Eye movements in monkeys with local dopamine depletion in the caudate nucleus. I. Deficits in spontaneous saccades

Abstract

The basal ganglia contribute to the suppression and initiation of saccadic eye movements through the inhibitory connection from the substantia nigra pars reticulata (SNr) to the superior colliculus. This mechanism consists of serial and parallel connections, which are mostly inhibitory and GABAergic. Dopamine is known to exert powerful modulatory effects on the basal ganglia function, but its nature and mechanism are still unclear, especially in relation to voluntary behavior. The purpose of this series of investigation was to study the role of dopamine in the control of saccadic eye movements. We examined, in the monkey, whether and how the deficiency of the nigrostriatal dopaminergic innervation affects saccadic eye movements. The present article is focused on spontaneous saccades that the monkey made with no incentive to obtain reward; the next paper will describe task-specific saccades. Using an osmotic minipump we infused 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) unilaterally into the head-body junction of the caudate nucleus of monkeys where presaccadic neurons were clustered. Tyrosine hydroxylase activity, visualized using an immunohistochemical method, decreased locally around the injection site with some effects extending into the ipsilateral putamen and locally in the ipsilateral substantia nigra. Changes of eye movements started to appear 3–5 d after starting the infusion. Spontaneous saccades became less frequent. The area scanned by the saccades became narrower and shifted to the hemifield ipsilateral to the infusion site. The saccade amplitudes and peak velocities decreased; durations were prolonged. These effects were more prominent for saccades directed toward the side contralateral to the infusion site. These monkeys showed no obvious skeletomotor symptoms. These results suggest that the local deprivation of the dopaminergic innervation in the caudate nucleus facilitates neuronal activity of the SNr leading to suppression of saccadic eye movements.

Enhanced sensory sampling precedes self-initiated locomotion in an electric fish

“…Cortical recordings reveal that neural activity precedes the time when a conscious decision to act is reported (Kornhuber and Deecke, 1965;Libet et al, 1983;Soon et al, 2008), raising questions as to how neural activity relates to conscious decision making and the initiation of voluntary actions. Whereas prior work has shown neural activity preceding voluntary actions in primates capable of advanced cognition (Romo and Schultz, 1987;Kato et al, 1995;Kaufman et al, 2010), here we demonstrate the same pattern in an aquatic vertebrate whose last common ancestor to primates lived more than 450 million years ago. We propose that volition may therefore be a primitive capability of vertebrate brains that precedes the advanced cognitive capacities of primates.…”

“…Sustained preparatory neural activities preceding voluntary movements have been reported in humans (Kornhuber and Deecke, 1965;Libet et al, 1983;Soon et al, 2008) and monkeys (Romo and Schultz, 1987;Kato et al, 1995;Kaufman et al, 2010). Here, however, we further demonstrate that the increased neural activity preceding self-initiated movement is also associated with a heightened sensory sampling (EODR) that precedes movement onset.…”

“…Prolonged preparatory neural activities characteristic to human voluntary actions are also found in diverse species including monkeys (Romo and Schultz, 1987;Kato et al, 1995;Kaufman et al, 2010) and rodents (Friedman et al, 2006); this suggests that the ability to self-initiate movement is a quantifiable biological trait shared across many vertebrate species including teleost fish. The experience of agency is essential for human volitional actions (Haggard, 2008), and the pre-supplementary motor area is shown to be activated when human subjects pay attention to their intention to act (Lau et al, 2004).…”

Subcortical Input to the Smooth and Saccadic Eye Movement Subregions of the Frontal Eye Field inCebusMonkey

“…One obvious difference is that the FEFsem receives a considerably richer input from the globus pallidus targets in the thalamus than does the FEFsac. In the past, most studies of basal ganglia and eye movements have focused on saccadic eye movements (Hikosaka and Wurtz, 1983a,b,c,d;Hikosaka, 1989;Hikosaka and Wurtz, 1989;Kato et al, 1995;Kori et al, 1995). To our knowledge, no recording studies in behaving subhuman primates have looked directly at the role of the basal ganglia in visual pursuit.…”

Neuronal Substrate of the Saccadic Inhibition Deficit in Schizophrenia Investigated With 3-Dimensional Event-Related Functional Magnetic Resonance Imaging

“…53,55 With these 2 connections, the striatum can facilitate or suppress overt oculomotor behavior and does so by transiently modulating the tonic inhibitory control that is exerted by the SNr on the SC. 29,56 The suppressed neuronal activity in the SC during saccadic inhibition probably reflects an effort to avoid fast reflexive saccades triggered by the SC through afferents of the nuclei of the optic tract or parietal regions. 2 Accordingly, the inhibition of saccades requires adequate input from a network that feeds into the SNr, which is most likely initiated in the frontal cortex.…”