CURF Poster

1
Acknowledgements: College Alumni Society Attention and Motivation in Female Offspring of Maternal Malnutrition J.R. Lidsky-Everson, N. Grissom, and T. M. Reyes University of Pennsylvania, Perelman School of Medicine, Philadelphia PA Previous data suggests that the maternal diet and gestational size of male mice greatly affects their attention and motivation. Using a 5-choice serial reaction time task to model attention, male mice born large for gestational age tended to have problems with impulse control while male mice born small for gestational age tended to be more inattentive. Because ADHD is more commonly diagnosed in males, we were interested in whether females exhibited similar deficits or if they were spared from these deficits. Maternal high fat and maternal low protein diets during gestation were used to model SGA and LGA. The 5-choice serial reaction time test was replicated with the female offspring. The results indicated that female mice characterized for reward, attention and impulse control function showed similar patterns of deficits to those of the male mice. This suggests that the attention and motivational deficits exhibited under maternal high fat and low protein diets are independent of sex differences. METHODS Progressive Ratio FR1 ABSTRACT The mice were put through three operant behavior tasks. These tasks were conducted in a chamber that indicated a cue through illuminated holes in the back and dispensed yoohoo as a reward for appropriate responses. The chambers were equipped with 9 holes which were illuminated in accordance with the specific task being tested. Responses were recorded when nose pokes broke the infrared beams at the back of the chamber. In the progressive ratio test, the animals were cued by a light in the back of the chamber at the center hole. However, in order to receive yoohoo, the mice had to break the infrared beam of the hole by registering nose pokes. At first the mice only had to nose poke once in order to receive the reward. After this was completed correctly three times, the mice were expected to respond progressively more times before they were rewarded. Five-Choice Serial Reaction Time Test Incorr ect Prematu re Omissi on Corre ct During the 5- choice task, one of the five holes in the back of the chamber lit up after an intertrial interval. The mice had limited time to respond through a nose poke to the illuminated hole. If the trial was completed successfully (the mouse nose poked the correct hole), yoohoo was dispensed. The 5- choice test included five separate schedules The task measured attention by gathering both correct responses and incorrect responses. Error trials could be obtained through omission and commission. Omission was recorded when the mouse did not respond. Commission was recorded when either the mouse responded early or responded incorrectly. Back of chamber FR1 and Progressive Ratio FR1 Trial number 1 2 3 4 5 6 7 8 9 10 11 12 …n Ratio for reward 1 1 1 2 2 2 4 4 4 7 7 7 …n Progressive Ratio 5-Choice The progressive ratio test examined how hard the mice were willing to work for a reward and measured motivational deficits. At some point the mice abandoned the task. The number of trials completed is an index of motivation for each mouse. Male Progressive Ratio Test Previously, the male LGA mice stopped this task the earliest indicating a decreased motivation to work for the reward. Female Progressive Ratio Test Females born large for gestational age exhibited similar behavior of decreased motivation. Summary and Discussion The 5-choice serial reaction time test measured attention and motivation by gathering both correct and incorrect responses. Omitted responses were an indication of inattention while incorrect and premature responses were an indication of impulsivity. Male 5-choice serial reaction time test Previously, male SGA mice tended to have higher rates of omitted trials which reflect inattention whereas LGA mice tended to have higher instances of incorrect responses and premature responses , which reflect impulsivity. Female 5-choice serial reaction time test COL 2015 Female offspring born small for gestational age made a significant amount of omission errors indicating inattention deficits. The offspring born large for gestational age showed a strong trend exclusively toward registering incorrect responses. Neither group showed signs of making excessively more premature responses than the control group. Male FR1 to any hole Previously, male HF mice took the longest to reach the criterion of the FR1 task (>70 rewards earned/30 minutes). Female FR1 to any hole Females born large for gestational age exhibited similar delays in acquiring FR1 criterion. •Overall the data for the male and female offspring born SGA and LGA showed similar patterns (offspring born small for gestational age were more prone to inattentiveness while offspring born large for gestational age were more prone to impulsivity) which suggests that maternal diet regardless of offspring sex is a significant contributor to attention and motivational deficits •However, females responded more prematurely overall than the males in both the control and the experimental groups suggesting that females may be more impulsive in general •This could have a significant implication for diagnosing and treating ADHD since many medications for ADHD treatment target the impulsivity and hyperactivity symptoms associated with the disorder. However, our mice models used to mimic maternal malnutrition exhibited markedly different deficits associated with ADHD depending on the maternal diet at time of gestation. This suggests that the varying symptoms of ADHD may be caused by separate mechanisms. The fixed ratio test utilized reinforcement in order to teach the mice that yoohoo would be dispensed when they registered a nose poke at the correct hole. When all the mice reached a baseline response criteria, they were tested on a progressive ratio schedule. Jordan Lidsky-Everson working under Teresa Reyes, Department of Pharmacology Standard Chow (CTL) 18.5% protein, 12% fat, 69.5% carb Low-protein (SGA) 8.5% protein, 22% fat, 69.5% carb High-fat (LGA) 18.5% protein, 60% fat, 20.5% carb All on Standard Chow wean (p21) to SC DBA/2J C57BL/6 X B6D2F1/J SC LP HF

