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Team RITALIN: Research in Testing ADHD's Link to Impulsivity in Neuroscience 13 June 2013

Impact of prenatal nicotine exposure on impulsivity and neural activity in medial prefrontal cortex. Team RITALIN: Research in Testing ADHD's Link to Impulsivity in Neuroscience 13 June 2013. Introduction. Introduction. Prenatal Nicotine Exposure (PNE).

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Team RITALIN: Research in Testing ADHD's Link to Impulsivity in Neuroscience 13 June 2013

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  1. Impact of prenatal nicotine exposure on impulsivity and neural activity in medial prefrontal cortex Team RITALIN: Research in Testing ADHD's Link to Impulsivity in Neuroscience 13 June 2013

  2. Introduction Introduction Prenatal Nicotine Exposure (PNE) • PNE is linked to many psychiatric disorders • Women who smoke during pregnancy are three times as likely to have children diagnosed with ADHD • 1 in 5 women still smoke during pregnancy • Nicotine causes changes in the development that alters dopaminergic & noradrenergic pathways in the brain • Several studies show behavioral, neuroanatomical, & neurochemical disturbances after PNE • Benefits of methylphenidate, a common ADHD drug, point to PNE as a valuable animal model of impulsivity

  3. Introduction Attention Deficit Hyperactivity Disorder (ADHD) • Symptoms: impulsivity, hyperactivity, & inattention • Affects 5-10% of all school age children • Twentyfold increase in prescription of ADHD drugs in the past 30 years • Diagnoses based on qualitative observations • Limited research on the neurobiology of the disorder • ADHD drugs are addictive stimulants • Fetal nicotine rats and humans with ADHD have similar deficits on behavioral tasks for hyperactivity & impulsivity

  4. Introduction Modeling Impulsivity • Animal model validity • Face validity • Conduct validity • Predictive validity • What areas or circuits are involved? • How can we uncover more about the neurobiology?

  5. Introduction Medial Prefrontal Cortex (mPFC)

  6. Introduction Stop Signal Task (SST)

  7. Introduction Research Questions • Is there a correlation between neural firing in the mPFC cortex and impulsivity in control rats? • Is neural firing in the mPFC cortex disrupted and impulsivity increased in fetal nicotine rats? • Is there a correlation between this disrupted firing and increased impulsivity?

  8. Methodology Phase 1: Rat Breeding & Selection • Significant differences in water consumption & mother weights • No significant differences in pregnancy duration, pups per litter, pup birth weight, or locomotion* • Randomly selected 8 males each from 37 PNE pups (from 3 dams) and 39 control pups (from 3 dams)

  9. Methodology Phase 2: SST Training & Surgery • Compare movement times and percent correct on stop and go trials

  10. Results

  11. Results

  12. Results

  13. Results

  14. Results Post-Surgery Behavior

  15. Methodology Phase 3: Neural Recording & Analysis • 12 rats from the control and PNE groups performed 157 sessions, over which we collected neural firing from 346 cells

  16. Methodology

  17. Results Histograms for Above/Below Baseline Firing

  18. Results Histograms for Preferred/Nonpreferred Stop/Go Trials

  19. Results Distributions for Preferred/Nonpreferred for Go Direction

  20. legend: go ipsi - blue go contra - green stop ipsi - red stop contra - yellow Results Histograms for Contra/Ipsi Stop/Go Trials * legend: go ipsi - blue go contra - green stop ipsi - red stop contra - yellow

  21. Results Subtraction Plots for Preferred/Nonpreferred Stop/Go Trials

  22. Discussion Preliminary Conclusions • Behavior • PNE rats were more impulsive (as measured by SCRT) • However, they were better at basic task procedures (eg responding to spatial cue lights) • Neural recordings • Signals from neurons which encode stopping an already initiated movement were attenuated in PNE rats as compared to controls • Signals from neurons which encode direction towards the correct behavioral response were also attenuated as compared to controls • This points to a neurophysiological pathway disruption in inhibiting impulsivity caused by PNE

  23. Discussion Future Directions • For my team: • Finish collecting data for additional controls • Complete data analysis • Present data at Society for Neuroscience Conference • Write & present our thesis at the Senior Thesis Conference • For someone else: • Try a different task (or SST with different parameters) • Give nicotine postnatally • Administer ADHD drugs to PNE rats and controls

  24. My Team

  25. Questions? Questions?

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