The common marmoset (Callithrix jacchus) is a New World primate that is becoming increasingly popular as a preclinical model. To assess functional connectivity (FC) across the marmoset brain, resting-state functional MRI (RS-fMRI) is often performed under isoflurane anesthesia to avoid the effects of motion, physiological stress, and training requirements. In marmosets, however, it remains unclear how isoflurane anesthesia affects patterns of FC. Here, we investigated the effects of isoflurane on FC when delivered with either medical air or 100% pure oxygen, two canonical methods of inhalant isoflurane anesthesia delivery. The results demonstrated that when delivered with either medical air or 100% oxygen, isoflurane globally decreased FC across resting-state networks that were identified in awake marmosets. Generally, although isoflurane globally decreased FC in resting-state networks, the spatial structure of the networks was preserved. Outside of the context of RS networks, we indexed pair-wise functional connectivity between regions across the brain and found that isoflurane substantially altered interhemispheric and thalamic FC. Taken together, these findings indicate that RS-fMRI under isoflurane anesthesia is useful to evaluate the global structure of functional networks, but may obfuscate important nodes of some network components when compared to data acquired in fully awake marmosets.
The frontal eye field (FEF) is a critical region for the deployment of overt and covert spatial attention. Although 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 three adult marmosets (two males, one female). We implanted marmosets with 96-channel Utah arrays and applied microstimulation trains while they freely viewed video clips. We evoked shortlatency fixed vector saccades at low currents (Ͻ50 A) in areas 45, 8aV, 8C, and 6DR. We observed a topography of saccade direction and amplitude consistent with findings in macaques and humans: 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 that the marmoset is a useful primate model for investigating FEF microcircuitry and its contributions to oculomotor and cognitive functions.
Understanding the similarity of cortico-subcortical networks topologies between humans and nonhuman primate species is critical to study the origin of network alternations underlying human neurological and neuropsychiatric diseases. The New World common marmoset (Callithrix jacchus) has become popular as a non-human primate model for human brain function. Most marmoset connectomic research, however, has exclusively focused on cortical areas, with connectivity to subcortical networks less extensively explored. In this study, we aimed to first isolate patterns of subcortical connectivity with cortical resting-state networks (RSNs) in awake marmosets using resting-state functional magnetic resonance imaging (RS-fMRI), then to compare these networks to those in humans using connectivity fingerprinting.While we could match several marmoset and human RSNs based on their functional fingerprints, we also found a few striking differences, for example strong functional connectivity of the default mode network with the superior colliculus in marmosets that was much weaker in humans. Together, these findings demonstrate that many of the core cortico-subcortical networks in humans are also present in marmosets, but that small, potentially functionally relevant differences exist..
The 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.
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.
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