Manganese-enhanced MRI reveals structural and functional changes in the cortex of Bassoon mutant mice.

Manganese-enhanced magnetic resonance imaging (ME-MRI) was used to analyze the brain architecture in mice lacking the functional presynaptic active zone protein Bassoon. Anatomical characterization revealed a significant increase in the total brain volume in Bassoon mutants as compared with wild-type mice, which is mainly caused by changes in cortex and hippocampus volume. The measured enlargement in cortical volume coincides with an altered Mn2+ distribution within cortical layers as visualized by T1-weighted magnetic resonance imaging. Two days after manganese application, the cortex of Bassoon mutant mice appeared more laminated in ME-MRI, with an enhanced accumulation of manganese in deep, central, and superficial cortical cell layers. Whereas morphologically the cortical lamination is not affected by the absence of a functional Bassoon, an altered basal activation pattern was found in the cortex of the mutant mice both by metabolic labeling with [14C]-2-deoxyglucose and histochemical detection of the potassium analogue thallium uptake. Consequently, the results indicate that the absence of the functional presynaptic protein Bassoon causes disturbance in the formation of normal basal cortical activation patterns and thereby in the functional cortical architecture. Furthermore, this study shows that ME-MRI can become a valuable tool for a structural characterization of genetically modified mice.

[1]  Josef Ammermüller,et al.  The Presynaptic Active Zone Protein Bassoon Is Essential for Photoreceptor Ribbon Synapse Formation in the Retina , 2003, Neuron.

[2]  Atsushi Takeda,et al.  Manganese action in brain function , 2003, Brain Research Reviews.

[3]  H. D. Morris,et al.  Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat , 2003, Neuroscience.

[4]  D. Turnbull,et al.  In vivo auditory brain mapping in mice with Mn-enhanced MRI , 2005, Nature Neuroscience.

[5]  M. Verhoye,et al.  In vivo manganese-enhanced magnetic resonance imaging reveals connections and functional properties of the songbird vocal control system , 2002, Neuroscience.

[6]  L. Sokoloff,et al.  Measurement of local cerebral glucose utilization and its relation to local functional activity in the brain. , 1991, Advances in experimental medicine and biology.

[7]  L. Missiaen,et al.  The Ca2+/Mn2+ pumps in the Golgi apparatus. , 2004, Biochimica et biophysica acta.

[8]  Henning Scheich,et al.  High-resolution mapping of neuronal activity by thallium autometallography , 2004, NeuroImage.

[9]  W. Löscher,et al.  The central piriform cortex: anatomical connections and anticonvulsant effect of gaba elevation in the kindling model , 2004, Neuroscience.

[10]  A. Hazell,et al.  Astrocytes and manganese neurotoxicity , 2002, Neurochemistry International.

[11]  B L Trus,et al.  Image averaging of flexible fibrous macromolecules: the clathrin triskelion has an elastic proximal segment. , 1991, Journal of structural biology.

[12]  M. Ingvar,et al.  Truncation of the Shaker‐like voltage‐gated potassium channel, Kv1.1, causes megencephaly , 2003, The European journal of neuroscience.

[13]  A. Grippo,et al.  Manganese(II) dynamics and distribution in glial cells cultured from chick cerebral cortex , 1989, Neurochemical Research.

[14]  J. Cooper,et al.  FGFR3 regulates brain size by controlling progenitor cell proliferation and apoptosis during embryonic development. , 2005, Developmental biology.

[15]  A. C. Meyer,et al.  Functional Inactivation of a Fraction of Excitatory Synapses in Mice Deficient for the Active Zone Protein Bassoon , 2003, Neuron.

[16]  Robert A Yokel,et al.  Manganese distribution across the blood-brain barrier III. The divalent metal transporter-1 is not the major mechanism mediating brain manganese uptake. , 2004, Neurotoxicology.

[17]  Oliver Natt,et al.  In vivo 3D MRI staining of the mouse hippocampal system using intracerebral injection of MnCl2 , 2004, NeuroImage.

