Neuronal networks for control of eye movement

National Eye Institute

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Abstract

The thalamus is known to process information from various brain regions and relay it to other brain regions, serving an essential role in sensory perception and motor execution. The thalamus also receives inputs from basal ganglia nuclei (BG) involved in value-based decision making, suggesting a role in the value process. We found that neurons in a particular area of the rhesus macaque posterior thalamus encoded the historical value memory of visual objects. Many of these value-coding neurons were located in the suprageniculate nucleus (SGN). This thalamic area directly received anatomical input from the superior colliculus (SC), and the neurons showed visual responses with contralateral preferences. Notably, the value discrimination activity of these thalamic neurons increased during learning, with the learned values stably retained even more than 200 days after learning. Our data indicate that single neurons in the posterior thalamus not only processed simple visual information but also represented historical values. Furthermore, our data suggest an SC-posterior thalamus-BG-SC subcortical loop circuit that encodes the historical value, enabling a quick automatic gaze by bypassing the visual cortex. A primary function of the primate amygdala is to modulate behavior based on emotional cues. To study the underlying neural mechanism, we first inactivated the amygdala locally and temporarily by injecting a GABA agonist. Then, saccadic eye movements and gaze were suppressed only on the contralateral side. Next, we performed optogenetic activation after injecting a viral vector into the amygdala. Optical stimulation in the amygdala excited amygdala neurons, whereas optical stimulation of axon terminals in the substantia nigra pars reticulata inhibited nigra neurons. Optical stimulation in either structure facilitated saccades to the contralateral side. These data suggest that the amygdala controls saccades and gaze through the basal ganglia output to the superior colliculus. Importantly, this amygdala-derived circuit mediates emotional context information, whereas the internal basal ganglia circuit mediates object value information. This finding demonstrates a basic mechanism whereby basal ganglia output can be modulated by other areas conveying distinct information. In the primate basal ganglia, the caudate tail (CDt) encodes the historical values (good or bad) of visual objects (i.e., stable values), and electrical stimulation of CDt evokes saccadic eye movements. However, it is still unknown how output from CDt conveys stable value signals to govern behavior. Here, we apply a pathway-selective optogenetic manipulation to elucidate how such value information modulates saccades. We express channelrhodopsin-2 in CDt delivered by viral vector injections. Selective optical activation of CDt-derived terminals in the substantia nigra pars reticulata (SNr) inhibits SNr neurons. Notably, these SNr neurons show inhibitory responses to good objects. Furthermore, the optical stimulation causes prolonged excitation of visual-saccadic neurons in the superior colliculus (SC), and induces contralateral saccades. These SC neurons respond more strongly to good than to bad objects in the contralateral hemifield. The present results demonstrate that CDt facilitates saccades toward good objects by serial inhibitory pathways through SNr. The essential everyday task of making appropriate choices is a process controlled mainly by the basal ganglia. To this end, subjects need not only to find "good" objects in their environment but also to reject "bad" objects. To reveal this rejection mechanism, we created a sequential saccade choice task for monkeys and studied the role of the indirect pathway from the CDt (tail of the caudate nucleus) mediated by cvGPe (caudal-ventral globus pallidus externus). Neurons in cvGPe were typically inhibited by the appearance of bad objects; however, this inhibition was reduced on trials when the monkeys made undesired saccades to the bad objects. Moreover, disrupting the inhibitory influence of CDt on cvGPe by local injection of bicuculline (GABAA receptor antagonist) impaired the monkeys' ability to suppress saccades to bad objects. Thus, the indirect pathway mediates the rejection of bad choices, a crucial component of goal-directed behavior.