Team RITALIN:

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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
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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

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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

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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?

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Introduction
Medial Prefrontal Cortex (mPFC)
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Introduction
Stop Signal Task (SST)
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Introduction
Research Questions

1. Is there a correlation between neural firing in
   the mPFC cortex and impulsivity in control rats?
2. Is neural firing in the mPFC cortex disrupted and
   impulsivity increased in fetal nicotine rats?
3. Is there a correlation between this disrupted
   firing and increased impulsivity?

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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)

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Methodology
Phase 2 SST Training Surgery

• Compare movement times and percent correct on
  stop and go trials

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Results
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Results
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Results
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Results
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Results
Post-Surgery Behavior
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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

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Methodology
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Results
Histograms for Above/Below Baseline Firing
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Results
Histograms for Preferred/Nonpreferred Stop/Go
Trials
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Results
Distributions for Preferred/Nonpreferred for Go
Direction
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Results
legend go ipsi - blue go contra - green stop
ipsi - red stop contra - yellow
Histograms for Contra/Ipsi Stop/Go Trials

legend go ipsi - blue go contra - green stop
ipsi - red stop contra - yellow
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Results
Subtraction Plots for Preferred/Nonpreferred
Stop/Go Trials
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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

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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

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My Team
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Questions?
Questions?