Morphological and behavioral characterization of adult mice deficient for SrGAP3.

SrGAP3 belongs to the family of Rho GTPase proteins. These proteins are thought to play essential roles in development and in the plasticity of the nervous system. SrGAP3-deficient mice have recently been created and approximately 10 % of these mice developed a hydrocephalus and died shortly after birth. The others survived into adulthood, but displayed neuroanatomical alteration, including increased ventricular size. We now show that SrGAP3-deficient mice display increased brain weight together with increased hippocampal volume. This increase was accompanied by an increase of the thickness of the stratum oriens of area CA1 as well as of the thickness of the molecular layer of the dentate gyrus (DG). Concerning hippocampal adult neurogenesis, we observed no significant change in the number of proliferating cells. The density of doublecortin-positive cells also did not vary between SrGAP3-deficient mice and controls. By analyzing Golgi-impregnated material, we found that, in SrGAP3-deficient mice, the morphology and number of dendritic spines was not altered in the DG. Likewise, a Sholl-analysis revealed no significant changes concerning dendritic complexity as compared to controls. Despite the distinct morphological alterations in the hippocampus, SrGAP3-deficient mice were relatively inconspicuous in their behavior, not only in the open-field, nest building but also in the Morris water-maze. However, the SrGAP3-deficient mice showed little to no interest in burying marbles; a behavior that is seen in some animal models related to autism, supporting the view that SrGAP3 plays a role in neurodevelopmental disorders.

Automated analysis protocol for high resolution BOLD-fMRI mapping of the fingertip somatotopy in brodmann area 3b.

BACKGROUND: To introduce a standardized and automatized method for functional MRI (fMRI) examinations of the cortical sensory somatotopy in large samples for investigations of the fingertip somatotopy in the primary somatosensory cortex. METHODS: At 3 Tesla, T2* (spin-spin relaxation time) weighted images (gradient-echo echo planar imaging, voxel size 1.5 × 1.5 × 2 mm3) were acquired during stimulation of the finger tips for thumb, index and middle finger on both hands, in a group of 18 healthy participants. In addition, structural T1 weighted (magnetization prepared rapid gradient echo, isotropic voxel size 1 mm) and MR-angiography (time of flight, voxel size 0.26 × 0.26 × 0.5 mm3) images were recorded. Boundary based register served to combine movement correction and registration in FreeSurfer Functional analysis stream (FS-Fast), resulting in fine scale corrections, as revealed with FSL Possum (FSL FMRIB Software Library Physics-Oriented Simulated Scanner for Understanding MRI) simulations. Automated data analysis was achieved by inclusion of cytoarchitectonic probability maps for calculation of functional activation in Brodmann area 3b. Draining vessel artifacts were identified using the peak value approach and the MR-angiography. Distances were computed as the shortest connection within the gray matter. RESULTS: The fMRI somatotopic maps agreed with the expected fingertip somatotopy in 63% of the investigated subjects, an improvement of 34% compared with FS-Fast. Artifacts have been removed completely. Adjacent fingertips showed average distances of 8 ± 4.3 mm, and between thumb and middle finger 13.4 ± 4.8 mm was found. Distances for both hands were similar as expected from the characteristics of the fingertip spatial tactile resolution. CONCLUSION: The introduced evaluation procedure allowed automated analysis of the fingertip representation in excellent agreement with preceding results.

Post-mortem magnetic resonance microscopy (MRM) of the murine brain at 7 Tesla results in a gain of resolution as compared to in vivo MRM.

Small-animal MRI with high field strength allows imaging of the living animal. However, spatial resolution in in vivo brain imaging is limited by the scanning time. Measurements of fixated mouse brains allow longer measurement time, but fixation procedures are time consuming, since the process of fixation may take several weeks. We here present a quick and simple post-mortem approach without fixation that allows high-resolution MRI even at 7 Tesla (T2-weighted MRI). This method was compared to in vivo scans with optimized spatial resolution for the investigation of anesthetized mice (T1-weighted MRI) as well as to ex situ scans of fixed brains (T1- and T2-weighted scans) by using standard MRI-sequences, along with anatomic descriptions of areas observable in the MRI, analysis of tissue shrinkage and post-processing procedures (intensity inhomogeneity correction, PCNN3D brain extract, SPMMouse segmentation, and volumetric measurement). Post-mortem imaging quality was sufficient to determine small brain substructures on the morphological level, provided fast possibilities for volumetric acquisition and for automatized processing without manual correction. Moreover, since no fixation was used, tissue shrinkage due to fixation does not occur as it is, e.g., the case by using ex vivo brains that have been kept in fixatives for several days. Thus, the introduced method is well suited for comparative investigations, since it allows determining small structural alterations in the murine brain at a reasonable high resolution even by MRI performed at 7 Tesla.