Tensor-based morphometry and stereology reveal brain pathology in the complexin1 knockout mouse.

Complexins (Cplxs) are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice (Cplx1(-/-)) have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx1(-/-) mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx1(-/-) mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1(-/-) and Cplx1(+/+) mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx1(-/-) mice when compared to Cplx1(+/+) animals. Our study is the first to describe pathological changes in Cplx1(-/-) mouse brain. We suggest that the ataxia in Cplx1(-/-) mice is likely to be due to pathological changes in both cerebellum and thalamus. Reduced levels of Cplx proteins have been reported in brains of patients with neurodegenerative diseases. Therefore, understanding the effects of Cplx depletion in brains from Cplx1(-/-) mice may also shed light on the mechanisms underlying pathophysiology in disorders in which loss of Cplx1 occurs

Anatomical transition of trilaminar cerebellar cortex between reptiles and Aves

Background: Motor coordination in vertebrates is primarily regulated by cerebellum. Divergence of aves from reptilian ancestors results in noticeable improvement in the motor coordination. This study aims to explore anatomical innovations in the cerebellar cortex during the course of evolution of reptiles and aves.Methods: Three representative species each from reptilian and avian lineages were selected to represent both vertebrate classes. Complete brain was dissected out from the cranial cavity of each specimen after radiological assessment of its extent. After gross examination, the brains were subjected to detailed histological investigation using conventional and special strains. Micrometry of layer and cellular architecture of cerebellar cortex were undertaken digitally using ImageJ and statistically compared using GraphPad Prism.Results: Grossly, significant increase (p<0.0001) in brain mass, brain volume and cerebellar volume was observed in aves compared to reptiles. Histo-morphometric analyses of granular and molecular layers of cerebellum showed statistically significant decrease (p<0.0001) in the thickness of avian representatives compared to reptilian counterparts. Similarly significant decrease (p<0.0001) in the interpurkinje neuronal distance was observed in aves compared to reptiles. Conversely, increase cellular and neuronal count (p=0.0332 to <0.0001) count was observed in all three layers of avian cerebellum in comparison to reptiles. This suggests increased cellular packaging and/or density in the avian cerebellum compared to reptiles. Conclusion: In summary, significant increase in the cellular density and differentiation in the cerebellum of avian representatives may provide anatomical basis of increased motor coordination in aves compared to reptiles.  Keywords: Cerebellum; Evolution; Granular Layer; Molecular Layer; Purkinje Laye

Substantially thinner internal granular layer and reduced molecular layer surface in the cerebellum of the Tc1 mouse model of Down Syndrome - a comprehensive morphometric analysis with active staining contrast-enhanced MRI

Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer

Shaping Diversity Into the Brain’s Form and Function

The brain contains a large diversity of unique cell types that use specific genetic programs to control development and instruct the intricate wiring of sensory, motor, and cognitive brain regions. In addition to their cellular diversity and specialized connectivity maps, each region’s dedicated function is also expressed in their characteristic gross external morphologies. The folds on the surface of the cerebral cortex and cerebellum are classic examples. But, to what extent does structure relate to function and at what spatial scale? We discuss the mechanisms that sculpt functional brain maps and external morphologies. We also contrast the cryptic structural defects in conditions such as autism spectrum disorders to the overt microcephaly after Zika infections, taking into consideration that both diseases disrupt proper cognitive development. The data indicate that dynamic processes shape all brain areas to fit into jigsaw-like patterns. The patterns in each region reflect circuit connectivity, which ultimately supports local signal processing and accomplishes multi-areal integration of information processing to optimize brain functions

Variation in Brain Morphology of Intertidal Gobies: A Comparison of Methodologies Used to Quantitatively Assess Brain Volumes in Fish

When correlating brain size and structure with behavioural and environmental characteristics, a range of techniques can be utilised. This study used gobiid fishes to quantitatively compare brain volumes obtained via three different methods; these included the commonly used techniques of histology and approximating brain volume to an idealised ellipsoid, and the recently established technique of X-ray micro-computed tomography (micro-CT). It was found that all three methods differed significantly from one another in their volume estimates for most brain lobes. The ellipsoid method was prone to over- or under-estimation of lobe size, histology caused shrinkage in the telencephalon, and although micro-CT methods generated the most reliable results, they were also the most expensive. Despite these differences, all methods depicted quantitatively similar relationships among the four different species for each brain lobe. Thus, all methods support the same conclusions that fishes inhabiting rock pool and sandy habitats have different patterns of brain organisation. In particular, fishes from spatially complex rock pool habitats were found to have larger telencephalons, while those from simple homogenous sandy shores had a larger optic tectum. Where possible we recommend that micro-CT be used in brain volume analyses, as it allows for measurements without destruction of the brain and fast identification and quantification of individual brain lobes, and minimises many of the biases resulting from the histology and ellipsoid methods

