“Where can I find Bregma?”
We get this question frequently from researchers who are using the Allen Mouse Brain Adult Reference Atlas in the Common Coordinate Framework (CCF), which can be viewed in the Allen Brain Explorer. Bregma is the area of the mammalian skull where the sagittal and coronal sutures joining the parietal and frontal bones come together. If you understand how the reference atlas and CCF were created, it will make sense why there are no Bregma coordinates shown in the web browser or planar views of the atlas or CCF.
The Allen Reference Atlas and CCF were developed to give a detailed view of the cellular level anatomy of the mouse brain, to provide data-driven anatomical annotations using axonal projection patterns and gene expression, combined with analysis of classical neuroanatomy and expert opinion. The CCF was created using an average of over 1600 individual adult mouse brains, from coronal planar images. Each one of those brains was dissected from a skull, and every skull has a slightly different Bregma location; hence the CCF does not have a single brain-in-skull as a source (which would have a corresponding Bregma coordinate), but is made from brains out-of-skull that have been registered to achieve an ‘average’ volume that is defined by the brain itself, ex cranio. Detailed methods on the creation of the CCF are in the Technical Documentation for the Allen Mouse Brain Connectivity Atlas.
In addition, the CCF reference space is created using PFA-fixed mouse brains, so the average size is about 30% smaller than an in cranio mouse brain. For these reasons, spatial landmarks such as Bregma on are not provided with the CCF or 3D reference atlas, as that information was not gathered in the creation of the reference volume displayed, and estimating a location might not allow researchers the accuracy needed for working in vivo.
Many of our Technical Documents describe the experimental procedures we use, that do reference Bregma; a list of those documents can be accessed through the Help search system. We include measured coordinates for Bregma as it relates to stereotaxic injection targets for experiments in the Connectivity Atlas; an example of this data is shown in the AAV Injection Summary section. There is also a description of the creation of the initial version of the CCF in the 2014 publication by Oh et al, A Mesoscale Connectome of the Mouse Brain.
We realize that including even a statistical estimate for the Bregma location may help researchers, and we are looking into ways we can provide that information for future datasets. We could extrapolate the “probability” of the Bregma location based on the variability we measured from many brains, but it is important to remember that this reference could only be used as a rough guide - and more importantly, the CCF itself is not derived from one mouse, but reflects an average of many brains.
Other researchers have developed tools that may be useful in evaluating mouse brain volume data that is not mapped to Bregma; the Allen Institute did not develop or endorse these, but it may be worthwhile to view what is available:
Feel free to add links to this thread, regarding other resources that might allow researchers to infer Bregma, or your thoughts on how to infer practical landmarks for studies that need cranial references for brain area targeting.