Transcript of CURF Poster

Page 1: CURF Poster

Acknowledgements: College Alumni Society

Attention and Motivation in Female Offspring of Maternal Malnutrition

J.R. Lidsky-Everson, N. Grissom, and T. M. Reyes University of Pennsylvania, Perelman School of Medicine, Philadelphia PA

Previous data suggests that the maternal diet and gestational size of male mice greatly affects their attention and motivation. Using a 5-choice serial reaction time task to model attention, male mice born large for gestational age tended to have problems with impulse control while male mice born small for gestational age tended to be more inattentive. Because ADHD is more commonly diagnosed in males, we were interested in whether females exhibited similar deficits or if they were spared from these deficits. Maternal high fat and maternal low protein diets during gestation were used to model SGA and LGA. The 5-choice serial reaction time test was replicated with the female offspring. The results indicated that female mice characterized for reward, attention and impulse control function showed similar patterns of deficits to those of the male mice. This suggests that the attention and motivational deficits exhibited under maternal high fat and low protein diets are independent of sex differences.   METHODS

Progressive RatioFR1ABSTRACT

The mice were put through three operant behavior tasks. These tasks were conducted in a chamber that indicated a cue through illuminated holes in the back and dispensed yoohoo as a reward for appropriate responses. The chambers were equipped with 9 holes which were illuminated in accordance with the specific task being tested. Responses were recorded when nose pokes broke the infrared beams at the back of the chamber.

In the progressive ratio test, the animals were cued by a light in the back of the chamber at the center hole. However, in order to receive yoohoo, the mice had to break the infrared beam of the hole by registering nose pokes. At first the mice only had to nose poke once in order to receive the reward. After this was completed correctly three times, the mice were expected to respond progressively more times before they were rewarded.

Five-Choice Serial Reaction Time Test

Incorrect PrematureOmissionCorrect

During the 5-choice task, one of the five holes in the back of the chamber lit up after an intertrial interval. The mice had limited time to respond through a nose poke to the illuminated hole. If the trial was completed successfully (the mouse nose poked the correct hole), yoohoo was dispensed. The 5-choice test included five separate schedules which became increasingly more challenging for the animals by decreasing the amount of time the stimulus was activated.

The task measured attention by gathering both correct responses and incorrect responses. Error trials could be obtained through omission and commission. Omission was recorded when the mouse did not respond. Commission was recorded when either the mouse responded early or responded incorrectly.

Back of chamber

FR1 and Progressive Ratio

FR1

Trial number

123456789101112…n

Ratio for reward

111222444777…n

Progressive Ratio

5-Choice

The progressive ratio test examined how hard the mice were willing to work for a reward and measured motivational deficits. At some point the mice abandoned the task. The number of trials completed is an index of motivation for each mouse.

Male Progressive Ratio Test

Previously, the male LGA mice stopped this task the earliest indicating a decreased motivation to work for the reward.

Female Progressive Ratio Test

Females born large for gestational age exhibited similar behavior of decreased motivation.

Summary and Discussion

The 5-choice serial reaction time test measured attention and motivation by gathering both correct and incorrect responses. Omitted responses were an indication of inattention while incorrect and premature responses were an indication of impulsivity.

Male 5-choice serial reaction time test

Previously, male SGA mice tended to have higher rates of omitted trials which reflect inattention whereas LGA mice tended to have higher instances of incorrect responses and premature responses , which reflect impulsivity.

Female 5-choice serial reaction time test

COL 2015

Female offspring born small for gestational age made a significant amount of omission errors indicating inattention deficits. The offspring born large for gestational age showed a strong trend exclusively toward registering incorrect responses. Neither group showed signs of making excessively more premature responses than the control group.

Male FR1 to any hole

Previously, male HF mice took the longest to reach the criterion of the FR1 task (>70 rewards earned/30 minutes).

Female FR1 to any hole

Females born large for gestational age exhibited similar delays in acquiring FR1 criterion.

•Overall the data for the male and female offspring born SGA and LGA showed similar patterns (offspring born small for gestational age were more prone to inattentiveness while offspring born large for gestational age were more prone to impulsivity) which suggests that maternal diet regardless of offspring sex is a significant contributor to attention and motivational deficits

•However, females responded more prematurely overall than the males in both the control and the experimental groups suggesting that females may be more impulsive in general than the male offspring.

•This could have a significant implication for diagnosing and treating ADHD since many medications for ADHD treatment target the impulsivity and hyperactivity symptoms associated with the disorder. However, our mice models used to mimic maternal malnutrition exhibited markedly different deficits associated with ADHD depending on the maternal diet at time of gestation. This suggests that the varying symptoms of ADHD may be caused by separate mechanisms.

The fixed ratio test utilized reinforcement in order to teach the mice that yoohoo would be dispensed when they registered a nose poke at the correct hole. When all the mice reached a baseline response criteria, they were tested on a progressive ratio schedule.

Jordan Lidsky-Everson working under Teresa Reyes, Department of Pharmacology

Standard Chow (CTL)18.5% protein, 12% fat, 69.5% carb

Low-protein (SGA)8.5% protein, 22% fat, 69.5% carb

High-fat (LGA)18.5% protein, 60% fat, 20.5% carb

All on Standard Chow

wean(p21)to SCDBA/2J ♂ C57BL/6 ♀

XB6D2F1/J ♂

SC

LP

HF