Afonso C Silva

Afonso C Silva
University of Pittsburgh | Pitt · Department of Neurobiology

Ph.D.

About

180
Publications
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Introduction
Afonso C Silva currently works in the Department of Neurobiology at the University of Pittsburgh

Publications

Publications (180)
Article
The common marmoset (Callithrix jacchus) is quickly gaining traction as a premier neuroscientific model. However, considerable progress is still needed in understanding the functional and structural organization of the marmoset brain to rival that documented in longstanding preclinical model species, like mice, rats, and Old World primates. To acce...
Article
Although the common marmoset (Callithrix jacchus) has been maintained in captivity in biomedical research settings for decades, interest and use of the species as an animal model for a diverse array of purposes has increased in the 21st century. Unfortunately, the development of validated animal care standards such as nutrition, husbandry, and clin...
Article
Background: There has been a growing interest in the utility of the common marmoset (Callithrix jacchus) as a model system for Alzheimer's disease (AD). As a translational model for AD, marmosets retain anatomical and functional organization of the primate brain that better aligns with humans to enable improved studies of higher order cognitive pr...
Preprint
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The comprehensive integration of structural and functional connectivity data is required for the accurate modeling of brain functions. While resources for studying structural connectivity of non-human primate marmoset brains already exist, their integration with functional connectivity data has remained unavailable. Therefore, we present a comprehe...
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Open science initiatives are creating opportunities to increase research coordination and impact in nonhuman primate (NHP) imaging. The PRIMatE Data and Resource Exchange community recently developed a collaboration-based strategic plan to advance NHP imaging as an integrative approach for multiscale neuroscience.
Preprint
Remyelination is crucial for recovery from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that re...
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The corpus callosum (CC), the anterior (AC), and the posterior (PC) commissures are the principal axonal fiber bundle pathways that allow bidirectional communication between the brain hemispheres. Here, we used the Allen mouse brain connectivity atlas and high-resolution diffusion-weighted MRI (DWI) to investigate interhemispheric fiber bundles in...
Article
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 c...
Article
Developmental malformations (dysgenesis) of the corpus callosum lead to neurological conditions with a broad range of clinical presentations. Investigating the altered brain connectivity patterns is crucial to understanding both adaptive and maladaptive neuroplasticity in corpus callosum dysgenesis patients. Here, we acquired structural diffusion-w...
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The use of the common marmoset monkey (Callithrix jacchus) for neuroscientific research has grown markedly in the last decade. Magnetic resonance imaging (MRI) has played a significant role in establishing the extent of comparability of marmoset brain architecture with the human brain and brains of other preclinical species (eg, macaques and rodent...
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The rapid adoption of marmosets in neuroscience has created a demand for three dimensional (3D) atlases of the brain of this species to facilitate data integration in a common reference space. We report on a new open access template of the marmoset cortex (the Nencki–Monash, or NM template), representing a morphological average of 20 brains of youn...
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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 p...
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The corpus callosum, the principal structural avenue for interhemispheric neuronal communication, controls the brain’s lateralization. Developmental malformations of the corpus callosum (CCD) can lead to learning and intellectual disabilities. Currently, there is no clear explanation for these symptoms. Here, we used resting-state functional MRI (r...
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Over the past 10-20 years, neuroscience witnessed an explosion in the use of non-invasive imaging methods, particularly magnetic resonance imaging (MRI), to study brain structure and function. Simultaneously, with access to MRI in many research institutions, MRI has become an indispensable tool for researchers and veterinarians to guide improvement...
Article
Cortical lesions are a primary driver of disability in multiple sclerosis (MS). However, noninvasive detection of cortical lesions with in vivo magnetic resonance imaging (MRI) remains challenging. Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a relevant animal model of MS for investigating the pathophysiological mechani...
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The primate brain contains a large number of interconnected visual areas, whose spatial organization and intracortical projections show a high level of conservation across species. One fiber pathway of recent interest is the vertical occipital fasciculus (VOF), which is thought to support communication between dorsal and ventral visual areas in the...
Preprint
Full-text available
The rapid adoption of marmosets in neuroscience has created a demand for three dimensional (3D) atlases of the brain of this species to facilitate data integration in a common reference space. We report on a new open access template of the marmoset cortex (the Nencki–Monash, or NM template), representing a morphological average of 20 brains of youn...
Article
Full-text available
Corpus callosum dysgenesis (CCD) is a developmental brain condition in which some white matter fibers fail to find their natural course across the midplane, reorganizing instead to form new aberrant pathways. This type of white matter reorganization is known as long-distance plasticity (LDP). The present work aimed to characterize the Balb/c mouse...
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Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions.
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While the fundamental importance of the white matter in supporting neuronal communication is well known, existing publications of primate brains do not feature a detailed description of its complex anatomy. The main barrier to achieving this is that existing primate neuroimaging data have insufficient spatial resolution to resolve white matter path...
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Inflammatory destruction of iron-rich myelin is characteristic of multiple sclerosis (MS). Although iron is needed for oligodendrocytes to produce myelin during development, its deposition has also been linked to neurodegeneration and inflammation, including in MS. We report perivascular iron deposition in multiple sclerosis lesions that was mirror...
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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...
Article
Background:: Experimental autoimmune encephalomyelitis (EAE) in the common marmoset is a nonhuman primate model of multiple sclerosis (MS) that shares numerous clinical, radiological, and pathological features with MS. Among the clinical features are motor and sensory deficits that are highly suggestive of spinal cord (SC) damage. Objective:: To...
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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 unde...
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Pathogens, particularly human herpesviruses (HHVs), are implicated as triggers of disease onset/progression in multiple sclerosis (MS) and other neuroinflammatory disorders. However, the time between viral acquisition in childhood and disease onset in adulthood complicates the study of this association. Using nonhuman primates, we demonstrate that...
