CHEMOARCHITECTONIC ATLAS OF THE DEVELOPING MOUSE BRAIN PDF

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Abstract Stereotaxic operations of the mouse brain are critically important for various types of neuroscience research studies, which include electrical recording of neural activities or site-targeted injection of stem cells, chemical tracers, and vectors, to name a few.

To guide such operations, two-dimensional histology-based mouse brain atlases, such as the Paxinos and Franklin atlas, are widely used. Recently, computed tomography CT and magnetic resonance imaging MRI based hybrid three-dimensional 3D atlases of developing mouse brains have been introduced. In this study, a new stereotaxic guidance software, called AtlasGuide, is introduced, which was developed to fully utilize the benefits of the 3D atlases for high-precision stereotaxic targeting.

The AtlasGuide software provides functions to visualize oblique needle paths in 2D and 3D views, which allow investigators to simultaneously examine brain structures that could be damaged by the needle path and optimize the injection angles for high-precision trajectory selection through critical neural tissue.

It allows reorientation and scaling of the atlases dynamically to match the orientation of the animal brain prepared for surgery, thereby eliminating the need to manually align the subject to the atlas, a procedure which is essential while using conventional 2D atlases. In addition, the software enables loading user-defined atlases when researchers need image-based guidance for different age groups, strains, or species.

Keywords: stereotaxic guidance, surgical, atlas, mouse, brain 1. Introduction The goal of this study was to develop a stereotaxic navigation and user-interface software with integrated electronic mouse brain atlases for image-guided stereotaxic surgical operations.

The development of genetic engineering technology in the early s has brought the mouse into a prominent role for investigations of the mammalian central nervous system. In these mouse-based neuroscience studies, stereotaxic surgical operations are essential for targeted delivery of chemicals, vectors, cells, or implantation of electrodes at specific locations in the brain Athos and Storm, ; Cetin et al.

Because the targeted delivery is essentially a blind operation, stereotaxic atlases are an essential resource for these surgeries. Namely, the coordinates of specific brain structures of interest are identified from a stereotaxic atlas, and the needle or electrode is inserted to the targeted location.

There are several histology-based atlases that are available for anatomic delineation of the mouse brain Dong, ; Jacobowitz and Abbott, ; Paxinos and Franklin, ; Sidman et al.

Of these, currently the Paxinos and Franklin atlas Paxinos and Franklin, in stereotaxic coordinates is almost exclusively used for the guidance of stereotaxic surgical procedures in the adult mouse brain Messier et al. However, histology-based atlases, while they have excellent proven values, also have several limitations. First, they cover only adult mouse brains and at present there is no histology-based stereotaxic atlas available for neonate brains.

Second, the two-dimensional histology-based atlases cover only a limited number of slice orientations and locations. From a series of 2D slices, it is difficult to design an oblique needle path in order to avoid damaging important brain structures. Third, the tissue fixation and sectioning process can introduce potential inaccuracy in the precise stereotaxic brain coordinates.

In recent years, several 3D mouse brain atlases based on high-resolution magnetic resonance imaging MRI have been developed Dorr et al. Specifically for stereotaxic operations, atlases based on MRI and micro-computed tomography micro-CT have been recently introduced Aggarwal et al.

Because stereotaxic surgery relies on using external skull-surface landmarks to estimate the locations of underlying brain structures, the CT and MRI co-registered atlases can provide 3D stereotaxic coordinates of brain structures identified with MRI contrasts, relative to cranial landmarks that can be delineated based on micro-CT contrasts.

In this study, we introduce a new navigation software developed for image-guided stereotaxic operations with integrated three-dimensional electronic atlases of mouse brains at different developmental stages. Based on the hybrid atlases with high anatomical fidelity, we developed a stereotaxic guidance software, called AtlasGuide, which provides a user-interface for atlas navigation with several advanced features to utilize the potential of the 3D atlases.

In addition, the AtlasGuide software allows users to load animal brain images from their specific studies, extending its capability to other ages, strains or species. Theory and Methods 2. At each age, T2-weighted and diffusion tensor MR images acquired at a resolution of 0.

In addition to single-subject atlases for developmental stages, for the adult mouse brain a second-level population-based in vivo MRI atlas was generated, and a postmortem distortion-corrected atlas was developed by nonlinear deformation of the high-resolution ex vivo data to the in vivo atlas. This procedure was implemented to; i correct for postmortem fixation-related tissue shrinkage, and ii remove any sample-specific anatomical bias, in order to achieve improved anatomical fidelity and accuracy of stereotaxic targeting in the adult mouse brain.

Structural Segmentation For the adult mouse brain atlas, 46 anatomical structures were manually segmented using ROIEditor www. Table 1 List of three-dimensionally segmented structures for the adult mouse brain atlas. Each structure is segmented separately for the left and right hemispheres. List of segmented structures for the adult brain Abbreviation.

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