Optogenetic manipulation of a value-coding pathway from the primate caudate tail facilitates saccadic gaze shift

Hidetoshi Amita,Hyoung F Kim,Okihide Hikosaka,Masahiko Takada,Ken-Ichi Inoue

doi:10.1038/s41467-020-15802-y

Abstract

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.

Highlights

IntroductionIn 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
In the primate basal ganglia, the caudate tail (CDt) encodes the historical values of visual objects, and electrical stimulation of CDt evokes saccadic eye movements
We found that the selective activation of the direct CDt-cdlSNr pathway conveying stable value signals facilitated contralateral saccades through the disinhibition of superior colliculus (SC), whereas the activation of the indirect CDt-cvGPe pathway showed no significant effect on saccades

Summary

Introduction

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. A network model involving especially the rostral aspect of the basal ganglia explains the mechanism of saccadic eye movements:[3] First, excitation of the caudate nucleus (CD) causes inhibition of the substantia nigra pars reticulata (SNr)[4,5,6], which causes excitation of the superior colliculus (SC) via disinhibition[7,8] This excitation of SC evokes the contralateral saccade[9,10,11,12,13,14,15]. The circuitry of the caudal aspect of the basal ganglia parallels that of the rostral aspect: the tail of the caudate nucleus (CDt) projects to the caudal–dorsal–lateral SNr (cdlSNr or the substantia nigra pars lateralis)[24], which in turn sends projection fibers to SC16,25 Taken together, these studies suggest that the direct pathway from CDt (i.e., the CDt-cdlSNr pathway) controls saccadic eye movements based on reward history through the disinhibition of SC. We conclude that the multisynaptic CDt-cdlSNr-SC pathway encoding the stable value plays a crucial role in generation of saccades toward good objects within the contralateral hemifield

Methods

Results

Conclusion