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Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. Although it has been extensively studied, the proximate trigger of the immune response remains uncertain. Experimental autoimmune encephalomyelitis in the common marmoset recapitulates many radiological and pathological features of focal multiple sclerosis le...
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Background and purpose: MAGL (monoacylglycerol lipase) is an enzyme that hydrolyzes the endocannabinoid 2-arachidonoylglycerol and regulates the production of arachidonic acid and prostaglandins-substances that mediate tissue inflammatory response. Here, we have studied the effects of the selective MAGL inhibitors JZL184 and MJN110 and their under...
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Understanding the spatiotemporal features of the hemodynamic response function (HRF) to brain stimulation is essential for the correct application of neuroimaging methods to study brain function. Here, we investigated the spatiotemporal evolution of the blood oxygen level-dependent (BOLD) and cerebral blood volume (CBV) HRF in conscious, awake marm...
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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. How...
Article
The primate auditory cortex is organized into a network of anatomically and functionally distinct processing fields. Because of its tonotopic properties, the auditory core has been the main target of neurophysiological studies ranging from sensory encoding to perceptual decision-making. By comparison, the auditory belt has been less extensively stu...
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Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) has become a major tool to map neural activity. However, the spatiotemporal characteristics of the BOLD functional hemodynamic response across the cortical layers remain poorly understood. While human fMRI studies suffer from low spatiotemporal resolution, the use...
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Magnetic resonance imaging (MRI) allows for the delineation between normal and abnormal tissue on a macroscopic scale, sampling an entire tissue volume three-dimensionally. While MRI is an extremely sensitive tool for detecting tissue abnormalities, association of signal changes with an underlying pathological process is usually not straightforward...
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Chronic monitoring of neuronal activity in the living brain with optical imaging techniques became feasible owing to the continued development of genetically encoded calcium indicators (GECIs). Here we report for the first time the successful generation of transgenic marmosets (Callithrix jacchus), an important nonhuman primate model in neurophysio...
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The common marmoset (Callithrix jacchus) is a small New World monkey that has gained significant recent interest in neuroscience research, due in great part for its compatibility with gene editing techniques, but also due to its tremendous versatility as an experimental animal model. Neuroimaging modalities, including anatomical (MRI) and functiona...
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The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Her...
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Purpose: The common marmoset (Callithrix jacchus) is a New World primate of increasing interest to neuroscience and in translational brain research. The present work describes the design and implementation of individualized 8-channel receive-only radiofrequency (RF) coil arrays that provide whole-brain coverage and allow anatomical and functional...
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Background: Marmosets are a powerful, emerging model for human behavior and neurological disorders. However, longitudinal imaging modalities that visualize both cellular structure and function within the cortex are not available in this animal model. Hence, we implemented an approach to quantify vascular topology, hemodynamics, and neural activity...
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Full-text available
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 dise...
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In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to achieve 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 connect...
Article
Magnetic resonance imaging (MRI) sensitivity approaches vessel specificity. We developed a single-vessel functional MRI (fMRI) method to image the contribution of vascular components to blood oxygenation level-dependent (BOLD) and cerebral blood volume (CBV) fMRI signal. We mapped individual vessels penetrating the rat somatosensory cortex with 100...
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Background: MRI 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 comparison...
Article
The common marmoset (Callithrix jacchus) is a New World monkey that has shown promise as a model for visual neuroscience. Recently we identified several face-selective patches along the occipitotemporal cortex whose configuration resembles those of macaque. Here we investigated neural responses inside and outside face patches during free viewing of...
Article
Oneofthegreatstrengthsofthemousemodelisthewidearrayofgenetictoolsthathavebeendeveloped.Strik-ingexamplesincludemethodsfordirectedmodificationofthegenome,andforregulatedexpressionorinacti-vation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators,andopsinsinspecificneuronaltypesinthemouse.However,th...
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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...
Article
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 sp...
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Full-text available
The cerebral cortex of humans and macaques has specialized regions for processing faces and other visual stimulus categories. It is unknown whether a similar functional organization exists in New World monkeys, such as the common marmoset (Callithrix jacchus), a species of growing interest as a primate model in neuroscience. To address this questio...
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Objective: Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in th...
Article
The correlation between temporal changes of regional cerebral blood flow (rCBF) and the severity of transient ischemic stroke in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) was investigated using T2-, diffusion- and perfusion-weighted magnetic resonance imaging at six different time points: before and during 1 hour of unilater...
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Purpose: To quantify the amplitude and temporal aspects of the blood oxygenation level-dependent (BOLD) response to an auditory stimulus during normocapnia and hypercapnia in healthy subjects in order to establish which BOLD parameters are best suited to infer the cerebrovascular reactivity (CVR) in the middle cerebral artery (MCA) territory. Mat...
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fMRI has established itself as the main research tool in neuroscience and brain cognitive research. The common marmoset (Callithrix jacchus) is a non-human primate model of increasing interest in biomedical research. However, commercial MRI coils for marmosets are not generally available. The present work describes the design and construction of a...
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Resting-state functional MRI is a powerful tool that is increasingly used as a noninvasive method for investigating whole-brain circuitry and holds great potential as a possible diagnostic for disease. Despite this potential, few resting-state studies have used animal models (of which nonhuman primates represent our best opportunity of understandin...
Article
Genetic variability in the strength and precision of fear memory is hypothesised to contribute to the etiology of anxiety disorders, including post-traumatic stress disorder. We generated fear-susceptible (F-S) or fear-resistant (F-R) phenotypes from an F8 advanced intercross line (AIL) of C57BL/6J and DBA/2J inbred mice by selective breeding. We i...