Marmoset Brain Research Articles

Propagation of pathological \u03b1-synuclein in marmoset brain

α-Synuclein is a defining, key component of Lewy bodies and Lewy neurites in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), as well as glial cytoplasmic inclusions in multiple system atrophy (MSA). The distribution and spreading of these pathologies are closely correlated with disease progression. Recent studies have revealed that intracerebral injection of synthetic α-synuclein fibrils or pathological α-synuclein prepared from DLB or MSA brains into wild-type or transgenic animal brains induced prion-like propagation of phosphorylated α-synuclein pathology. The common marmoset is a very small primate that is expected to be a useful model of human diseases. Here, we show that intracerebral injection of synthetic α-synuclein fibrils into adult wild-type marmoset brains (caudate nucleus and/or putamen) resulted in spreading of abundant α-synuclein pathologies, which were positive for various antibodies to α-synuclein, including phospho Ser129-specific antibody, anti-ubiquitin and anti-p62 antibodies, at three months after injection. Remarkably, robust Lewy body-like inclusions were formed in tyrosine hydroxylase (TH)-positive neurons in these marmosets, strongly suggesting the retrograde spreading of abnormal α-synuclein from striatum to substantia nigra. Moreover, a significant decrease in the numbers of TH-positive neurons was observed in the injection-side of the brain, where α-synuclein inclusions were deposited. Furthermore, most of the α-synuclein inclusions were positive for 1-fluoro-2,5-bis (3-carboxy-4-hydroxystyryl) benzene (FSB) and thioflavin-S, which are dyes widely used to visualize the presence of amyloid. Thus, injection of synthetic α-synuclein fibrils into brains of non-transgenic primates induced PD-like α-synuclein pathologies within only 3 months after injection. Finally, we provide evidence indicating that neurons with abnormal α-synuclein inclusions may be cleared by microglial cells. This is the first marmoset model for α-synuclein propagation. It should be helpful in studies to elucidate mechanisms of disease progression and in development and evaluation of disease-modifying drugs for α-synucleinopathies.

Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset.

Common marmosets (Callithrix jacchus) have recently gained popularity in biomedical research as models of aging research. Basically, they confer advantages from other non-human primates due to their shorter lifespan with onset of appearance of aging at 8 years. Old marmosets present some markers linked to neurodegeneration in the brain such as amyloid beta (Aβ)1-42 and Aβ1-40. However, there are no studies exploring other cellular markers associated with neurodegenerative diseases in this non-human primate. Using immunohistochemistry, we analyzed brains of male adolescent, adult, old, and aged marmosets. We observed accumulation of Aβ1-40 and Aβ1-42 in the cortex of aged subjects. Tau hyperphosphorylation was already detected in the brain of adolescent animals and increased with aging in a more fibrillary form. Microglia activation was also observed in the aging process, while a dystrophic phenotype accumulates in aged subjects. Interestingly, dystrophic microglia contained hyperphosphorylated tau, but active microglia did not. These results support previous findings regarding microglia dysfunctionality in aging and neurodegenerative diseases as Alzheimer’s disease. Further studies should explore the functional consequences of these findings to position this non-human primate as animal model of aging and neurodegeneration.

Brain/MINDS: A Japanese National Brain Project for Marmoset Neuroscience

Brain/MINDS (Brain Mapping by Integrated Neurotechnologies for Disease Studies) is a national brain project started by Japan in 2014. With the goal of developing the common marmoset as a model animal for neuroscience, the project aims to build a multiscale marmoset brain map, develop new technologies for experimentalists, create transgenic lines for brain disease modeling, and integrate translational findings from the clinical biomarker landscape. Brain/MINDS will collaborate with global brain projects to share technologies and resources.

Application of viral vectors to the study of neural connectivities and neural circuits in the marmoset brain.

ABSTRACTIt is important to study the neural connectivities and functions in primates. For this purpose, it is critical to be able to transfer genes to certain neurons in the primate brain so that we can image the neuronal signals and analyze the function of the transferred gene. Toward this end, our team has been developing gene transfer systems using viral vectors. In this review, we summarize our current achievements as follows. 1) We compared the features of gene transfer using five different AAV serotypes in combination with three different promoters, namely, CMV, mouse CaMKII (CaMKII), and human synapsin 1 (hSyn1), in the marmoset cortex with those in the mouse and macaque cortices. 2) We used target‐specific double‐infection techniques in combination with TET‐ON and TET‐OFF using lentiviral retrograde vectors for enhanced visualization of neural connections. 3) We used an AAV‐mediated gene transfer method to study the transcriptional control for amplifying fluorescent signals using the TET/TRE system in the primate neocortex. We also established systems for shRNA mediated gene targeting in a neocortical region where a gene is significantly expressed and for expressing the gene using the CMV promoter for an unexpressed neocortical area in the primate cortex using AAV vectors to understand the regulation of downstream genes. Our findings have demonstrated the feasibility of using viral vector mediated gene transfer systems for the study of primate cortical circuits using the marmoset as an animal model. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 354–372, 2017

Anatomical and functional neuroimaging in awake, behaving marmosets.

