Current Views on Comparative Neuroanatomy in Common but Neglected Mammals

Dear Colleagues,

The scope of this special issue is to emphasize current research in the comparative anatomy of the nervous system organization in common but neglected mammals, integrating the unique features that they have acquired through adaptations to their environment.

The aim is to collect neuroanatomical studies on different mammalian species living in any ecosystem or medium on the planet (land, water, and air), with special regards to domestic mammals such as horse, bovine, swine, sheep, llama, and alpaca.

The overwhelming majority of classic and modern neuroscience studies have involved either rodents or primates—the former for their obvious management advantages, reduced body size, and smaller brain size; the latter for their phylogenetic proximity to humans.

This paradigm has brought about tremendous progress in our understanding of the mammalian nervous system, but voices have been raised on why this dominance came to be [1,2,3,4].

The mammalian class has conquered every major ecosystem on the planet, every medium (chiropterans in air, marine mammals in water, and obviously wild and domestic mammals on land), raising multiple questions regarding their relative cortical development, parallel evolution, and more generally on the emergence of unique features in the organization of their respective nervous systems.

In this context, the lissencephalic brain of rodents poorly depicts the sophisticated diversity of the neocortical circuitry and functions of herbivores, carnivores, and primates.

There is therefore still a great deal left to study. Although to a certain extent, bats in air and cetaceans in water have generated some research, on land, domestic mammals such as perissodactyls (equines), suinids (pigs), and domestic ruminants (cattle and sheep, alpaca and llama) remain quite understudied.

Yet, comparative neuroanatomy has the potential to help solve some crucial interrogations in neuroscience today, and doing so, to at least broaden our understanding of nervous functional areas and circuitry in mammals.

Fundamental questions such as the characterization of differences in the motor cortex cytoarchitecture and pathway in perissodactyls like the horse, which walks on one toenail, and mammals using a five-fingered hand like apes call for a complex answer.

Horses have undergone an extreme and relatively well documented evolutionary specialization of the distal limb, reduced to a major metacarpal bone and a single toe enclosed in the hoof. The nervous motor control of this one-fingered hand has never been studied in detail, as there is no modern neuroanatomy of ungulates (including mammals with even and odd fingers) [5], although horses possesses a relatively large brain of approx. 600 g with considerable cortical folding, details on the organization of its cortex have received little to no attention.

Although it is of significant interest, the precise organization and wiring of the auditory cortex in cetaceans, living fully underwater, is still lacking, despite the considerable interest drawn by these mammals. Previous pioneering work roughly mapped an extended auditory neocortical field in some cetaceans and their developed auditory pathway pertaining to echolocation. However, the general topography of the cetacean brain remains widely unknown.

Furthermore, the swine, a common terrestrial mammal, shows remarkable specializations in the sensorimotor development of the snout area. Recently used in cutting-edge research [6], the pig is a potent neuroanatomical model [7,8], with known complex social organization.

Knowledge on the neuroanatomic variations among mammalian species could help neuroscientists and neuropathologists in defining the relevance of the structural modifications of such findings and the possible significance of similar changes in humans.

Accordingly, there has been increasing attention brought onto the development of new animal models to understand the anatomical and genetic basis of neurodegenerative disorders [9], for which the domestic, fairly standardized Bos taurus could be a proper candidate [10]. Their gestation period (41 weeks) is comparable to the human pregnancy (38–40 weeks), and their brain is large and highly convoluted [11]. Critically, bovine frequently show naturally occurring intersex calves, also called freemartin syndrome, which could be used to study sex dimorphism in the brain [12,13].

Other models exist, such as the sheep for Huntington’s disease [14], and the bovine for transmissible spongiform encephalopathies [15].

Practically, the use of brain tissue samples from domestic mammals as translational models for neuroanatomical studies has further advantages granted by their size, including imaging and sampling. They are finally cheaply and easily obtained in large quantities from local slaughterhouses, allowing a reduction in the sacrifice of laboratory animals.

Consequently, for all of the above reasons, and to promote the use of alternative domestic (and wild) mammalian species in neuroanatomy, we propose here a fresh view on the current state of research in the field.

