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 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
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 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 ♀
X
B6D2F1/J ♂
SC
LP
HF