Significance It is widely recognized that studying the detailed anatomy of the human brain is of great importance for neuroscience and medicine. The principal means for achieving this goal is ...presently diffusion magnetic resonance imaging (dMRI) tractography, which uses the local diffusion of water throughout the brain to estimate the course of long-range anatomical projections. Such projections connect gray matter regions through axons that travel in the deep white matter. The present study combines dMRI tractography with histological analysis to investigate where in the brain this method succeeds and fails. We conclude that certain superficial white matter systems pose challenges for measuring cortical connections that must be overcome for accurate determination of detailed neuroanatomy in humans.
In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure–function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that ∼50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately.
The common marmoset (Callithrix jacchus) has garnered interest recently as a powerful model for the future of neuroscience research. Much of this excitement has centered on the species’ reproductive ...biology and compatibility with gene editing techniques, which together have provided a path for transgenic marmosets to contribute to the study of disease as well as basic brain mechanisms. In step with technical advances is the need to establish experimental paradigms that optimally tap into the marmosets’ behavioral and cognitive capacities. While conditioned task performance of a marmoset can compare unfavorably with rhesus monkey performance on conventional testing paradigms, marmosets’ social behavior and cognition are more similar to that of humans. For example, marmosets are among only a handful of primates that, like humans, routinely pair bond and care cooperatively for their young. They are also notably pro-social and exhibit social cognitive abilities, such as imitation, that are rare outside of the Apes. In this Primer, we describe key facets of marmoset natural social behavior and demonstrate that emerging behavioral paradigms are well suited to isolate components of marmoset cognition that are highly relevant to humans. These approaches generally embrace natural behavior, which has been rare in conventional primate testing, and thus allow for a new consideration of neural mechanisms underlying primate social cognition and signaling. We anticipate that through parallel technical and paradigmatic advances, marmosets will become an essential model of human social behavior, including its dysfunction in neuropsychiatric disorders.
•Marmosets offer novel avenues to study the intricacies of the primate social brain•Humans and marmosets share notable similarities in aspects of their sociality•The challenges of the primate social landscape has shaped primate brain evolution•Active social paradigms in marmosets lend unique insight into social brain function
The marmoset is an emerging model organism in the Neurosciences. Miller et al. discuss the advantages of this species as a model of human social brain function and dysfunction. Several characteristics of human and marmoset social behavior, cognition, and communication have several notable similarities, while their brains share the core primate architecture. By taking advantage of the species’ suitability for freely moving neural recording techniques, as well as active social experimental paradigms, research in marmosets is beginning to broaden our knowledge of primate social brain function.
Research with non‐human primates (NHP) has been essential and effective in increasing our ability to find cures for a large number of diseases that cause human suffering and death. Extending the ...availability and use of genetic engineering techniques to NHP will allow the creation and study of NHP models of human disease, as well as broaden our understanding of neural circuits in the primate brain. With the recent development of efficient genetic engineering techniques that can be used for NHP, there's increased hope that NHP will significantly accelerate our understanding of the etiology of human neurological and neuropsychiatric disorders. In this article, we review the present state of genetic engineering tools used in NHP, from the early efforts to induce exogeneous gene expression in macaques and marmosets, to the latest results in producing germline transmission of different transgenes and the establishment of knockout lines of specific genes. We conclude with future perspectives on the further development and employment of these tools to generate genetically engineered NHP.
(i) Non‐human primates (NHP) models are essential in biomedical research; (ii) genetically engineered NHP are essential for human genetic disorders; (iii) this article reviews the present state of genetic engineering in NHP.
Approaches to generate genetically engineered non‐human primates.
Brains, genes, and primates Izpisua Belmonte, Juan Carlos; Callaway, Edward M; Caddick, Sarah J ...
Neuron (Cambridge, Mass.),
05/2015, Letnik:
86, Številka:
3
Journal Article
Recenzirano
Odprti dostop
One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated ...expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators, and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive, and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward.
Abstract
Curiosity is a fundamental nature of animals for adapting to changing environments, but its underlying brain circuits and mechanisms remain poorly understood. One main barrier is that ...existing studies use rewards to train animals and motivate their engagement in behavioral tasks. As such, the rewards become significant confounders in interpreting curiosity. Here, we overcame this problem by studying research-naïve and naturally curious marmosets that can proactively and persistently participate in a visual choice task without external rewards. When performing the task, the marmosets manifested a strong innate preference towards acquiring new information, associated with faster behavioral responses. Longitudinally functional magnetic resonance imaging revealed behavior-relevant brain states that reflected choice preferences and engaged several brain regions, including the cerebellum, the hippocampus, and cortical areas 19DI, 25, and 46D, with the cerebellum being the most prominent. These results unveil the essential brain circuits and dynamics underlying curiosity-driven activity.
