scholarly journals Functional localization of the frontal eye fields in the common marmoset using microstimulation

2019 ◽  
Author(s):  
Janahan Selvanayagam ◽  
Kevin D. Johnston ◽  
David J. Schaeffer ◽  
Lauren K. Hayrynen ◽  
Stefan Everling
Keyword(s):  
Spatial Attention ◽  
Common Marmoset ◽  
Frontal Eye Field ◽  
Cortical Region ◽  
Compelling Evidence ◽  
Primate Model ◽  
Promising Alternative ◽  
Cortical Areas ◽  
Eye Field ◽  
The Common

AbstractThe frontal eye field (FEF) is a critical region for the deployment of overt and covert spatial attention. While investigations in the macaque continue to provide insight into the neural underpinnings of the FEF, due to its location within a sulcus the macaque FEF is virtually inaccessible to electrophysiological techniques such as high-density and laminar recordings. With a largely lissencephalic cortex, the common marmoset (Callithrix jacchus) is a promising alternative primate model for studying FEF microcircuitry. Putative homologies have been established with the macaque FEF on the basis of cytoarchitecture and connectivity, however physiological investigation in awake, behaving marmosets is necessary to physiologically locate this area. Here we addressed this gap using intracortical microstimulation in a broad range of frontal cortical areas in marmosets. We implanted marmosets with 96-channel Utah arrays and applied microstimulation trains while they freely viewed video clips. We evoked short-latency fixed vector saccades at low currents (<50 μA) in areas 45, 8aV, 8C and 6DR. We observed a topography of saccade direction and amplitude consistent with findings in macaques and humans; we observed small saccades in ventrolateral FEF and large saccades combined with contralateral neck and shoulder movements encoded in dorsomedial FEF. Our data provide compelling evidence supporting homology between marmoset and macaque FEF and suggest the marmoset is a useful primate model for investigating FEF microcircuitry and its contributions to oculomotor and cognitive functions.Significance StatementThe frontal eye field (FEF) is a critical cortical region for overt and covert spatial attention. The microcircuitry of this area remains poorly understood, as in the macaque, the most commonly used model, it is embedded within a sulcus and is inaccessible to modern electrophysiological and optical imaging techniques. The common marmoset is a promising alternative primate model due to its lissencephalic cortex and potential for genetic manipulation. However, evidence for homologous cortical areas in this model remains limited and unclear. Here we applied microstimulation in frontal cortical areas in marmosets to physiologically identify the FEF. Our results provide compelling evidence for a frontal eye field in the marmoset, and suggest that the marmoset is a useful model for FEF microcircuitry.

scholarly journals Electrical microstimulation evokes saccades in posterior parietal cortex of common marmosets

2019 ◽  
Vol 122 (4) ◽  
pp. 1765-1776 ◽  
Author(s):  
Maryam Ghahremani ◽  
Kevin D. Johnston ◽  
Liya Ma ◽  
Lauren K. Hayrynen ◽  
Stefan Everling
Keyword(s):  
Eye Movements ◽  
Parietal Cortex ◽  
Posterior Parietal Cortex ◽  
Common Marmoset ◽  
Primate Species ◽  
Oculomotor Control ◽  
Electrical Microstimulation ◽  
Cortical Areas ◽  
Posterior Parietal ◽  
The Common

The common marmoset ( Callithrix jacchus) is a small-bodied New World primate increasing in prominence as a model animal for neuroscience research. The lissencephalic cortex of this primate species provides substantial advantages for the application of electrophysiological techniques such as high-density and laminar recordings, which have the capacity to advance our understanding of local and laminar cortical circuits and their roles in cognitive and motor functions. This is particularly the case with respect to the oculomotor system, as critical cortical areas of this network such as the frontal eye fields (FEF) and lateral intraparietal area (LIP) lie deep within sulci in macaques. Studies of cytoarchitecture and connectivity have established putative homologies between cortical oculomotor fields in marmoset and macaque, but physiological investigations of these areas, particularly in awake marmosets, have yet to be carried out. Here we addressed this gap by probing the function of posterior parietal cortex of the common marmoset with electrical microstimulation. We implanted two animals with 32-channel Utah arrays at the location of the putative area LIP and applied microstimulation while they viewed a video display and made untrained eye movements. Similar to previous studies in macaques, stimulation evoked fixed-vector and goal-directed saccades, staircase saccades, and eyeblinks. These data demonstrate that area LIP of the marmoset plays a role in the regulation of eye movements, provide additional evidence that this area is homologous with that of the macaque, and further establish the marmoset as a valuable model for neurophysiological investigations of oculomotor and cognitive control. NEW & NOTEWORTHY The macaque monkey has been the preeminent model for investigations of oculomotor control, but studies of cortical areas are limited, as many of these areas are buried within sulci in this species. Here we applied electrical microstimulation to the putative area LIP of the lissencephalic cortex of awake marmosets. Similar to the macaque, microstimulation evoked contralateral saccades from this area, supporting the marmoset as a valuable model for studies of oculomotor control.