The common marmoset (Callithrix jacchus) is a small New World monkey that has gained significant recent interest in neuroscience research, not only because of its compatibility with gene editing techniques, but also due to its tremendous versatility as an experimental animal model. Neuroimaging modalities, including anatomical (MRI) and functional magnetic resonance imaging (fMRI), complemented by two-photon laser scanning microscopy and electrophysiology, have been at the forefront of unraveling the anatomical and functional organization of the marmoset brain. High-resolution anatomical MRI of the marmoset brain can be obtained with remarkable cytoarchitectonic detail. Functional MRI of the marmoset brain has been used to study various sensory systems, including somatosensory, auditory, and visual pathways, while resting-state fMRI studies have unraveled functional brain networks that bear great correspondence to those previously described in humans. Two-photon laser scanning microscopy of the marmoset brain has enabled the simultaneous recording of neuronal activity from thousands of neurons with single cell spatial resolution. In this article, we aim to review the main results obtained by our group and by our colleagues in applying neuroimaging techniques to study the marmoset brain. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 373-389, 2017.

A Sexually Dimorphic Area of the Dorsal Hypothalamus in Mice and Common Marmosets.

We found a novel sexually dimorphic area (SDA) in the dorsal hypothalamus (DH) of mice. The SDA-DH was sandwiched between 2 known male-biased sexually dimorphic nuclei, the principal nucleus of the bed nucleus of the stria terminalis and the calbindin-sexually dimorphic nucleus, and exhibited a female-biased sex difference in neuronal cell density. The density of neurons in the SDA-DH was increased in male mice by orchidectomy on the day of birth and decreased in female mice by treatment with testosterone, dihydrotestosterone, or estradiol within 5 days after birth. These findings indicate that the SDA-DH is defeminized under the influence of testicular testosterone, which acts via both directly by binding to the androgen receptor, and indirectly by binding to the estrogen receptor after aromatization. We measured the activity of SDA-DH neurons with c-Fos, a neuronal activity marker, in female mice during maternal and sexual behaviors. The number of c-Fos-expressing neurons in the SDA-DH of female mice was negatively correlated with maternal behavior performance. However, the number of c-Fos-expressing neurons did not change during female sexual behavior. These findings suggest that the SDA-DH contains a neuronal cell population, the activity of which decreases in females exhibiting higher performance of maternal behavior, but it may contribute less to female sexual behavior. Additionally, we examined the brain of common marmosets and found an area that appears to be homologous with the mouse SDA-DH. The sexually dimorphic structure identified in this study is not specific to mice and may be found in other species.

Viral Vector-Based Dissection of Marmoset GFAP Promoter in Mouse and Marmoset Brains.

Adeno-associated virus (AAV) vectors are small in diameter, diffuse easily in the brain, and represent a highly efficient means by which to transfer a transgene to the brain of a large animal. A major demerit of AAV vectors is their limited accommodation capacity for transgenes. Thus, a compact promoter is useful when delivering large transgenes via AAV vectors. In the present study, we aimed to identify the shortest astrocyte-specific GFAP promoter region that could be used for AAV-vector-mediated transgene expression in the marmoset brain. The 2.0-kb promoter region upstream of the GFAP gene was cloned from the marmoset genome, and short promoters (1.6 kb, 1.4 kb, 0.6 kb, 0.3 kb and 0.2 kb) were obtained by progressively deleting the original 2.0-kb promoter from the 5’ end. The short promoters were screened in the mouse cerebellum in terms of their strength and astrocyte specificity. We found that the 0.3-kb promoter maintained 40% of the strength of the original 2.0-kb promoter, and approximately 90% of its astrocyte specificity. These properties were superior to those of the 1.4-kb, 0.6-kb (20% promoter strength) and 0.2-kb (70% astrocyte specificity) promoters. Then, we verified whether the 0.3-kb GFAP promoter retained astrocyte specificity in the marmoset cerebral cortex. Injection of viral vectors carrying the 0.3-kb marmoset GFAP promoter specifically transduced astrocytes in both the cerebral cortex and cerebellar cortex of the marmoset. These results suggest that the compact 0.3-kb promoter region serves as an astrocyte-specific promoter in the marmoset brain, which permits us to express a large gene by AAV vectors that have a limited accommodation capacity.

