an impulse
amphetamines
methamphetamines
increased neurotransmitterrelease
release neurotransmitter fromvesicles with or without impulses
nicotine, alcohol, opiatesincreased neurotransmitterrelease
increase the number of impulses
Drug that acts this wayEffect on Neurotransmitterrelease or availability
Change in Neurotransmission
NIH Publication No. 00-4871
Review - Jeopardy Game
• Click here to play neurobiology jeopardy
www.ibiblio.org/.../ greviews/jeop/jeop1.gif
Resources
• http://www.pbs.org/wnet/closetohome/home.html
• http://www.biologymad.com/NervousSystem/synapses.htm#drugs
• http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Synapses.html
• http://science.education.nih.gov/Customers.nsf/HSBrain?OpenForm
• Biology, Campbelland Reece, 6th Edition,Benjamin Cummings,San Francisco, 2002
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/
Acknowledgements
Thank you to all members of the MCB/HHMISummer Camp for helping to make this agreat experience. Special thanks to Tara
Bennett, Susan Johnson, and my computer
buddy, Katie Horne.