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 the synapse • Discuss how the altered synapses may affect the adolescent brain • Play “Jeopardy Game” on neurobiology
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.
What does a synapse look like? Electron Micrograph Microscopy with Fluorescent Proteins Microscopy with Fluorescent Proteins Murthy_HHMI_teachers_2005_sub.ppt
Key to Previous Diagram • Impulse from action potential opens ion channels for Ca++ • The increased Ca++ concentration in the axon terminal initiates the release of the neurotransmitter (NT) • NT is released from its vesicle and crosses the “gap” or synaptic cleft and attaches to a protein receptor on the dendrite
Key to Diagram (cont.) • Interaction of NT and protein receptor open post-synaptic membrane ion channel for Na+ • After transmission the NT is either degraded by an enzyme or taken back into the pre-synaptic membrane by a transporter or reuptake pump
Synapse Animation To see an animation of a synapse, 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 a single type of neurotransmitter • The major neurotransmitters are indicated on the next slide.
Major Neurotransmitters in the Body NIH Publication No. 00-4871
Drugs Interfere with Neurotransmission • Drugs can affect synapses at a variety of sites and in a variety of ways, including: • Increasing number of impulses • Release NT from vesicles with or without impulses • Block reuptake or block receptors • Produce more or less NT • Prevent vesicles from releasing NT
Three Drugs (of many) which affect Neurotransmission Methamphetamine Nicotine Alcohol seattlepi.nwsource.com/ methamphetamines/ science.howstuffworks.com/ alcohol.htm
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 seattlepi.nwsource.com/ methamphetamines/ NIH Publication No. 00-4871
Result: More dopamine in the Synaptic Cleft • This causes neurons to fire more often than normal resulting in a euphoric feeling.
Problems…… • After the drug wears off, dopamine levels drop, and the user “crashes”. The euphoric feeling will not return until the user takes more methamphetamine • Long-term use of methamphetamine causes dopamine axons to wither and die. • Note that cocaine also blocks dopamine transporters, thus it works in a similar manner. • To see an animation on cocaine and brain synapses, click here.
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 the presynaptic neuron.
NIH Publication No. 00-4871 • 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.
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.
GABA and the GABA Receptor • GABA is a neurotransmitter that has an inhibitory effect on neurons. • When GABA attaches to its receptor on the postsynaptic membrane, it allows Cl- ions to pass into the neuron. • This hyperpolarizes the postsynaptic neuron to inhibit transmission of an impulse.
Alcohol and the GABA Receptor • When alcohol enters the brain, it binds to GABA receptors and amplifies the hyperpolarization 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 From AMA pub 9416 • 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.
The Adolescent Brain (cont.) • In addition, short-term or moderate drinking impairs learning and memory far more in youth than adults. • Adolescents need only drink half as much as adults to suffer the same negative effects. • To see an animation of GABA receptors and the influence of alcohol, click here.
Drugs That Influence Neurotransmitters NIH Publication No. 00-4871
Review - Jeopardy Game • Click here to play neurobiology jeopardy www.ibiblio.org/.../ greviews/jeop/jeop1.gif
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, Campbell and Reece, 6th Edition, Benjamin Cummings, San Francisco, 2002 Resources
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/HHMI Summer Camp for helping to make this a great experience. Special thanks to Tara Bennett, Susan Johnson, and my computer buddy, Katie Horne.