Cerebral asymmetries in 12-week-old C57Bl/6J mice measured by magnetic resonance imaging

Asymmetries of multiple components of the rodent cerebrum have been described at various levels of organization. Yet, despite its ubiquitous nature, many confusing and sometimes contradictory reports regarding structural asymmetries in the rodent brain have been published. There is a need, therefore, for a whole-brain imaging analysis technique for asymmetry studies that is both accurate, reproducible and robust. To this end, a comprehensive three-dimensional examination of differences in brain structure in an inbred mouse strain was undertaken. The goal of this study was thus to use high-resolution magnetic resonance imaging to assess structural asymmetries in the adult C57Bl/6J mouse brain. Fixed brain T2-weighted images of 20 male C57Bl/6J mice were acquired on a 7T scanner at 32 microm isotropic resolution. We used voxel-based analyses to examine structural asymmetries throughout the whole mouse brain. The striatum, medial-posterior regions of the thalamus, and motor, sensorimotor, and visual cortex were found to be asymmetrical. The most significant asymmetry was found in the hippocampus and, specifically, the dentate gyrus. In each case, the left region was larger than the right. No other regions of the mouse brain showed structural asymmetry. The results in the dentate gyrus were confirmed using stereology, revealing a correlation of r=0.61 between magnetic resonance and stereological measures. Hippocampal, along with cortical asymmetry, has been discussed repeatedly in the literature, yet a clear pattern of directionality, until this point, has not been described. The findings of asymmetry in the striatum and absence of asymmetry in the rest of the brain are novel and show the advantage of using the whole-brain three-dimensional techniques developed herein for assessing asymmetry.

[1]  Daniel Bandy,et al.  Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease , 1998, Annals of neurology.

[2]  A. Galaburda,et al.  Neocortical asymmetry and open-field behavior in the rat , 1984, Experimental Neurology.

[3]  Lutz Jäncke,et al.  A voxel-based approach to gray matter asymmetries , 2004, NeuroImage.

[4]  M. Diamond,et al.  Age-related morphologic differences in the rat cerebral cortex and hippocampus: Male-female; right-left , 1983, Experimental Neurology.

[5]  Süleyman Kaplan,et al.  Numerical density of pyramidal neurons in the hippocampus of 4 and 20 week old male and female rats , 2003 .

[6]  N. Geschwind,et al.  Cerebral lateralization. Biological mechanisms, associations, and pathology: I. A hypothesis and a program for research. , 1985, Archives of neurology.

[7]  W H Theodore,et al.  Measurement of whole temporal lobe and hippocampus for MR volumetry , 1993, Neurology.

[8]  D R Fish,et al.  Methods for normalization of hippocampal volumes measured with MR. , 1995, AJNR. American journal of neuroradiology.

[9]  R. M. Henkelman,et al.  Development of a high resolution three-dimensional surgical atlas of the murine head for strains 129S1/SvImJ and C57Bl/6J using magnetic resonance imaging and micro-computed tomography , 2007, Neuroscience.

[10]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[11]  A. Schleicher,et al.  Structural Asymmetries in the Human Forebrain and the Forebrain of Non-human Primates and Rats , 1996, Neuroscience & Biobehavioral Reviews.

[12]  Alan C. Evans,et al.  Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans. , 2001, Cerebral cortex.

[13]  Sophia Vinogradov,et al.  Anterior hippocampal volume reduction in male patients with schizophrenia , 2003, Schizophrenia Research.

[14]  J. R. Hughes Cerebral lateralization: biological mechanisms, associations and pathology , 1987 .

[15]  S. Strakowski,et al.  Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. , 1999, Archives of general psychiatry.

[16]  Scott Hamilton,et al.  In Vivo 3D Digital Atlas Database of the Adult C57BL/6J Mouse Brain by Magnetic Resonance Microscopy , 2008, Frontiers in neuroanatomy.

[17]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[18]  J. Crawley Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests 1 Published on the World Wide Web on 2 December 1998. 1 , 1999, Brain Research.

[19]  M. Diamond,et al.  The rat amygdaloid nucleus: A morphometric right-left study , 1984, Experimental Neurology.

[20]  B. Milner,et al.  Disorders of learning and memory after temporal lobe lesions in man. , 1972, Clinical neurosurgery.

[21]  A. Toga,et al.  Mapping brain asymmetry , 2003, Nature Reviews Neuroscience.

[22]  Robert J Zatorre,et al.  Asymmetries of the planum temporale and Heschl's gyrus: relationship to language lateralization. , 2006, Brain : a journal of neurology.

