Jan Scholz1, Kaitlyn Easson2, and Jason P Lerch1,3
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada, 2Department of Biomedical and Molecular Sciences, Queen's University, Toronto, ON, Canada, 3Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
Synopsis
The time course of the MRI changes associated with learning and experience is still unclear. Here we show with rapid in vivo imaging that brief periods of environmental enrichment of 24-48 h are associated with volumetric increases in a network of distinct brain areas. For the first time we show that the size of these changes is directly related to the length of the enrichment. Our results indicate that the volumetric increases might plateau after about 48 h. This suggests that studies of human brain plasticity, which have often imaged after several weeks of training, might have underestimated the speed of these structural changes.Purpose
The brain is known to change on a cellular level within 24-48 h in response to learning and experience
1,2. Recent studies suggest that early rapid experience-related structural changes might be detectable with MRI in humans
3. However, the time course and the cellular and molecular changes underlying the MRI changes are still unclear. Here we show that in vivo MR imaging in mice can reveal the time course of MRI changes that appear during the first 48 h in high temporal resolution.
Methods
MICE & MRI: A total of 56 male C57 mice were scanned twice at baseline and twice 4 days later. 30 mice were divided into three groups that received 24, 36 and 48 h of environmental enrichment prior to the third scan4. Mice were scanned at 90 µm3 isotropic voxel resolution using a T1-weighted manganese-enhanced MRI protocol (3D-gradient echo, TR/TE = 26/5.4 ms, matrix = 224 × 224 × 854, repeats = 5, total imaging time = 1.5 h).REGISTRATION & STATISTICS: Brain images were aligned using nonlinear image registration with iterative template refinement5 using the ANTS registration algorithm6. Jacobian determinants of the deformation fields were used in a mixed effects model of the group × time interaction.
Results
We found local volume increases in enriched mice compared to control mice in a number of brain areas (p<0.005, uncorrected). Volume increased in the dorsal striatum, the lateral septum, and the dentate gyrus of the hippocampus (Fig 1, A-C). We then investigated whether the extent of the changes was related to how long the mice were exposed to environmental enrichment. Within enriched mice the dentate gyrus of the hippocampus grew linearly with increasing enrichment duration (Fig 1, D). Plotting the time course of the changes for the dentate gyrus demonstrates the ‘dose’ effect of enrichment duration (Fig 2). For each enrichment duration we plot the volumes at the two post-enrichment scans (scans 3, 4). While there is no discernible increase in the 24 h group (-1%) a clear increase can be seen for the 36 h (5%) and 48 h (7%) groups.
Discussion & Conclusion
Here we demonstrate the first in vivo imaging results of rapid volumetric brain changes following environmental enrichment. These changes start to appear 24-36 h after the start of enrichment and seem to plateau after 48 h as suggested by the smaller increase from the 36 to the 48 h group compared to the increase from the 24 to the 36 h group. Ongoing research will test for the retention of the changes by follow the time course after the removal of the animal from the environmental enrichment.
Acknowledgements
No acknowledgement found.References
1. Xu, T., et al. Nature 462, 915–919 (2009). 2. Yang, G., et al. Nature 462, 920–924 (2009). 3. Sagi, Y., et al. Neuron 73, 1195–1203 (2012). 4. Scholz, J., et al. NeuroImage 109, 190–198 (2015). 5. Friedel, M., et al. Frontiers in Neuroinformatics 8, 67 (2014). 6. Avants, B.B., et al. Neuroinformatics 9, 381–400 (2011).