The common marmoset (Callithrix jacchus) is a New-World monkey of growing interest in neuroscience. Magnetic resonance imaging (MRI) is an essential tool to unveil the anatomical and functional ...organization of the marmoset brain. To facilitate identification of regions of interest, it is desirable to register MR images to an atlas of the brain. However, currently available atlases of the marmoset brain are mainly based on 2D histological data, which are difficult to apply to 3D imaging techniques. Here, we constructed a 3D digital atlas based on high-resolution ex-vivo MRI images, including magnetization transfer ratio (a T1-like contrast), T2w images, and multi-shell diffusion MRI. Based on the multi-modal MRI images, we manually delineated 54 cortical areas and 16 subcortical regions on one hemisphere of the brain (the core version). The 54 cortical areas were merged into 13 larger cortical regions according to their locations to yield a coarse version of the atlas, and also parcellated into 106 sub-regions using a connectivity-based parcellation method to produce a refined atlas. Finally, we compared the new atlas set with existing histology atlases and demonstrated its applications in connectome studies, and in resting state and stimulus-based fMRI. The atlas set has been integrated into the widely-distributed neuroimaging data analysis software AFNI and SUMA, providing a readily usable multi-modal template space with multi-level anatomical labels (including labels from the Paxinos atlas) that can facilitate various neuroimaging studies of marmosets.
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•MRI-based 3D digital atlas of the marmoset brain for MRI and connectome studies.•Marmoset brain templates created from multi-modal high-resolution 3D MRI.•Anatomical regions manually delineated and labeled directly on MRI dataset.•Finer parcellation of the cortex obtained based on structural connectivity profiles.•Fully-featured atlas functions and integration with the Paxinos atlas.
The default mode network (DMN) is associated with a wide range of brain functions. In humans, the DMN is marked by strong functional connectivity among three core regions: medial prefrontal cortex ...(mPFC), posterior parietal cortex (PPC), and the medial parietal and posterior cingulate cortex (PCC). Neuroimaging studies have shown that the DMN also exists in non-human primates, suggesting that it may be a conserved feature of the primate brain. Here, we found that, in common marmosets, the dorsolateral prefrontal cortex (dlPFC; peak at A8aD) has robust fMRI functional connectivity and reciprocal anatomical connections with the posterior DMN core regions (PPC and PCC), while the mPFC has weak connections with the posterior DMN core regions. This strong dlPFC but weak mPFC connectivity in marmoset differs markedly from the stereotypical DMN in humans. The mPFC may be involved in brain functions that are further developed in humans than in other primates.
The standard anatomical brain template provides a common space and coordinate system for visualizing and analyzing neuroimaging data from large cohorts of subjects. Previous templates and atlases for ...the common marmoset brain were either based on data from a single individual or lacked essential functionalities for neuroimaging analysis. Here, we present new population-based in-vivo standard templates and tools derived from multi-modal data of 27 marmosets, including multiple types of T1w and T2w contrast images, DTI contrasts, and large field-of-view MRI and CT images. We performed multi-atlas labeling of anatomical structures on the new templates and constructed highly accurate tissue-type segmentation maps to facilitate volumetric studies. We built fully featured brain surfaces and cortical flat maps to facilitate 3D visualization and surface-based analyses, which are compatible with most surface analyzing tools, including FreeSurfer, AFNI/SUMA, and the Connectome Workbench. Analysis of the MRI and CT datasets revealed significant variations in brain shapes, sizes, and regional volumes of brain structures, highlighting substantial individual variabilities in the marmoset population. Thus, our population-based template and associated tools provide a versatile analysis platform and standard coordinate system for a wide range of MRI and connectome studies of common marmosets. These new template tools comprise version 3 of our Marmoset Brain Mapping Project and are publicly available via marmosetbrainmapping.org/v3.html.
Nests are essential constructions that determine fitness, yet their structure can vary substantially across bird species. While there is evidence supporting a link between nest architecture and the ...habitat a species occupies, we still ignore what ecological and evolutionary processes are linked to different nest types. Using information on 3175 species of songbirds, we show that—after controlling for latitude and body size—species that build domed nests (i.e. nests with a roof) have smaller ranges, are less likely to colonise urban environments and have potentially higher extinction rates compared to species with open and cavity nests. Domed nests could be a costly specialisation, and we show that these nests take more time to be built, which could restrict breeding opportunities. These diverse strands of evidence suggest that the transition from domed to open nests in passerines could represent an important evolutionary innovation behind the success of the largest bird radiation.
Nests are fundamental structures in the lives of birds, but we know little about their evolution. We collated information on nest architecture for more than 3000 species, and found that building nests without a roof (open nests) is associated with having larger geographic ranges and living in cities. These nests also take less days to construct compared to domed nests. We suggest that building open instead of domed nests could have played an important role in the ecological success of modern birds.
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