[23]  Bryan Kolb,et al.  Asymmetry in the cerebral hemispheres of the rat, mouse, rabbit, and cat: The right hemisphere is larger , 1982, Experimental Neurology.

[24]  James J. Valdes,et al.  Lateralization of norepinephrine, serotonin and choline uptake into hippocampal synaptosomes of sinistral rats , 1981, Physiology & Behavior.

[25]  Natasa Kovacevic,et al.  Neuroanatomical differences between mouse strains as shown by high-resolution 3D MRI , 2006, NeuroImage.

[26]  E. Faught,et al.  Volumetric MRI of the limbic system: anatomic determinants , 1998, Neuroradiology.

[27]  S. D. Glick,et al.  Mast cells in rat thalamus: Nuclear localization, sex difference and left-right asymmetry , 1984, Brain Research.

[28]  Alan C. Evans,et al.  A three-dimensional MRI atlas of the mouse brain with estimates of the average and variability. , 2005, Cerebral cortex.

[29]  Jonathon Bishop,et al.  Magnetic resonance imaging for detection and analysis of mouse phenotypes , 2005, NMR in biomedicine.

[30]  Robert L. Collins,et al.  Structural asymmetries in brains of mice selected for strong lateralization , 1984, Brain Research.

[31]  A. Oke,et al.  Hemispheric asymmetry of norepinephrine distribution in rat thalamus , 1980, Brain Research.

[32]  Douglas L Rosene,et al.  Asymmetry of neuron numbers in the hippocampal formation of prenatally malnourished and normally nourished rats: A stereological investigation , 2006, Hippocampus.

[33]  R. Collins,et al.  ORIGINS OF THE SENSE OF ASYMMETRY: MENDELIAN AND NON‐MENDELIAN MODELS OF INHERITANCE * , 1977, Annals of the New York Academy of Sciences.

[34]  Glenna A. Dowling,et al.  Morphologic cerebral cortical asymmetry in male and female rats , 1981, Experimental Neurology.

[35]  S. Kaplan,et al.  Brief Communication SEX DIFFERENCES AND RIGHT-LEFT ASYMMETRIES IN RAT HIPPOCAMPAL COMPONENTS , 2002, The International journal of neuroscience.

[36]  Glenna A. Dowling,et al.  A morphological study of male rat cerebral cortical asymmetry , 1982, Experimental Neurology.

[37]  M. Baulac,et al.  MR determination of hippocampal volume: comparison of three methods. , 1996, AJNR. American journal of neuroradiology.

[38]  J. van Pelt,et al.  Sex-difference and left-right asymmetries in the prefrontal cortex during postnatal development in the rat. , 1984, Brain research.

[39]  J. Michael Tyszka,et al.  Statistical diffusion tensor histology reveals regional dysmyelination effects in the shiverer mouse mutant , 2006, NeuroImage.

[40]  J. Frahm,et al.  High-resolution 3D MRI of mouse brain reveals small cerebral structures in vivo , 2002, Journal of Neuroscience Methods.

[41]  F Andermann,et al.  Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging , 1992, Neurology.

[42]  R. Mark Henkelman,et al.  High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice , 2008, NeuroImage.

[43]  Jason P. Lerch,et al.  High Throughput Microimaging of the Mouse Brain , 2010 .

[44]  Mark J. West,et al.  Asymmetry in the hippocampal region specific for one of two closely related species of wild mice , 1987, Brain Research.

[45]  Robert L. Collins,et al.  The effects of early experience on callosal development and functional lateralization in pigmental BALB/c mice , 1992, Behavioural Brain Research.

[46]  B. McEwen,et al.  Modification of Social Memory, Hypothalamic-Pituitary-Adrenal Axis, and Brain Asymmetry by Neonatal Novelty Exposure , 2003, The Journal of Neuroscience.

[47]  G. Allan Johnson,et al.  Neuroanatomical phenotypes in the Reeler mouse , 2007, NeuroImage.

[48]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[49]  M. Diamond,et al.  Morphologic hippocampal asymmetry in male and female rats , 1982, Experimental Neurology.

[50]  R. Mark Henkelman,et al.  Sexual dimorphism revealed in the structure of the mouse brain using three-dimensional magnetic resonance imaging , 2007, NeuroImage.

[51]  A. Sahgal Neurobiology of the Hippocampus, W. Seifert (Ed.). Academic Press (1983), xxviii + 632, ISBN: 0 126 34880 4 , 1984 .