1. Dopamine: A Transmitter of Motion and Motivation Margaret E. Rice, Ph.D. Department of Neurosurgery Department of Physiology and Neuroscience Druckenmiller Celebration, 21 October 2009

2. Stock Whizzes Born Not Made, With Right Dopamine Gene By Rob Waters Oct. 2009 (Bloomberg) -- People who excel at making snap decisions and learn quickly from their mistakes, skills tied to successful stock traders, may share a genetic secret, according to a study by German neuroscientists. These talents have been linked in research to people who carry two copies of a gene variant, called VAL, that influences the actions of the brain chemical dopamine, according to scientists at the Max Planck Institute for Human Development in Berlin. Their report was published today in the Proceedings of the National Academy of Sciences. Stock Whizzes Born Not Made, With Right Dopamine Gene By Rob Waters Oct. 2009 (Bloomberg) -- People who excel at making snap decisions and learn quickly from their mistakes, skills tied to successful stock traders, may share a genetic secret, according to a study by German neuroscientists. These talents have been linked in research to people who carry two copies of a gene variant, called VAL, that influences the actions of the brain chemical dopamine, according to scientists at the Max Planck Institute for Human Development in Berlin. Their report was published today in the Proceedings of the National Academy of Sciences. PNAS October 20, 2009 vol. 106 no. 42 17951–17956 Stock Whizzes Born Not Made, With Right Dopamine Gene http://bit.ly/xTx SX $$ - alea http://bit.ly/xTx SX

3. Frontal cortex Cognition Working memory Schizophrenia Depression Striatum Motion Motor learning Parkinson’s Dystonia Tourette’s Substantia nigra - SNc Nucleus accumbens Motivation, reward Addiction (cocaine, amphetamine, nicotine, food, gambling) Midbrain Ventral tegmental area - VTA

4. Human midbrain Substantia nigra (SNc) Parkinson’s disease Pathophysiology Primary: loss of SNc DA neurons ControlParkinson’s Nigrostriatal dopamine pathway… SNc Striatum Michael J. FoxMuhammad Ali Pope John Paul II Janet RenoKatherine Hepburn

5. Why do dopamine neurons die in Parkinson’s disease? Genetic? Toxin/pesticide exposure? Oxidative stress? Mitochondrial dysfunction? Rotenone Powerhouse of cells

6. Tying these together: Hydrogen peroxide ( H 2 O 2, an oxidant) is a surprising inhibitor of nigrostriatal DA neurons and DA release Produced in nigral DA neurons Generated from oxygen metabolism in mitochondria Uncontrolled peroxide production with rotenone exposure Future goals: Identify therapeutic targets in Parkinson’s Inhibit peroxide generation Amplify peroxide breakdown Examine peroxide regulation in genetic models of PD