1. Impairment of consolidation and long-term retention of Motor Memories after
Traumatic Brain Injury
*S.C. Schwerin1,3, N. Datta2, M. Shindell2, S.L. Juliano2,3,, L.G. Cohen1
1. Human Cortical Physiology and Stroke Neurorehabilitation Section, NINDS, NIH, Bethesda MD
2.Anatomy, Physiology & Genetics, 3. Neuroscience, USUHS, Bethesda, MD, USA,
.
RESULTS
Mice: C57Bl6, 12 wk old adult males, ~24g
Groups:
●Control (surgically naïve)
●Sham (craniotomy only)
Memory deficits are typical after traumatic brain
injury. While weakness is not a prominent feature of
TBI, the impact of this condition on different stages of
motor skill learning is not known. In this study, we
investigated stages of motor learning using an
accelerated rotarod paradigm in a mouse model of
brain injury.
INTRODUCTION
CONCLUSIONS
ACKNOWLEDGEMENTS
●This work was supported by the Center for Neuroscience
and Regenerative Medicine, Henry M. Jackson Foundation,
grant # G1703N and the IRP, NINDS, NIH
Motor Training:
●Acclimation: 3 days prior to injury
-1 trial, 1 minute, at 4RPM
-Animals placed back on if fall
●Training: began on day 3 after injury
-4-40RPM over 2 minutes
-5 trials/day (T1-T5) for 5 days
-1st trial:60 sec at 4RPM before acceleration
-2nd-5th trial:10sec at 4RPM before acceleration
-Outcome parameter: time to fall off the rotarod or
do 1 full rotation
●Retention: tested 5 weeks after training completion
-1 trial, with 60 sec at 4RPM before acceleration
CCI Coordinates:
●Dominant hemisphere
(contralateral to dominant limb)
●Primary motor cortex
(caudal forelimb area)
●1.5 mm lateral to Bregma
Controlled Cortical Impact Parameters:
constant: 100ms dwell time, 15° angle, velocity: 5 m/s
●more mild TBI:
- impactor diameter: 1.5 mm
- depth: 1 mm
●more severe TBI:
- impactor diameter: 3 mm
- depth: 2mm
Stoelting Co., IL
METHODS
●Mice in both TBI groups showed deficits in
overnight consolidation on training days 2 and 3.
●Long term retention (5 weeks) was significantly
impaired in the more severe TBI group.
●Both TBI groups exhibited intact online learning.
●
●Results identified distinct behavioral differences
in stages of motor learning between control
animals and animals with varying degrees of
injury.
●Investigation of lesion extent and location is
under way.
Preliminary MRI Results
Handedness: determined prior to injury
●Mice food restricted to 90% original body weight
●15 min/day, placed in box and trained to reach, 10
reaches with either hand determined handedness
14 … 4 3 2 1
pre
handedness
rotarod
acclimation
Days
TBI
post
1 2 3 4 5 6 7 8 . . . 42
rotarod training
1 2 3 4 5
Retention
Timeline:
●more mild TBI
●more severe TBI
Figure 1. Accelerated Rotarod Motor Learning
MAX
Figure 1. Mice started the training (T1) and finished the training (T25) with similar skill level
between groups. A repeated measures ANOVA found a statistically significant main effect of
training trial [F(11.298, 467.377) = 10.385, P<0.005] and trial x group interaction [F(33.895,
467.377) = 1.858, P<0.005], indicating that while all groups showed improvement with training,
skill improved differently across groups. Note the remarkable overnight forgetting in both TBI
groups at T6 (mTBI p<0.05, sTBI p<.005) and T11 (mTBI p<.01, sTBI p<.001) (arrows) in the
presence of intact online learning. Performance at baseline and at the end of the 5th training day
were comparable.
Figure 2. Long Term Retention
Figure 2. At the retention testing day 5
weeks after the completion of training,
the control, sham, and mTBI groups
retained skill, but the sTBI group had a
significant reduction (p<.001) in skill
suggesting an impairment in long term
memory retention.
CCI
*
Preliminary results show no interhemispheric differences in
Sham and control animals, with progressively higher injury
in the mild and severe TBI groups.
In vivo MRI in a severe TBI animal: Interhemispheric
cortical volume was measured quantifying the cortical
tissue above the plane of the corpus collosum in the
coronal view of a T2 MRI. Areas damaged by CCI were
excluded from the measurement (lesion cavity and
hyper-intense regions).
* Lesion cavity
Hyperintense region of
dema
Isointense region
*
*
*
From Tennat KA, et al., 2011
ugo basile

2. The views presented here are those of the author and are not to be construed as official or
reflecting the views of the Uniformed Services University of the Health Sciences, the
Department of Defense or the U.S. Government.