A brain atlas is a valuable tool containing pictures of brain sections in different anatomical orientations (three-dimensional space; coronal, sagittal and axial planes), with the coordinates of relevant brain structures to define their outlines or volumes. An atlas enables the researcher to calculate stereotaxic coordinates for a variety of stereotaxic procedures to accurately target deep brain structures for recording or lesioning (1–4). This atlas when combined with electrophysiological data helps to better understand the functional activity in brain networks across species (5). Having a highly precise and consistent atlas assures consistency in defining the boundaries of various brain structures between publications from different researchers (6). In addition, atlas and templates are necessary to improve understanding of neuroanatomical structures, leading to advancements in the field of neurology, and neurosurgery and to aid translational neuroscience research.

Among the various animal species used in neuroscience, rodents are the most common. Other used species include domestic animals such as pigs, goats, and sheep, and those that are also companion animals such as horses, dogs and cats. Stereotaxic and automatic tissue segmentation systems with varied detail have been developed for humans, non-human primates, dogs, cats and rodents, but not for sheep. A detailed brain atlas exists for humans, the Allen Human Brain Atlas; for rats, the Rat Brain in Stereotaxic Coordinates (7); for mouse, Allen Brain Atlas: Mouse Brain; for rhesus macaques, NIH Blueprint Non-Human Primate (NHP) Atlas; for long-tailed macaque monkeys (4); for domestic species such as the pig (1), dog (8–10), cat (5), and horse. Some example two-dimensional images of brain coronal and sagittal sections of various animal species is shown in Figure 1. Unfortunately, to our knowledge, no such detailed atlas is available for sheep.

The sheep (Ovis aries) is an attractive and convenient animal model for mapping human disorders, particularly for neurosurgical and neuropathological research. Physiological and neuroanatomical similarities between sheep and humans, such as cerebral white matter distribution (11), gyrencephalic cerebral cortexes, thick meninges, and highly distinct sulci and gyri (12–14), make sheep an acceptable large brain animal model for neurological research. Sheep cerebral cortices contain four lobes defined by external landmarks, similar to those of humans (15). Furthermore, the sub-cortical structures in particular, the dorsal striatum, are in two separate sections; caudate nucleus and putamen in sheep, similar to humans (14, 16). In addition, the relatively round skull of the sheep is comparable to the human head, unlike pigs which have a flat and thick skull (17). Therefore, the brains of sheep may have distinct anatomical advantages over small brains for translational research. A detailed review of neuroanatomy is beyond the scope of this paper, but clinically relevant areas are compared briefly in Table 1. Other benefits of using sheep such as greater acceptability to animal ethics committee compared to companion animals and primates, easily available, less expensive, reasonably outbreed, easy management, environmental enrichment not required as they live in their natural pasture, make sheep advantageous an experimental model for translational research over large animal species, in particular primates.

Despite similar neuroanatomical and neurofunctional features between sheep and human brains, and the relatively low cost of the sheep as a model for teaching human-like brain anatomy, very little is known about the ovine brain anatomical relationships, and a detailed sheep atlas is scarce. The only available atlases are either limited to specific brain areas (35), consist of a series of gross photographs of sheep brain (36), or provide labeled coronal sections (both cell and fiber stain) but do not offer standard stereotaxic coordinates and reference system (e.g., The Michigan histological sheep brain atlas; https://brains.anatomy.msu.edu/brains/sheep/index.html; retrieved on May 12, 2022). Although there is a sheep atlas with a coordinate system (covering a few brain areas), histology sections with labeled brain structures (as in the Michigan histological data atlas; but not the standard stereotaxic coordinates/reference system) and neuroimaging atlas there is no comprehensive atlas that actually combines all these features to enable defined regions to be easily localized. Therefore, the neuroscience research community would be benefitted by having a detailed sheep atlas that combines both neuroanatomical regions on both histology (as in the Michigan histological data atlas) as well as neuroimaging (MRI atlases)to enable defined regions to be easily localized.

The study of the cortico-spinal or pyramid tract fibers of the sheep brain can be dated back to the late 18th century (the literature refers to 1877 by Atruro Maracacci)(37). Researchers made strenuous efforts to map the brain and anatomical areas and to partition these based on cytoarchitectonic information available at that early stage. Most of the early studies in sheep were based on electrical or mechanical stimulation of the different brain regions and mapping with a pattern of body response to stimuli (37–39). In 1967, Richard published the first hard copy sheep atlas, “Atlas stereotaxique du cerveau de beria.” However, the atlas was written in the French language and was limited to specific brain areas, including subcortical structures such as the thalamus, hippocampus, and hypothalamus (35). The stereotaxic brain atlas in English was prepared by McKenzie and Smith in 1973 from female merino sheep and was used by others in guiding electrical stimulation of the brain, diencephalic lesions, and intracerebroventricular chemical stimulations (40). Opdam and colleagues, first reported the sheep (merino) model of focal epilepsy (penicillin-induced) in 2002 using concurrent EEG and fMRI (41). The localization of coordinates for surgical placement and electrodes was based on the anatomic atlas of the sheep brain, however, the authors did not relate the details of the stereotaxic reference systems to the distinct anatomical structures identified from their experimental findings to help map the findings to the structures found in the human brain.

At least 80–90% of novel therapeutic agents tested on many rodents are found to be ineffective when translating therapies into clinical research. One of the factors could be the inappropriate selection of a suitable experimental animal model for translational research. In addition, regulatory authorities expect therapeutic agents and medical device testing on at least one small rodent and large non-rodent gyrencephalic species prior to clinical trials. As neuroscience becomes increasingly advanced, highly accurate and consistent brain atlases are needed for high-precision neuroscience experimentation. The neuroscience research community would be benefitted by having a detailed ovine brain atlas with coordinates that combine both neuroanatomical regions on both histology (as in the Michigan histological data atlas) as well as neuroimaging (MRI atlases) to enable defined regions to be easily localized. Although there are some still existing limits such as the scarcity of neurochemical and electrophysiological data, as well as the difficulty and high cost of performing transgenesis experiments, we believe that creating a detailed ovine brain atlas consisting of well-defined brain regions (easily identifiable) and somatotopic organization (similar to the available human and rodents atlas) is necessary for clinically relevant translational neuroscience and neurological research. Such an atlas would allow for detailed regional analysis and easier surgical manipulation, facilitate the generalizability and comparability of experimental results across studies and laboratories and reduce the requirement for higher resolution imaging. This would be a significant piece of research. Such a tool would be extremely valuable for research in the next 5 to 10 years using sheep as a large animal non-primate model for translational neurological research.

Conceptualization and writing—original draft: AB. Visualization and writing—review and editing: AB and JR. All authors contributed to the article and approved the submitted version.

This work was supported by the Neurological Foundation New Zealand grant 2130PRG.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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