References

1. Manger, P.R.; Cort, J.; Ebrahim, N.; Goodman, A.; Henning, J.; Karolia, M.; Rodrigues, S.-L.; Štrkalj, G. Is 21st Century Neuroscience too Focussed on the Rat/Mouse Model of Brain Function and Dysfunction? Neuroanat. 2008, 2, doi:10.3389/neuro.05.005.2008.
2. Bolker, J. There’s more to life than rats and flies. Cell Biol. 2012, 491, 31–33, doi:10.1038/491031a.
3. Keifer, J.; Summers, C.H. Putting the “Biology” Back into “Neurobiology”: The Strength of Diversity in Animal Model Systems for Neuroscience Research. Syst. Neurosci. 2016, 10, 69, doi:10.3389/fnsys.2016.00069.
4. Bailey, J. Does the Stress of Laboratory Life and Experimentation on Animals Adversely Affect Research Data? A Critical Review. Lab. Anim. 2018, 46, 291–305, doi:10.1177/026119291804600501.
5. Voogd, J. Mammals—Introduction; In The Central Nervous System of Vertebrates, eds. R. Nieuwenhuys, H. J. Ten Donkelaar, and C. Nicholson; Springer: Berlin, Heidelberg, Germany, 1998; pp. 1637–2098.
6. Vrselja, Z.; Daniele, S. G.; Silbereis, J.; Talpo, F.; Morozov, Y. M.; Sousa, A. M. M., et al. Restoration of brain circulation and cellular functions hours post-mortem. Nature 2019, 568, 336–343. doi:10.1038/s41586-019-1099-1.
7. Watanabeab, H.; Andersena, F.; Simonsen, C.Z.; Evans, S.M.; Gjeddea, A.; Cumming, P. MR-Based Statistical Atlas of the Göttingen Minipig Brain. NeuroImage 2001, 14, 1089–1096, doi:10.1006/nimg.2001.0910.
8. Jelsing, J.; Hay-Schmidt, A.; Dyrby, T.; Hemmingsen, R.; Uylings, H.B.; Pakkenberg, B. The prefrontal cortex in the Göttingen minipig brain defined by neural projection criteria and cytoarchitecture. Brain Res. Bull. 2006, 70, 322–336, doi:10.1016/j.brainresbull.2006.06.009.
9. Mcgonigle, P.; Ruggeri, B. Animal models of human disease: Challenges in enabling translation. Pharmacol. 2014, 87, 162–171, doi:10.1016/j.bcp.2013.08.006.
10. Peruffo, A.; Cozzi, B. Bovine Brain: An in vitro Translational Model in Developmental Neuroscience and Neurodegenerative Research. Pediatr. 2014, 2, 74, doi:10.3389/fped.2014.00074.
11. Ballarin, C.; Povinelli, M.; Granato, A.; Panin, M.; Corain, L.; Peruffo, A., et al. The brain of the domestic Bos taurus: Weight, encephalization and cerebellar quotients, and comparison with other domestic and wild Cetartiodactyla. PLoS One 2016, 11. doi:10.1371/journal.pone.0154580.
12. Graïc, J.; Corain, L.; Peruffo, A.; Cozzi, B.; Swaab, D.F. The bovine anterior hypothalamus: Characterization of the vasopressin-oxytocin containing nucleus and changes in relation to sexual differentiation. Comp. Neurol. 2018, 526, 2898–2917, doi:10.1002/cne.24542.
13. Corain, L.; Grisan, E.; Graïc, J.-M.; Carvajal-Schiaffino, R.; Cozzi, B.; Peruffo, A. Multi-aspect testing and ranking inference to quantify dimorphism in the cytoarchitecture of cerebellum of male, female and intersex individuals: a model applied to bovine brains. Brain Struct. Funct. 2020, 225, 2669–2688, doi:10.1007/s00429-020-02147-x.
14. Morton, A.J. Large-Brained Animal Models of Huntington’s Disease: Sheep. Bacteriophages 2018, 1780, 221–239, doi:10.1007/978-1-4939-7825-0_12.
15. Asher, D.M.; Gregori, L. Human transmissible spongiform encephalopathies: historic view. Clin. Neurol. 2018, 153, 1–17, doi:10.1016/b978-0-444-63945-5.00001-5.

Prof. Antonella Peruffo
Dr. Jean Marie Graïc
Guest Editors

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