In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain

Hundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 mum. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior

Existence and Continuity of Minimizers for the Estimation of Growth Mapped Evolutions for Current Data Term and Couterexamples for Varifold Data Term

In the field of computational anatomy, the complexity of changes occurring during the evolution of a living shape while it is growing, aging or reacting to a disease, calls for more and more accurate models to allow subject comparison. Growth mapped evolutions have been introduced to tackle the loss of homology between two ages of an organism following a growth process that involves creation of new material. They model the evolution of longitudinal shape data with partial mappings. One viewpoint consists in a progressive embedding of the shape into an ambient space on which acts a group of diffeomorphisms. In practice, the shape evolves through a time-varying dynamic called the growth dynamic. The concept of shape space has now been widely studied and successfully applied to analyze the variability of a population of related shapes. Time-varying dynamics subsequently enlarge this framework and open the door to new optimal control problems for the assimilation of longitudinal shape data. We address in this paper an interesting problem in the field of the calculus of variations to investigate the existence and continuity of solutions for the registration of growth mapped evolutions with the growth dynamic. This theoretical question highlights the unexpected role of the data term grounded either on current or varifold representations. Indeed, in this new framework, the spatial regularity of a continuous scenario estimated from a temporal sequence of shapes with the growth dynamic depends on the temporal regularity of the deformation. Current metrics have the property to be more robust to this spatial regularity than varifold metrics. We will establish the existence and continuity of global minimizers for current data term and highlight two counterexamples for varifold data term

A brain and a head for a different habitat : Size variation in four morphs of Arctic charr (Salvelinus alpinus(L.)) in a deep oligotrophic lake

Adaptive radiation is the diversification of species to different ecological niches and has repeatedly occurred in different salmonid fish of postglacial lakes. In Lake Tinnsjoen, one of the largest and deepest lakes in Norway, the salmonid fish, Arctic charr (Salvelinus alpinus(L.)), has likely radiated within 9,700 years after deglaciation into ecologically and genetically segregated Piscivore, Planktivore, Dwarf, and Abyssal morphs in the pelagial, littoral, shallow-moderate profundal, and deep-profundal habitats. We compared trait variation in the size of the head, the eye and olfactory organs, as well as the volumes of five brain regions of these four Arctic charr morphs. We hypothesised that specific habitat characteristics have promoted divergent body, head, and brain sizes related to utilized depth differing in environmental constraints (e.g., light, oxygen, pressure, temperature, and food quality). The most important ecomorphological variables differentiating morphs were eye area, habitat, and number of lamellae. The Abyssal morph living in the deepest areas of the lake had the smallest brain region volumes, head, and eye size. Comparing the olfactory bulb with the optic tectum in size, it was larger in the Abyssal morph than in the Piscivore morph. The Piscivore and Planktivore morphs that use more illuminated habitats have the largest optic tectum volume, followed by the Dwarf. The observed differences in body size and sensory capacities in terms of vision and olfaction in shallow and deepwater morphs likely relates to foraging and mating habitats in Lake Tinnsjoen. Further seasonal and experimental studies of brain volume in polymorphic species are needed to test the role of plasticity and adaptive evolution behind the observed differences.Peer reviewe

A surface-based analysis of hemispheric asymmetries and folding of cerebral cortex in term-born human infants

We have established a population average surface based atlas of human cerebral cortex at term gestation and used it to compare infant and adult cortical shape characteristics. Accurate cortical surface reconstructions for each hemisphere of 12 healthy term gestation infants were generated from structural magnetic resonance imaging data using a novel segmentation algorithm. Each surface was inflated, flattened, mapped to a standard spherical configuration, and registered to a target atlas sphere that reflected shape characteristics of all 24 contributing hemispheres using landmark constrained surface registration. Population average maps of sulcal depth, depth variability, 3-dimensional positional variability, and hemispheric depth asymmetry were generated and compared to previously established maps of adult cortex. We found that cortical structure in term infants is similar to the adult in many respects, including the pattern of individual variability and the presence of statistically significant structural asymmetries in lateral temporal cortex, including the planum temporale and superior temporal sulcus. These results indicate that several features of cortical shape are minimally influenced by the postnatal environment