The Common Marmoset (Callithrix jacchus) as a Model in Toxicology

2003 ◽  
Vol 31 (1_suppl) ◽  
pp. 123-127 ◽  
Author(s):  
U. Zühlke ◽  
G. Weinbauer
Keyword(s):  
Animal Model ◽  
Current Knowledge ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Human Reproduction ◽  
Background Information ◽  
Reproductive Toxicology ◽  
Primate Model ◽  
Wide Range ◽  
The Common

The common marmoset, Callithrix jacchus, is the smallest nonhuman primate commonly used in biomedical research. Marmoset characteristics and propensities have enabled them to be used in a wide range of research as a model of human disease, physiology, drug metabolism, general toxicology, and reproductive biology. This paper provides a general overview of the marmoset with special emphasis on the benefits and disadvantages of this species as a model for inclusion in preclinical drug development programmes. In view of its small size in comparison with other nonrodent species marmosets have become of value for toxicology studies with biotechnology products where compound supply is limited. In general toxicology studies, marmosets have been successfully used to meet regulatory endpoints also for specific investigatory purposes. The widespread use of this species has allowed extensive background information to become available and a summary of the most frequently measured parameters are presented. Marmosets apparently represent an interesting animal model for comparative research on primate reproductive physiology. However, several basic aspects of reproductive processes exhibit cardinal discrepancies to those described for macaques and human. Thus, from the viewpoint of reproductive toxicology, the relevance of the marmoset primate model for human reproduction remains unclear to date and further research is obviously needed. Given our current knowledge of marmoset reproductive features, the use of this animal model cannot be recommended for reproductive toxicology assessment.

scholarly journals Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)

2013 ◽  
Vol 81 (8) ◽  
pp. 2909-2919 ◽  
Author(s):  
Laura E. Via ◽  
Danielle M. Weiner ◽  
Daniel Schimel ◽  
Philana Ling Lin ◽  
Emmanuel Dayao ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Human Disease ◽  
Small Animal ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Primate Model ◽  
Content Type ◽  
Positron Emission ◽  
The Common ◽  
Fdg Pet Ct

ABSTRACTExisting small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains ofMycobacterium tuberculosisof various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, andM. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with variousM. tuberculosisstrain clades.

scholarly journals Characterization of lethal inhalational infection with Francisella tularensis in the common marmoset (Callithrix jacchus)

2010 ◽  
Vol 59 (9) ◽  
pp. 1107-1113 ◽  
Author(s):  
Michelle Nelson ◽  
Mark S. Lever ◽  
Rachel E. Dean ◽  
Victoria L. Savage ◽  
F. Javier Salguero ◽  
...  
Keyword(s):  
Francisella Tularensis ◽  
Immunological Response ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Post Challenge ◽  
Primate Model ◽  
Immunological Parameters ◽  
Suitable Animal Model ◽  
The Common ◽  
Schu S4

