1. 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

2. 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 Introduction

3. 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 Introduction

4. 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? Introduction

5. Medial Prefrontal Cortex (mPFC) Introduction

6. Stop Signal Task (SST) Introduction

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

10. Phase 1: Rat Breeding & Selection Acclimate dams to nicotine in water Breed rats Compare populations Select pups Methodology 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)

11. Phase 2: SST Training & Surgery Task training Between group differences observed Implant electrodes Methodology Compare movement times and percent correct on stop and go trials

12. Results

16. Post-Surgery Behavior

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

18. Methodology

19. Results Histograms for Above/Below Baseline Firing

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

21. Results Distributions for Preferred/Nonpreferred for Go Direction

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

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

24. Preliminary Conclusions Discussion 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

25. 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 Discussion

26. My Team

27. Questions?