Research Article: Volumes of brain structures in captive wild-type and laboratory rats: 7T magnetic resonance in vivo automatic atlas-based study

Date Published: April 11, 2019

Publisher: Public Library of Science

Author(s): Marlena Welniak–Kaminska, Michal Fiedorowicz, Jaroslaw Orzel, Piotr Bogorodzki, Klaudia Modlinska, Rafal Stryjek, Anna Chrzanowska, Wojciech Pisula, Pawel Grieb, Grainne Mary McAlonan.


Selective breeding of laboratory rats resulted in changes of their behavior. Concomitantly, the albino strains developed vision related pathologies. These alterations certainly occurred on the background of modifications in brain morphology. The aim of the study was to assess and compare volumes of major structures in brains of wild-captive, laboratory albino and laboratory pigmented rats. High resolution T2-weighted images of brains of adult male Warsaw Wild Captive Pisula-Stryjek rats (WWCPS, a model of wild type), laboratory pigmented (Brown Norway strain, BN) and albino rats (Wistar strain, WI) were obtained with a 7T small animal-dedicated magnetic resonance tomograph. Volume quantification of whole brains and 50 brain structures within each brain were performed with the digital Schwarz rat brain atlas and a custom-made MATLAB/SPM8 scripts. Brain volumes were scaled to body mass, whereas volumes of brain structures were normalized to individual brain volumes. Normalized brain volume was similar in WWCPS and BN, but lower in WI. Normalized neocortex volume was smaller in both laboratory strains than in WWCPS and the visual cortex was smaller in albino WI rats than in WWCPS and BN. Relative volumes of phylogenetically older structures, such as hippocampus, amygdala, nucleus accumbens and olfactory nuclei, also displayed certain strain-related differences. The present data shows that selective breeding of laboratory rats markedly affected brain morphology, the neocortex being most significantly altered. In particular, albino rats display reduced volume of the visual cortex, possibly related to retinal degeneration and the development of blindness.

Partial Text

Several strains of laboratory rats are bred and supplied for use as experimental animals in multiple research fields including medicine, biology and psychology. These strains are the result of a certain type of domestication of the wild rat species, Rattus norvegicus, for which Lockhard [1] proposed 50 years ago the term “laboratorization”. Selective breeding for laboratory purposes has led to remarkable differences between laboratory rats and their wild ancestors in the morphology, physiology and behavior. As recognized by Lockhard [1], laboratorization has resulted in the elimination of numerous traits maladaptive in a laboratory environment, such as savageness and the fight and flight response, and active selection of genetic background of desired traits such as amiability, acceptance of strangers, larger litters, long reproductive periods, tolerance to loud noises, etc. Further differences between laboratory and wild rats, which have been characterized more recently, include differences in complex behaviors such as burrowing, swimming [2] and play-fighting [3, 4]. Laboratory rats learn quicker than wild rats but they also are faster in forgetting the learned reaction [5, 6]. Wild rats exhibit a significantly higher level of aggression towards other individuals of their species [7, 8], and are more responsive to changes in their environment [2, 9–11].

The tested groups of rats presented large differences in body weight: WWCPS (167.3±9.1 g), BN (182.5±7.2 g). Wistar rats had significantly higher body mass than WWCPS (292.0±10.2 g; p = 0.00003) and BN (p = 0.00008). Structural T2-weighted MR images were acquired for all the tested groups of animals (Fig 2) and were used for calculations of the brain size and volumes of the specific brain structures. Mean brain size in WWCPS was calculated to 1712±28.5 mm3. It was smaller than in BN (1832± 25.9 mm3; p = 0.01) and WI (1971±22.7 mm3, p = 0.0003). Brain volume scaled to body mass was similar in WWCPS and BN (10.24±0.17 mm3/g vs. 10.05±0.14 mm3/g; ns) but significantly lower in WI (6.75±0.22 mm3/g; p = 0.00008; Fig 3, Table 1).

In the present study we used in vivo MRI technique employing a magnetic field of 7 Tesla to collect images of brains of young adult wild-captive rats and young adult rats of two laboratory strains, albino (Wistar) and pigmented (Brown Norway). Animals were randomly selected from different families by age (8–9 weeks). In the images, using digital MRI Schwarz rat brain atlas, we segmented and quantitated 50 brain regions, and looked for differences between the strains. Fully automated MR image analysis and quantitation of structure volumes provided fast, all-encompassing and non-invasive quantitative evaluation of brain structures. In the case of rat brain poor contrast between anatomical structures makes it difficult to achieve reproducible results using manual segmentation, whereas the standardized image registration and warping methods make the segmentation process more precise and objective [25–27]. Atlas-based morphometry approach allowed to avoid operator bias, providing for faster and more accurate assessment of brain morphology. Moreover, MR imaging performed in vivo allowed assessment of the size of brain structures in their natural environment and conditions, thus avoiding post-mortem changes in shape and volume caused by the preparation or fixation of the tissue [26, 31]. The brain images were registered to the templates and atlases basing on images of a similar spatial resolution that were acquired in vivo [21, 23].

Alterations in the brain structure that might be attributed to domestication in rat do not appear homogeneously. Firstly, cortical (isocortex) structures form a definitely smaller part of the brain volume in laboratory rats, especially in Wistar, as compared to WWCPS rats. Secondly, the structures belonging to phylogenetically older layers such as: hippocampus, amygdala, accumbens nuclei, and olfactory tubercle and nuclei form a relatively bigger part of the brain volume in WI and BN rats as compared to their wild-type counterparts. These two robust effects may lead us to propose a hypothesis of the mechanism underlying both of these effects. The prolonged effect of domestication/laboratorization in BN and Wistar rats is manifested in their brain by the relative reduction of cortical volume when compared to the phylogenetically older structures. This would mean, that impoverished, laboratory environmental conditions impair mainly the most recent evolutionary advancements, such as the neocortex and its functions, whereas the more ancient structures remain relatively intact.




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