1. The Brain: Dysfunction to Disease MCDB 3651 A120 T+R 12:30-13:45
Michael Stowell
Office Porter B231
Amyotrophic lateral sclerosis Myasthenia gravis Bipolar disorder Autism Asperger’s Downs syndrome Cerebral palsy Charcot-Marie-Tooth Alzheimer’s FTD Parkinson's Huntington's Multiple sclerosis Creutzfeldt-Jakob Disease Lyme disease

2. ALL COURSE INFO AT THERE IS NO D2L
THERE IS NO D2L

3. Introductions What is your preferred name? What is your major?
What year are you?
Previous neuroscience courses?
What is your interest in this course?

4. Class Organization
ALL course information is available from the course website
Please bring a laptop to class everyday
Your grade (300 pts) will be based upon
In class and group participation using workshops and clickers (50 pts). Everyday 2 pts per day
Pre-class assignments and quizzes (100 pts).
Due every T and R before class by 12 AM.
Group Project Presentation (75 pts).
Creative scientific project for class presentation
Individually Written Paper (75 pts).
Review article style

5. Class Participation 50 pts
Clicker based (default code AA)
Base point for participation
Bonus point for correct response or peer driven correct response
Daily Workshops

6. The typical number of synapses in a human brain is
109 i.e. a billion
1012 i.e. a trillion
1014 i.e. a hundred trillion
1024 i.e. the number of stars in the universe
The typical number of synapses in a human brain is
109 i.e. a billion
1012 i.e. a trillion
1014 i.e. a hundred trillion
1024 i.e. the number of stars in the universe

7. MCDB3651: Brain, Dysfunction to Disease
DAILY WORKSHOPS Date_____________
Group Name_________________________
Members Present______________________________________________________________

8. Assignments and Quizzes 100 pts
Based upon assigned reading material
Must be completed before 12:00 noon the day of class
No make ups
Located at the b.socrative.com website
Link on class website

9. b.socrative.com/login/student

10. Please Enter Last Name and First Initial ONLY!

11. Click to Answer

12. Selected Answer Highlights

13. No Active Quiz

14. Groups and Group Project
You must establish working groups of 3-4 people. This will be the group you work with in class so please sit together. Groups must be established by end of class next Thursday, please feel free to move around before then.

15. Group Project 75 pts Scientifically based presentation to the class
35 min total
Explore in more depth a topic that you find intriguing.
Evaluate experimental data produced by scientists in this field.
Integrate experimental findings into your current knowledge base.
Draw conclusions and make inferences from what you have read on these topics.
Reflect on the many concepts you have learned.
Create something understandable to non-scientists.

16. Individual Paper 75 pts Based upon your group project
Written in a review style format
5 to 10 pages
Due one week following your group presentation

17. QUESTIONS?

18. ~1011 neurons ~1014 circuits/transistors ~1017 proteins
Make an X3 box One chips every day until about 20

19. Synaptic Transmission : a historical perspective
1. Golgi and Ramon Cajal (1900s) Histology neuronal connection via “Synapse” 2. Otto Loewi (1930s) Chemical transmission 3. Hodgkin and Huxley (1950s) Electrical model of transmission (giant squid) 4. Neher and Sakmann (1970s) Patch clamp for single ion channel recording 5. Doyle and McKinnon (1990s) Structure of K channel 6. Rothman, Schekman, Südhof (2000s) Vesicle trafficking

20. Synaptic Anatomy

21. Different neurons are structurally differentB C D E
Which of the neurons receives the most input? A B C D E
Which of the neurons receives the most input? A B C D E

22. The Synapse
Electrical
Chemical

23. Electrical Synapse
Membranes of the pre- and post-synaptic neurons come close together with gap junctions that allow passage of ions.
Are less common than chemical synapses
Correspond to gap junctions found in other cell types
Are important in the CNS in:
Awakening
Mental attention
Emotions and memory
Ion and water homeostasis

24. Chemical Synapse
Almost all synapses used for signal transmission in the CNS of humans are chemical synapses.
Four classes of neurotransmitter
1. Amino acids: glutamate, aspartate, D-Ser, γ-aminobutyric acid (GABA), glycine.
2. Monoamines and other biogenic amines: dopamine (DA), norepinephrine (noradrenaline; NE, NA), epinephrine (adrenaline), histamine, serotonin (SE, 5-HT)
3. Peptides: somatostatin, substance P, opioid peptides
4. Others: acetylcholine (ACh), adenosine, anandamide, nitric oxide, etc.
They are stored in “synaptic vesicles”: acidic interior (pH = 5.5), maintained by a vacuolar-type, proton-translocating ATPase driven by H+ pump and specific transmitter transporter.

25. Criteria for chemical transmission
1. Synthesis of the neurotransmitter in the presynaptic nerve terminals 2. Storage of the neurotransmitter in secretory vesicles. 3. Regulated release of neurotransmitter in the synaptic space between the pre- and post-synaptic neurons. 4. Presence of receptors on the postsynaptic membrane mimics the effect of nerve stimulation 5. A means for “termination” of the action of the released neurotransmitter.

26. Many different kinds of neurotransmitters and receptors(many act at both ionotropic and metabotropic receptors): Acetylcholine (Ach) Glutamate GABA Glycine Serotonin Catecholamines: Dopamine, Epinephrine, Norepinephrine Purinergic: ATP and adenosine Small molecules: Nitric Oxide (NO) Neuropeptides: opiods

27. Cell-surface receptors utilize four distinct molecular mechanisms for transmembrane signaling
Guanyl cyclase (peptide) receptors, also soluble guanylat cyclase NO receptor, tyrosine kinase like ras, vegf etc, GPCR

28. Ligand-gated vs. G-protein coupled receptors

29. Ionotropic Metabotropic NT receptor directly affects an ion channel
If channel is opened, an electrical current is generated, creating a change in the potential of the membrane:
Metabotropic
Many possible “downstream” consequences
NT receptor is a G-protein coupled receptor.
Binding triggers a second messenger cascade that alters the post-synaptic cell
The effect can be long lasting (e.g. change gene expression, phosphorylation of an ion channel).

30. Takamori et al. Cell 127 (2006)
Group problem. Pick 1 or 2 molecules and discuss why they are important for synaptic vesicles.
Team Workshop 1: Choose 2 molecules present in a synaptic vesicle and explain:
1. What it does
2. Why it is important for the function of a synaptic vesicle

31. Remember Before 12 noon of the next class day:
go to b.socrative.com/student/login and complete the quiz