Neuronal networks for control of eye movement

National Eye Institute

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Abstract

In one project completed in the past year, we investigated the function of the external segment of the globus pallidus (GPe). This brain structure has been conventionally regarded as a key relay in the indirect pathway of the basal ganglia, primarily mediating movement suppression. However, recent studies in rodents suggest a more complex role, including active facilitation of actions. We recently investigated whether the primate GPe exhibits similar functional diversity by recording single-unit activity in two macaque monkeys performing a novel sequential choice task. This task separated the process of action initiation and suppression by requiring the monkeys to either accept a "good" object for reward or reject a "bad" object using one of multiple strategies. We identified three distinct neuronal clusters based on their firing patterns. Clusters 1 and 2 were linked to action facilitation: cluster 1 increased activity for saccades to both object types, while cluster 2 was selectively active for good-object saccades and suppressed during rejections-similar to cluster 3, which showed suppression during bad-object rejection. Local pharmacological blockade of glutamate receptors within the caudal dorsal GPe prolonged saccade latencies and reduced the frequency of rejection saccades, confirming a causal role for excitatory drive in saccade facilitation. These findings expand the traditional view of the GPe beyond a purely inhibitory station, indicating that in primates, it simultaneously mediates both motor facilitation and proactive suppression. Our results emphasize the importance of characterizing circuit-specific and cell-type-specific roles of the GPe within basal ganglia networks, with implications for normal motor function and movement disorder pathophysiology under complex reward-based decision processes in non-human primates. In another set of studies that we completed in this period, we examined why voluntary eye movements directed to high-valued objects in the environment are executed with greater vigor than eye movements to low-valued objects. Our study focused on the Superior Colliculus (SC), a subcortical structure that controls eye movements and that contains multiple subtypes of neurons that have distinct functional roles in generating saccades. How does value-related information processed in other parts of the brain affect the responses of these different subtypes of SC neurons to facilitate faster saccades? To test this, we recorded four subtypes of neurons simultaneously while the monkey made saccades to objects they had been extensively trained to associate with large or small rewards (i.e., good or bad). In three subtypes of neurons (visual, visuomotor, and motor), the good objects elicited more spikes than bad objects. More importantly, using a bootstrapping procedure, we identified three separable phases of activity: 1) early visual response (EVIS), 2) late visual response (LVIS), and 3) pre-saccadic (PreSAC) motor response in these neuronal subtypes. In each subtype of neurons, the value of objects (good vs. bad) was positively correlated with the activity in the LVIS and PreSAC phases but not the EVIS phase. These data suggest that the value information from other brain regions modulates the visual (LVIS) and the motor (PreSAC) responses of visual, visuomotor, and motor neurons. This enhanced activation facilitates the faster initiation and execution of the saccade based on the value of each object. In addition, we found a novel class of tonically active neurons that decrease their activity in response to object onset and remain inhibited till the end of the saccade. We suggest that these tonic neurons facilitate the saccade to objects by disinhibiting the interactions between the other three types of SC neurons.