Identifying reliable traits across laboratory mouse exploration arenas: A meta-analysis

This study is a meta-analysis of 367 mice from a collection of behaviour neuroscience and behaviour genetic studies run in the same lab in Zurich, Switzerland. We employed correlation-based statistics to confirm and quantify consistencies in behaviour across the testing environments. All 367 mice ran exactly the same behavioural arenas: the light/dark box, the null maze, the open field arena, an emergence task and finally an object exploration task. We analysed consistency of three movement types across those arenas (resting, scanning, progressing), and their relative preference for three zones of the arenas (home, transition, exploration). Results were that 5/6 measures showed strong individual-differences consistency across the tests. Mean inter-arena correlations for these five measures ranged from +.12 to +.53. Unrotated principal component factor analysis (UPCFA) and Cronbach’s alpha measures showed these traits to be reliable and substantial (32-63% of variance across the five arenas). UPCFA loadings then indicate which tasks give the best information about these cross-task traits. One measure (that of time spent in “intermediate” zones) was not reliable across arenas. Conclusions centre on the use of individual differences research and behavioural batteries to revise understandings of what measures in one task predict for behaviour in others. Developing better behaviour measures also makes sound scientific and ethical sense

Behavior is movement only but how to interpret it? Problems and pitfalls in translational neuroscience-a 40-year experience

Translational research in behavioral neuroscience seeks causes and remedies for human mental health problems in animals, following leads imposed by clinical research in psychiatry. This endeavor faces several problems because scientists must read and interpret animal movements to represent human perceptions, mood, and memory processes. Yet, it is still not known how mammalian brains bundle all these processes into a highly compressed motor output in the brain stem and spinal cord, but without that knowledge, translational research remains aimless. Based on some four decades of experience in the field, the article identifies sources of interpretation problems and illustrates typical translational pitfalls. (1) The sensory world of mice is different. Smell, hearing, and tactile whisker sensations dominate in rodents, while visual input is comparatively small. In humans, the relations are reversed. (2) Mouse and human brains are equated inappropriately: the association cortex makes up a large portion of the human neocortex, while it is relatively small in rodents. The predominant associative cortex in rodents is the hippocampus itself, orchestrating chiefly inputs from secondary sensorimotor areas and generating species-typical motor patterns that are not easily reconciled with putative human hippocampal functions. (3) Translational interpretation of studies of memory or emotionality often neglects the ecology of mice, an extremely small species surviving by freezing or flight reactions that do not need much cognitive processing. (4) Further misinterpretations arise from confounding neuronal properties with system properties, and from rigid mechanistic thinking unaware that many experimentally induced changes in the brain do partially reflect unpredictable compensatory plasticity. (5) Based on observing hippocampal lesion effects in mice indoors and outdoors, the article offers a simplistic general model of hippocampal functions in relation to hypothalamic input and output, placing hypothalamus and the supraspinal motor system at the top of a cerebral hierarchy. (6) Many translational problems could be avoided by inclusion of simple species-typical behaviors as end-points comparable to human cognitive or executive processing, and to rely more on artificial intelligence for recognizing patterns not classifiable by traditional psychological concepts

No effect of running and laboratory housing on adult hippocampal neurogenesis in wild caught long-tailed wood mouse

BACKGROUND: Studies of adult hippocampal neurogenesis (AHN) in laboratory rodents have raised hopes for therapeutic interventions in neurodegenerative diseases and mood disorders, as AHN can be modulated by physical exercise, stress and environmental changes in these animals. Since it is not known whether cell proliferation and neurogenesis in wild living mice can be experimentally changed, this study investigates the responsiveness of AHN to voluntary running and to environmental change in wild caught long-tailed wood mice (Apodemus sylvaticus). RESULTS: Statistical analyses show that running had no impact on cell proliferation (p = 0.44), neurogenesis (p = 0.94) or survival of newly born neurons (p = 0.58). Likewise, housing in the laboratory has no effect on AHN. In addition, interindividual differences in the level of neurogenesis are not related to interindividual differences of running wheel performance (rs = -0.09, p = 0.79). There is a correlation between the number of proliferating cells and the number of cells of neuronal lineage (rs = 0.63, p < 0.001) and the number of pyknotic cells (rs = 0.5, p = 0.009), respectively. CONCLUSION: Plasticity of adult neurogenesis is an established feature in strains of house mice and brown rats. Here, we demonstrate that voluntary running and environmental changes which are effective in house mice and brown rats cannot influence AHN in long-tailed wood mice. This indicates that in wild long-tailed wood mice different regulatory mechanisms act on cell proliferation and neurogenesis. If this difference reflects a species-specific adaptation or a broader adaptive strategy to a natural vs. domestic environment is unknown

