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

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

IntroductionIntroduction

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

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

Medial Prefrontal Cortex (mPFC)

Introduction

Stop Signal Task (SST)

Introduction

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

Phase 1: Rat Breeding & Selection

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)

Phase 2: SST Training & Surgery

Methodology

Compare movement times and percent correct on stop and go trials

Results

Results

Results

Results

Results

Post-Surgery Behavior

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

Methodology

ResultsHistograms for Above/Below Baseline Firing

ResultsHistograms for Preferred/Nonpreferred Stop/Go Trials

ResultsDistributions for Preferred/Nonpreferred for Go Direction

Results

legend:go ipsi - bluego contra - greenstop ipsi - redstop contra - yellow

legend:go ipsi - bluego contra - greenstop ipsi - redstop contra - yellow

Histograms for Contra/Ipsi Stop/Go Trials

*

ResultsSubtraction Plots for Preferred/Nonpreferred Stop/Go Trials

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

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

My Team

Questions?Questions?