SHARAKU: an algorithm for aligning and clustering read mapping profiles of deep sequencing in non-coding RNA processing.

Motivation: Deep sequencing of the transcripts of regulatory non-coding RNA generates footprints of post-transcriptional processes. After obtaining sequence reads, the short reads are mapped to a reference genome, and specific mapping patterns can be detected called read mapping profiles, which are distinct from random non-functional degradation patterns. These patterns reflect the maturation processes that lead to the production of shorter RNA sequences. Recent next-generation sequencing studies have revealed not only the typical maturation process of miRNAs but also the various processing mechanisms of small RNAs derived from tRNAs and snoRNAs.Results: We developed an algorithm termed SHARAKU to align two read mapping profiles of next-generation sequencing outputs for non-coding RNAs. In contrast with previous work, SHARAKU incorporates the primary and secondary sequence structures into an alignment of read mapping profiles to allow for the detection of common processing patterns. Using a benchmark simulated dataset, SHARAKU exhibited superior performance to previous methods for correctly clustering the read mapping profiles with respect to 5′-end processing and 3′-end processing from degradation patterns and in detecting similar processing patterns in deriving the shorter RNAs. Further, using experimental data of small RNA sequencing for the common marmoset brain, SHARAKU succeeded in identifying the significant clusters of read mapping profiles for similar processing patterns of small derived RNA families expressed in the brain.Availability and Implementation: The source code of our program SHARAKU is available at http://www.dna.bio.keio.ac.jp/sharaku/, and the simulated dataset used in this work is available at the same link. Accession code: The sequence data from the whole RNA transcripts in the hippocampus of the left brain used in this work is available from the DNA DataBank of Japan (DDBJ) Sequence Read Archive (DRA) under the accession number DRA004502.Contact: yasu@bio.keio.ac.jpSupplementary information: Supplementary data are available at Bioinformatics online.

Nuclear organization of the substantia nigra, ventral tegmental area and retrorubral field of the common marmoset (Callithrix jacchus): A cytoarchitectonic and TH-immunohistochemistry study

It is widely known that the catecholamine group is formed by dopamine, noradrenaline and adrenaline. Its synthesis is regulated by the enzyme called tyrosine hydroxylase. 3-hydroxytyramine/dopamine (DA) is a precursor of noradrenaline and adrenaline synthesis and acts as a neurotransmitter in the central nervous system. The three main nuclei, being the retrorubral field (A8 group), the substantia nigra pars compacta (A9 group) and the ventral tegmental area (A10 group), are arranged in the die-mesencephalic portion and are involved in three complex circuitries – the mesostriatal, mesolimbic and mesocortical pathways. These pathways are involved in behavioral manifestations, motricity, learning, reward and also in pathological conditions such as Parkinson’s disease and schizophrenia. The aim of this study was to perform a morphological analysis of the A8, A9 and A10 groups in the common marmoset (Callithrix jacchus – a neotropical primate), whose morphological and functional characteristics support its suitability for use in biomedical research. Coronal sections of the marmoset brain were submitted to Nissl staining and TH-immunohistochemistry. The morphology of the neurons made it possible to subdivide the A10 group into seven distinct regions: interfascicular nucleus, raphe rostral linear nucleus and raphe caudal linear nucleus in the middle line; paranigral and parainterfascicular nucleus in the middle zone; the rostral portion of the ventral tegmental area nucleus and parabrachial pigmented nucleus located in the dorsolateral portion of the mesencephalic tegmentum. The A9 group was divided into four regions: substantia nigra compacta dorsal and ventral tiers; substantia nigra compacta lateral and medial clusters. No subdivisions were made for the A8 group. These results reveal that A8, A9 and A10 are phylogenetically stable across species. As such, further studies concerning such divisions are necessary in order to evaluate the occurrence of subdivisions that express DA in other primate species, with the aim of characterizing its functional relevance.

Towards a comprehensive atlas of cortical connections in a primate brain: Mapping tracer injection studies of the common marmoset into a reference digital template.