The intracellular Gram-negative pathogen Francisella tularensis is the causative agent of tularaemia and is prevalent in many countries in the northern hemisphere. To determine whether the common marmoset (Callithrix jacchus) would be a suitable non-human primate model of inhalational tularaemia, a pathophysiology study was undertaken. Ten animals were challenged with ∼102 c.f.u. F. tularensis strain SCHU S4 (F. tularensis subsp. tularensis). To look for trends in the infection, pairs of animals were sacrificed at 24 h intervals between 0 and 96 h post-challenge and blood and organs were assessed for bacteriology, pathology and haematological and immunological parameters. The first indication of infection was a raised core temperature at 3 days post-challenge. This coincided with a number of other factors: a rapid increase in the number of bacteria isolated from all organs, more pronounced gross pathology and histopathology, and an increase in the immunological response. As the disease progressed, higher bacterial and cytokine levels were detected. More extensive pathology was observed, with multifocal lesions seen in the lungs, liver and spleen. Disease progression in the common marmoset appears to be consistent with human clinical and pathological features of tularaemia, indicating that this may be a suitable animal model for the investigation of novel medical interventions such as vaccines or therapeutics.

scholarly journals Exploring the Innate Immunological Response of an Alternative Nonhuman Primate Model of Infectious Disease; the Common Marmoset

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
M. Nelson ◽  
M. Loveday
Keyword(s):  
Infectious Disease ◽  
Immune Response ◽  
Nonhuman Primate ◽  
Immune Cell ◽  
Common Marmoset ◽  
Cell Types ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
The Common ◽  
Activation Status

The common marmoset (Callithrix jacchus) is increasingly being utilised as a nonhuman primate model for human disease, ranging from autoimmune to infectious disease. In order to fully exploit these models, meaningful comparison to the human host response is necessary. Commercially available reagents, primarily targeted to human cells, were utilised to assess the phenotype and activation status of key immune cell types and cytokines in naive and infected animals. Single cell suspensions of blood, spleen, and lung were examined. Generally, the phenotype of cells was comparable between humans and marmosets, with approximately 63% of all lymphocytes in the blood of marmosets being T cells, 25% B-cells, and 12% NK cells. The percentage of neutrophils in marmoset blood were more similar to human values than mouse values. Comparison of the activation status of cells following experimental systemic or inhalational infection exhibited different trends in different tissues, most obvious in cell types active in the innate immune response. This work significantly enhances the ability to understand the immune response in these animals and fortifies their use as models of infectious disease.

scholarly journals A New Primate Model of Focal Stroke: Endothelin-1—Induced Middle Cerebral Artery Occlusion and Reperfusion in the Common Marmoset

2004 ◽  
Vol 24 (1) ◽  
pp. 24-41 ◽  
Author(s):  
David Virley ◽  
Sarah J. Hadingham ◽  
Jenny C. Roberts ◽  
Belinda Farnfield ◽  
Heather Elliott ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Common Marmoset ◽  
Artery Occlusion ◽  
Primate Model ◽  
Endothelin 1 ◽  
The Common ◽  
Cerebral Artery Occlusion

The purpose of the present set of studies was to develop a new primate model of focal ischemia with reperfusion for long-term functional assessment in the common marmoset. Initially, the cerebral vascular anatomy of the marmoset was interrogated by Araldite-cast and ink-perfusion methods to determine the feasibility of an intravascular surgical approach. The methods showed that the internal carotid artery was highly tortuous in its passage, precluding the development of an extracranial method of inducing temporary middle cerebral artery occlusion in the marmoset. A pilot dose-response study investigated an intracranial approach of topically applying endothelin-1 (ET-1) to the M2 portion of the middle cerebral artery in a small sample of marmosets for up to 6 hours (n = 2 or 3 per group). Dose-dependent reductions in middle cerebral artery vessel caliber followed by gradual reperfusion were inversely related to increases in corrected lesion volume after ET-1 treatment, relative to vehicle control application. Finally, the functional consequences of ET-1–induced lesions to the M2 vascular territory were assessed up to 24 hours after surgery using the optimal dose established in the pilot study (2.5 nmol/25 μL). ET-1–treated marmosets (n = 4) showed marked contralateral motor deficits in grip strength and retrieval of food rewards and contralateral sensory/motor neglect towards tactile stimulation, relative to their ipsilateral side and vehicle-treated marmosets (n = 4). Strong correlations were shown between contralateral impairments and histopathologic parameters, which revealed unilateral putamen and cortical damage to the middle cerebral artery territory. No deficits were shown on general mobility, and self-care was promptly resumed in ET-1 marmosets after surgery. These results show that this novel model of ischemia with reperfusion in the marmoset has the potential to assess long-term function and to gauge the efficacy of novel therapeutic strategies targeted for clinical stroke.

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