[18]  Alex M Thomson,et al.  Excitatory and inhibitory connections show selectivity in the neocortex , 2005, The Journal of physiology.

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

[20]  M. Castro-Alamancos,et al.  Leading role of the piriform cortex over the neocortex in the generation of spontaneous interictal spikes during block of GABAA receptors , 2004, Neuroscience.

[21]  N. Ziv,et al.  Cellular and molecular mechanisms of presynaptic assembly , 2004, Nature Reviews Neuroscience.

[22]  M. Carson,et al.  Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. , 1993, Neuron.

[23]  Alan P. Koretsky,et al.  Tracing Odor-Induced Activation in the Olfactory Bulbs of Mice Using Manganese-Enhanced Magnetic Resonance Imaging , 2002, NeuroImage.

[24]  R. Jacobs,et al.  In vivo trans‐synaptic tract tracing from the murine striatum and amygdala utilizing manganese enhanced MRI (MEMRI) , 2003, Magnetic resonance in medicine.

[25]  M. Carson,et al.  Insulin-like growth factor I increases brain growth and central nervous system myelination in tTransgenic mice , 1993, Neuron.

[26]  Anna Devor,et al.  In vivo tracing of major rat brain pathways using manganese-enhanced magnetic resonance imaging and three-dimensional digital atlasing , 2003, NeuroImage.

[27]  C. Wiessner,et al.  Three‐dimensional MRI of cerebral projections in rat brain in vivo after intracortical injection of MnCl2 , 2003, NMR in biomedicine.

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

[29]  J. Roth,et al.  Iron interactions and other biological reactions mediating the physiological and toxic actions of manganese. , 2003, Biochemical pharmacology.

[30]  Xin Yu,et al.  Manganese‐enhanced magnetic resonance imaging (MEMRI) of mouse brain development , 2004, NMR in biomedicine.

[31]  Ichio Aoki,et al.  In vivo detection of neuroarchitecture in the rodent brain using manganese-enhanced MRI , 2004, NeuroImage.

[32]  C. Garner,et al.  The presynaptic cytomatrix of brain synapses , 2001, Cellular and Molecular Life Sciences CMLS.

[33]  M. Verhoye,et al.  In vivo dynamic ME‐MRI reveals differential functional responses of RA‐ and area X‐projecting neurons in the HVC of canaries exposed to conspecific song , 2003, The European journal of neuroscience.

[34]  L. Donahue,et al.  Megencephaly: a new mouse mutation on chromosome 6 that causes hypertrophy of the brain , 1996, Mammalian Genome.

[35]  A. Egner,et al.  Hair cell synaptic ribbons are essential for synchronous auditory signalling , 2005, Nature.

[36]  R. Pautler In vivo, trans‐synaptic tract‐tracing utilizing manganese‐enhanced magnetic resonance imaging (MEMRI) , 2004, NMR in biomedicine.

[37]  Ichio Aoki,et al.  Manganese‐enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations , 2004, NMR in biomedicine.

[38]  J Hennig,et al.  RARE imaging: A fast imaging method for clinical MR , 1986, Magnetic resonance in medicine.

[39]  Robert A Yokel,et al.  Manganese distribution across the blood-brain barrier. I. Evidence for carrier-mediated influx of managanese citrate as well as manganese and manganese transferrin. , 2003, Neurotoxicology.

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

[41]  J. Frahm,et al.  Mapping of retinal projections in the living rat using high‐resolution 3D gradient‐echo MRI with Mn2+‐induced contrast , 2001, Magnetic resonance in medicine.

[42]  A. Koretsky,et al.  Manganese ion enhances T1‐weighted MRI during brain activation: An approach to direct imaging of brain function , 1997, Magnetic resonance in medicine.

[43]  W. Löscher,et al.  THE ROLE OF THE PIRIFORM CORTEX IN KINDLING , 1996, Progress in Neurobiology.

[44]  T. Hökfelt,et al.  MRI and in situ hybridization reveal early disturbances in brain size and gene expression in the megencephalic (mceph/mceph) mouse , 2003, The European journal of neuroscience.