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Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Everling, Stefan

Abstract

Common marmosets (Callithrix jacchus) are small-bodied New World primates that are increasingly popular as model animals for neuroscience research. Their lissencephalic cortex provides substantial advantages for the application of high-density electrophysiological techniques to enhance our understanding of local cortical circuits and their cognitive and motor functions. The oculomotor circuitry underlying saccadic eye movements has been a popular system to study cognitive control. Most of what we know about this system, comes from electrophysiological studies on macaques, but most of their cortical oculomotor areas are buried within sulci and harder to access for high-density recordings. In contrast, marmosets provide greater advantages for studies of the oculomotor system, since critical areas of this network such as the frontal eye fields (FEF) and lateral intraparietal area (LIP) are easily accessible at the cortical surface. In contrast to the well-established macaques, little is known about functional connectivity patterns of common marmosets. In this thesis, we used resting-state ultra-high-field fMRI on anesthetized marmosets and macaques along with awake human subjects, to examine and compare the functional organization of the brain, with emphasis on the saccade system. Independent component analysis revealed homologous resting-state networks in marmoset to those in macaques and humans, including a distributed frontoparietal network. Seed-region analyses of the marmoset superior colliculus (SC) revealed the strongest frontal functional connectivity with area 8aD bordering area 6DR. This frontal region exhibited a similar functional connectivity pattern to the FEF in macaques and humans. The results supported an evolutionarily preserved frontoparietal system and provided a starting point for invasive neurophysiological studies in the marmoset saccade system. We started by investigating the function of the marmoset posterior parietal cortex with electrical microstimulation. We implanted 32-channel Utah arrays at the location of area LIP as identified from our resting-state fMRI study and applied microstimulation while animals watched videos. Similar to macaque studies, stimulation evoked fixed-vector and goal-directed saccades, staircase saccades, and eyeblinks in marmosets. These findings demonstrated that the marmoset area LIP plays a role in the regulation of eye movements and is potentially homologous to that of the macaque. Next, we recorded the neuronal activity in marmoset areas LIP and 8aD using linear electrode arrays while animals performed a pro/antisaccade task. The antisaccade task is a popular paradigm to probe executive control. In this task, participants suppress a prepotent stimulus-driven response in favor of a less potent response away from the stimulus. Our behavioral findings indicated that area 8aD neurons were significantly more active for correct than errorenous antisaccades in contralateral directions, with respect to the recording site. We found neurons with significant stimulus-related activity in area LIP and significant saccade-related neurons in both areas 8aD and LIP. These findings provided further evidence on the role of marmoset frontal and parietal oculomotor areas in oculomotor control, supporting marmosets as alternative primate models of the oculomotor system.

Summary for Lay Audience

The oculomotor system is a brain circuitry that underlies saccades, which are rapid eye movements that we naturally do to visually observe our environment. Most of what we know about this system, comes from electrophysiological studies on macaque monkeys. However, when it comes to more advanced electrophysiological techniques, macaque’s brain with its extensive cortical folding makes it hard to access cortical oculomotor areas that are buried deep within the folds. On the other hand, common marmoset monkeys are small-bodied primates with a smooth cortex that allows easier access to oculomotor areas right at the surface of the brain, providing substantial advantages for higher density recording techniques. To consider marmosets as alternative primate models of the oculomotor system, it is necessary to investigate the functional organization of this system in these species and identify homologous oculomotor areas that serve a similar function to that of the macaque. My PhD project aimed to investigate that through a range of experimental techniques. We used the resting-state fMRI technique to explore the functional organization of marmoset brain and identified a frontoparietal network that potentially represented the oculomotor system. We identified brain areas such as area 8aD and the lateral intraparietal area (LIP) within this network that had a similar pattern of functional connectivity to the corresponding oculomotor areas in the macaque. Our findings supported a preserved frontoparietal network in these species and allowed for more invasive investigation of the identified oculomotor areas with electrophysiology. We chose to investigate area LIP as identified from our fMRI findings, using electrical microstimulation techniques. The goal was to examine whether the stimulation of area LIP in marmoset will evoke saccadic eye movements. Similar to macaque studies, we found that microstimulating area LIP in marmosets elicited both fixed-vector and goal-directed saccades. Our findings demonstrated that area LIP in marmosets has a similar role in regulating eye movements to that of the macaque and is potentially homologous to it. Next, we recorded neuronal activity in areas LIP and 8aD of marmosets while the animal was performing a saccadic eye movement task called the pro/antisaccade task. We found neurons within each area that demonstrated significant saccade related activity in specific epochs of the task. These findings provided further evidence on the role of marmoset oculomotor areas in saccadic eye movements and supported common marmosets as alternative primate models of the oculomotor system.

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