The marmoset is an emerging animal model for large‐scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for coregistration of retrograde tracing data on connections of cortical areas into a 3D marmoset brain template, generated from Nissl‐stained sections. The procedure results in a series of spatial transformations that are applied to the coordinates of labeled neurons in the different cases, bringing them into common stereotaxic space. We applied this procedure to 17 injections, placed in the frontal lobe of nine marmosets as part of earlier studies. Visualizations of cortical patterns of connections revealed by these injections are supplied as Supplementary Materials. Comparison between the results of the automated and human‐based processing of these cases reveals that the centers of injection sites can be reconstructed, on average, to within 0.6 mm of coordinates estimated by an experienced neuroanatomist. Moreover, cell counts obtained in different areas by the automated approach are highly correlated (r = 0.83) with those obtained by an expert, who examined in detail histological sections for each individual. The present procedure enables comparison and visualization of large datasets, which in turn opens the way for integration and analysis of results from many animals. Its versatility, including applicability to archival materials, may reduce the number of additional experiments required to produce the first detailed cortical connectome of a primate brain. J. Comp. Neurol. 524:2161–2181, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Towards a comprehensive atlas of cortical connections in a primate brain: Mapping tracer injection studies of the common marmoset into a reference digital template

The marmoset is an emerging animal model for large‐scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for coregistration of retrograde tracing data on connections of cortical areas into a 3D marmoset brain template, generated from Nissl‐stained sections. The procedure results in a series of spatial transformations that are applied to the coordinates of labeled neurons in the different cases, bringing them into common stereotaxic space. We applied this procedure to 17 injections, placed in the frontal lobe of nine marmosets as part of earlier studies. Visualizations of cortical patterns of connections revealed by these injections are supplied as Supplementary Materials. Comparison between the results of the automated and human‐based processing of these cases reveals that the centers of injection sites can be reconstructed, on average, to within 0.6 mm of coordinates estimated by an experienced neuroanatomist. Moreover, cell counts obtained in different areas by the automated approach are highly correlated (r = 0.83) with those obtained by an expert, who examined in detail histological sections for each individual. The present procedure enables comparison and visualization of large datasets, which in turn opens the way for integration and analysis of results from many animals. Its versatility, including applicability to archival materials, may reduce the number of additional experiments required to produce the first detailed cortical connectome of a primate brain. J. Comp. Neurol. 524:2161–2181, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

In situ hybridization analyses of claustrum-enriched genes in marmosets.

The claustrum/endopiriform nucleus is a unique structure that sits between the striatum and the cerebral cortex. Recent genome-wide mapping of gene expression in mice identified various genes concentrated in this structure, suggesting a requirement for a special set of genes for its function. In situ hybridization histochemistry was performed for such "claustrum-enriched" genes in the marmoset brain. In marmosets, nurr1 and netrinG2 genes exhibited highly concentrated expression in the claustrum and endopiriform nucleus, as well as in a subpopulation of layer 6 neurons across the entire cortex, consistent with their expression patterns as described in macaques. Cux2 showed enriched expression in the upper layers (layers 2-4) and the claustrum/endopiriform nucleus. GNG2 was expressed strongly in the claustrum/endopiriform nucleus, but was abundant across cortical areas in a ventral high-dorsal low gradient. Latexin was detected in the claustrum and dorsal endopiriform nucleus, but not in cortical regions. GNB4 and Tmem163 genes were both concentrated in the claustrum/endopiriform nucleus, as reported in mice, but their cortical expression in the marmoset differed from the mouse pattern. Thus, the gene set required for the claustrum appears to be broadly conserved across species, despite various differences that suggest species-specific differentiation of brain architecture. J. Comp. Neurol. 525:1442-1458, 2017. © 2016 Wiley Periodicals, Inc.

Functional Connectivity Hubs and Networks in the Awake Marmoset Brain.

In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to a better understanding of the network organization of the brain. Increasing evidence suggests that this architecture may incorporate highly functionally connected nodes, or “hubs”, and we have recently proposed local functional connectivity density (lFCD) mapping to identify highly-connected nodes in the human brain. Here, we imaged awake nonhuman primates to test whether, like the human brain, the marmoset brain contains FC hubs. Ten adult common marmosets (Callithrix jacchus) were acclimated to mild, comfortable restraint using individualized helmets. Following restraint training, resting BOLD data were acquired during eight consecutive 10 min scans for each subject. lFCD revealed prominent cortical and subcortical hubs of connectivity across the marmoset brain; specifically, in primary and secondary visual cortices (V1/V2), higher-order visual association areas (A19M/V6[DM]), posterior parietal and posterior cingulate areas (PGM and A23b/A31), thalamus, dorsal and ventral striatal areas (caudate, putamen, lateral septal nucleus, and anterior cingulate cortex (A24a). lFCD hubs were highly connected to widespread areas of the brain, and further revealed significant network-network interactions. These data provide a baseline platform for future investigations in a nonhuman primate model of the brain’s network topology.