Absent or Low Rate of Adult Neurogenesis in the Hippocampus of Bats (Chiroptera)

Bats are the only flying mammals and have well developed navigation abilities for 3D-space. Even bats with comparatively small home ranges cover much larger territories than rodents, and long-distance migration by some species is unique among small mammals. Adult proliferation of neurons, i.e., adult neurogenesis, in the dentate gyrus of rodents is thought to play an important role in spatial memory and learning, as indicated by lesion studies and recordings of neurons active during spatial behavior. Assuming a role of adult neurogenesis in hippocampal function, one might expect high levels of adult neurogenesis in bats, particularly among fruit- and nectar-eating bats in need of excellent spatial working memory. The dentate gyrus of 12 tropical bat species was examined immunohistochemically, using multiple antibodies against proteins specific for proliferating cells (Ki-67, MCM2), and migrating and differentiating neurons (Doublecortin, NeuroD). Our data show a complete lack of hippocampal neurogenesis in nine of the species (Glossophaga soricina, Carollia perspicillata, Phyllostomus discolor, Nycteris macrotis, Nycteris thebaica, Hipposideros cyclops, Neoromicia rendalli, Pipistrellus guineensis, and Scotophilus leucogaster), while it was present at low levels in three species (Chaerephon pumila, Mops condylurus and Hipposideros caffer). Although not all antigens were recognized in all species, proliferation activity in the subventricular zone and rostral migratory stream was found in all species, confirming the appropriateness of our methods for detecting neurogenesis. The small variation of adult hippocampal neurogenesis within our sample of bats showed no indication of a correlation with phylogenetic relationship, foraging strategy, type of hunting habitat or diet. Our data indicate that the widely accepted notion of adult neurogenesis supporting spatial abilities needs to be considered carefully. Given their astonishing longevity, certain bat species may be useful subjects to compare adult neurogenesis with other long-living species, such as monkeys and humans, showing low rates of adult hippocampal neurogenesis

The entorhinal cortex of the Megachiroptera: a comparative study of Wahlberg's epauletted fruit bat and the straw-coloured fruit bat

This study describes the organisation of the entorhinal cortex of the Megachiroptera, straw-coloured fruit bat and Wahlberg's epauletted fruit bat. Using Nissl and Timm stains, parvalbumin and SMI-32 immunohistochemistry, we identified five fields within the medial (MEA) and lateral (LEA) entorhinal areas. MEA fields E CL and E C are characterised by a poor differentiation between layers II and III, a distinct layer IV and broad, stratified layers V and VI. LEA fields E I, E R and E L are distinguished by cell clusters in layer II, a clear differentiation between layers II and III, a wide columnar layer III and a broad sublayer Va. Clustering in LEA layer II was more typical of the straw-coloured fruit bat. Timm-staining was most intense in layers Ib and II across all fields and layer III of field E R. Parvalbumin-like staining varied along a medio-lateral gradient with highest immunoreactivity in layers II and III of MEA and more lateral fields of LEA. Sparse SMI-32-like immunoreactivity was seen only in Wahlberg's epauletted fruit bat. Of the neurons in MEA layer II, ovoid stellate cells account for ~38%, polygonal stellate cells for ~8%, pyramidal cells for ~18%, oblique pyramidal cells for ~6% and other neurons of variable morphology for ~29%. Differences between bats and other species in cellular make-up and cytoarchitecture of layer II may relate to their three-dimensional habitat. Cytoarchitecture of layer V in conjunction with high encephalisation and structural changes in the hippocampus suggest similarities in efferent hippocampal→entorhinal→cortical interactions between fruit bats and primate

Automated dissection of permanent effects of hippocampal or prefrontal lesions on performance at spatial, working memory and circadian timing tasks of C57BL/6 mice in IntelliCage

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