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

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.

Common coding of expected value and value uncertainty memories in the prefrontal cortex and basal ganglia output

“…Given the anatomical and functional projection from vlPFC and cdlSNr to superior colliculus ( Fig. 8F ), it is very likely that the observed neuronal enhancements underlie the behavioral bias observed in free viewing ( 7 , 11 , 30 , 31 ). Reward uncertainty is shown to be encoded in an additive fashion to expected reward or independent from it in various regions including anterodorsal septum, basal forebrain, anterior cingulate cortex, and caudate head ( 16 , 32 – 34 ) in tasks with active reward anticipation.…”

Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making

“…Recent advances in specific neuronal manipulation tools have drastically enhanced our understandings of the functional roles of individual neural pathways in small animals such as rodents (24,53). Nonetheless, the application of pathway-selective manipulations to non-human primates is still largely limited by using either optogenetic terminal activation (19)(20)(21) or double-vector methods (15)(16)(17)(18), neither of which is capable of testing dissociable function of multiple neural pathways in individual subjects. Using a chemogenetic approach, the current study succeeded in the double-dissociation of the roles of two distinct pathways in individual monkeys.…”

“…Optogenetics is another approach to manipulating the neuronal activity of a specific pathway by optical stimulation of axon-terminal sites. Although a few studies have succeeded in pathway-specific optogenetic activation in nonhuman primates (19)(20)(21), optogenetic silencing of synaptic transmission remains challenging (22,23). Moreover, these approaches require precise identification of the locations of anatomically-connected multiple regions, i.e., viral injection or allocation of optic fiber, which is technically demanding when using non-human primates because of limited resources.…”

Environment-based object values learned by local network in the striatum tail

“…According to our previous research, the basal ganglia play a crucial role in choosing good objects and rejecting bad objects ( 1 , 2 ). This is done consistently by the population of output neurons (MSNs) in the STRt (caudate and putamen) ( 9 , 11 ) whose outputs are mediated by the superior colliculus (SC) and are used for gaze bias toward good objects ( 25 ). How then can this circuit switch the output based on the environment?…”