In situ hybridization study of CYP2D mRNA in the common marmoset brain.

The common marmoset is a non-human primate that has increasingly employed in the biomedical research including the fields of neuroscience and behavioral studies. Cytochrome P450 (CYP) 2D has been speculated to be involved in psycho-neurologic actions in the human brain. In the present study, to clarify the role of CYP2D in the marmoset brain, we investigated the expression patterns of CYP2D mRNA in the brain using in situ hybridization (ISH). In addition, to identify the gene location of CYP2D19, a well-studied CYP2D isoform in the common marmoset, a fluorescence in situ hybridization (FISH) study was performed. Consistent with findings for the human brain, CYP2D mRNA was localized in the neuronal cells of different brain regions; e.g., the cerebral cortex, hippocampus, substantia nigra, and cerebellum. FISH analysis showed that the CYP2D19 gene was located on chromosome 1q, which is homologous to human chromosome 22 on which the CYP2D6 gene exists. These results suggest that CYP2D in the marmoset brain may play the same role as human CYP2D6 in terms of brain actions, and that the CYP2D19 gene is conserved in a syntenic manner. Taken together, these findings suggest that the common marmoset is a useful model for studying psychiatric disorders related to CYP2D dysfunction in the brain.

Elevated Expression of the Cerebrospinal Fluid Disease Markers Chromogranin A and Clusterin in Astrocytes of Multiple Sclerosis White Matter Lesions.

Using proteomics, we previously identified chromogranin A (CgA) and clusterin (CLU) as disease-related proteins in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). CgA and CLU are involved in cell survival and are implicated in neurodegenerative disorders and may also have roles in MS pathophysiology. We investigated CgA and CLU expression in lesions and nonlesional regions in postmortem brains of MS patients and controls and in the brains of marmosets with experimental autoimmune encephalomyelitis. By quantitative PCR, mRNA levels of CgA and CLU were elevated in white matter but not in grey matter of MS patients. In situ analyses showed greater expression of CgA and CLU in white matter lesions than in normal-appearing regions in MS patients and in the marmosets, primarily in or adjacent to perivascular spaces and inflammatory infiltrates. Both proteins were expressed by glial fibrillary acidic protein-positive astrocytes. CgA was more localized in astrocytic processes and endfeet surrounding blood vessels and was abundant in the superficial glia limitans and ependyma, 2 CSF-brain borders. Increased expression of CgA and CLU in reactive astrocytes in MS white matter lesions supports a role for these molecules as neuro-inflammatory mediators and their potential as CSF markers of active pathological processes in MS patients.

α-Synuclein aggregation in the olfactory bulb of middle-aged common marmoset

The synaptic protein α-synuclein has been identified as a major component of Lewy bodies, a pathological hallmark of Parkinson's disease (PD). Prior to the formation of Lewy bodies, mislocalization and aggregation of the α-synuclein in brain tissue is frequently observed in various neurodegenerative diseases. Aberrant accumulation and localization of α-synuclein are also observed in the aging human brain, for which reason aging is regarded as a risk factor for neurodegenerative disease. To investigate changes in α-synuclein properties in the aging brain, we compared α-synuclein immunoreactivity in brain tissue of young (2-years-old) and middle-aged (6-years-old) common marmoset (Callithrix jacchus). Our analyses revealed marked changes in α-synuclein immunoreactivity in the olfactory bulb of common marmosets of these age cohorts. Perikaryal α-synuclein aggregations were formed in the olfactory bulb in middle-aged animals. We also observed signals of α-synuclein accumulation in hippocampus in this cohort; however, unlike in the olfactory bulb, hippocampal α-synuclein signals were localized in the synaptic terminals. We did not observe either of these features in younger marmosets, which suggest that aging may play a role in these phenomena.Our results using common marmoset brain corresponded with the observation that the α-synuclein aggregations were first occurred from olfactory bulb in human normal aged and PD brain. Therefore, common marmoset is expected as useful model for α-synuclein pathology.

Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets

BackgroundMRI has the advantage of sampling large areas of tissue and locating areas of interest in 3D space in both living and ex vivo systems, whereas histology has the ability to examine thin slices of ex vivo tissue with high detail and specificity. Although both are valuable tools, it is currently difficult to make high-precision comparisons between MRI and histology due to large differences inherent to the techniques. A method combining the advantages would be an asset to understanding the pathological correlates of MRI. New method3D-printed brain holders were used to maintain marmoset brains in the same orientation during acquisition of ex vivo MRI and pathologic cutting of the tissue. ResultsThe results of maintaining this same orientation show that sub-millimeter, discrete neuropathological features in marmoset brain consistently share size, shape, and location between histology and ex vivo MRI, which facilitates comparison with serial imaging acquired in vivo. Comparison with existing methodsExisting methods use computational approaches sensitive to data input in order to warp histologic images to match large-scale features on MRI, but the new method requires no warping of images, due to a preregistration accomplished in the technique, and is insensitive to data formatting and artifacts in both MRI and histology. ConclusionsThe simple method of using 3D-printed brain holders to match brain orientation during pathologic sectioning and MRI acquisition enables rapid and precise comparison of small features seen on MRI to their underlying histology.

Striatal and extrastriatal dopamine release in the common marmoset brain measured by positron emission tomography and [(18)F]fallypride.

Previous studies have demonstrated that patients with schizophrenia show greater sensitivity to psychostimulants than healthy subjects. Sensitization to psychostimulants and resultant alteration of dopaminergic neurotransmission in rodents has been suggested as a useful model of schizophrenia. This study sought to examine the use of methylphenidate as a psychostimulant to induce dopamine release and that of [(18)F]fallypride as a radioligand to quantify the release in a primate model of schizophrenia. Four common marmosets were scanned by positron emission tomography twice, before and after methylphenidate challenge, to evaluate dopamine release. Four other marmosets were sensitized by repeated methamphetamine (MAP) administration. Then, they were scanned twice, before and after methylphenidate challenge, to evaluate whether MAP-sensitization induced greater sensitivity to methylphenidate. We revealed a main effect of the methylphenidate challenge but not the MAP pretreatment on the striatal binding potential. These results suggest that methylphenidate-induced striatal dopamine release in the common marmoset could be evaluated by [(18)F]fallypride.

Functional MRI of visual responses in the awake, behaving marmoset

The visual brain is composed of interconnected subcortical and cortical structures that receive and process image information originating in the retina. The visual system of nonhuman primates, in particular macaques, has been studied in great detail in order to elucidate principles of human sensation and perception. The common marmoset (Callithrix jacchus) is a small New World monkey of growing interest as a primate model for neuroscience. Marmosets have advantages over macaques because of their small size, lissencephalic cortex, and growing potential for viral and genetic manipulations. Previous anatomical studies and electrophysiological recordings in anesthetized marmosets have shown that this species’ cortical visual hierarchy closely resembles that of other primates, including humans. Until now, however, there have been no attempts to systematically study visual responses throughout the marmoset brain using fMRI. Here we show that awake marmosets readily learn to carry out a simple visual task inside the bore of an MRI scanner during functional mapping experiments. Functional scanning at 500μm in-plane resolution in a 30cm horizontal bore at 7T revealed robust positive blood oxygenation level-dependent (BOLD) fMRI responses to visual stimuli throughout visual cortex and associated subcortical areas. Nonvisual sensory areas showed negative contrasts to visual stimuli compared to the fixation dot only baseline. Structured images of objects and faces led to stronger responses than scrambled control images at stages beyond early visual cortex. Our study establishes fMRI mapping of visual responses in awake, behaving marmosets as a straightforward and valuable tool for assessing the functional organization of the primate brain at high resolution.

Complex and dynamic expression of cadherins in the embryonic marmoset cerebral cortex.

Cadherin is a cell adhesion molecule widely expressed in the nervous system. Previously, we analyzed the expression of nine classic cadherins (Cdh4, Cdh6, Cdh7, Cdh8, Cdh9, Cdh10, Cdh11, Cdh12, and Cdh20) and T‐cadherin (Cdh13) in the developing postnatal common marmoset (Callithrix jacchus) brain, and found differential expressions between mice and marmosets. In this study, to explore primate‐specific cadherin expression at the embryonic stage, we extensively analyzed the expression of these cadherins in the developing embryonic marmoset brain. Each cadherin showed differential spatial and temporal expression and exhibited temporally complicated expression. Furthermore, the expression of some cadherins differed from that in rodent brains, even at the embryonic stage. These results suggest the possibility that the differential expressions of diverse cadherins are involved in primate specific cortical development, from the prenatal to postnatal period.