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

ALL COURSE INFO AT THERE IS NO D2L http://dosequis.colorado.edu/Courses/BrainWeb/ THERE IS NO D2L

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

Class Organization ALL course information is available from the course website Please bring a laptop to class everyday http://dosequis.colorado.edu/Courses/BrainWeb/ 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

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

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

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

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

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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.

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.

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

QUESTIONS?

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

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

Synaptic Anatomy

Different neurons are structurally different B 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

The Synapse Electrical Chemical

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

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.

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.

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

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

Ligand-gated vs. G-protein coupled receptors

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).

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

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