Background

Non-human primates (NHPs) are widely used as a species model in medical and life science research since they are the phylogenetically closest animal species to humans among those used for invasive experiments. In the field of systems neuroscience, research using NHPs have provided fundamental knowledge regarding neural mechanisms underlying the higher brain functions that are substantially evolved in humans, such as visual processing (Dubner and Zeki, 1971; Hubel and Wiesel, 1968; Perrett et al., 1982), decision making (Shadlen and Newsome, 2001; Padoa-Schioppa and Assad, 2006), working memory (Funahashi et al., 1989; Miller et al., 1996), attention (Treue and Maunsell, 1996; Luck et al., 1997), meta-cognition (Middlebrooks and Sommer, 2012; Miyamoto et al., 2017), and sociality (Gallese et al., 1996; Noritake et al., 2018). NHP research has also shown abnormal neural activity patterns in specific brain regions of animal models for neurological and psychiatric disorders, which are potentially physiological mechanisms underlying these disorders (Langston et al., 1984; Jentsch et al., 1997). These investigations provide insight into “where” and “how” the brain should be treated, and have therefore served as a basis for the development of therapeutic approaches for these disorders.

A remarkable achievement of neuroscience research using NHPs has been to advance our understanding of the relationship between neuronal activity and animal behavior. These studies employ specifically designed, well-controlled behavioral tasks, and record neuronal activity at high spatial and temporal resolutions while animals perform the tasks. These behavioral tasks need to finely control sensory inputs, accurately monitor behavioral responses, and precisely determine the time of task events. Neuronal activity recording has been implemented using several procedures. among which single-unit recording has been widely used due to its high spatial and temporal resolutions. By coupling these behavioral and recording procedures, NHP research has demonstrated that neuronal activities are tightly linked to specific sensory inputs, behavioral responses, and presumed internal processes at the single-unit level since the 1960s (Evarts, 1966; Wurtz, 1968).

Most NHP neuroscience research has been carried out in macaque monkeys, although other NHPs such as marmosets and squirrel monkeys have also been utilized. Our research group has conducted single-unit recording during which macaque monkeys performed behavioral tasks (Matsumoto and Takada, 2013; Kawai et al., 2015; Ogasawara et al., 2018). Figure 1 shows an overview of the experimental setup that allows collection of neuronal and behavioral data simultaneously across a unified timeline. Recently, we used this experimental setup to study the neural mechanisms underlying economic decision-making. We conducted single-unit recording of midbrain dopamine neurons and the orbitofrontal cortex while macaque monkeys performed an economic decision-making task (Figure 2A). In this task, six visual objects were associated with different amounts of a liquid reward, and two of them were randomly offered in sequence. When the first object was presented, the monkey needed to decide either to choose the first object by releasing the button or wait for the upcoming second object by continuing to press the button. The monkey obtained the reward associated with the chosen object at the end of the trial (Yun et al., 2020). This task design enabled us to continuously monitor neuronal activity while decisions were being made during the presentation of the first object, that is, as the monkey evaluated the first object, decided whether to choose it, and expressed the choice by releasing the button. We demonstrated that, while macaque monkeys were making an economic decision, midbrain dopamine neurons exhibited dynamically changing signals related to internal processing, such as value evaluation and identification of a chosen option (Yun et al., 2020). Here, we introduce the detailed experimental procedure used in this original study.

Figure 1. Schematic illustration of the entire behavioral and neuronal recording system.This illustration shows the configurations of apparatuses, how behavioral and neuronal data are collected by the TEMPO experimental control system, and how this system controls task events. The TEMPO experimental control system consists of three computers: Vsync, Server, and Client.

Figure 2. Economic decision-making task. A. Task design. This figure was reproduced with permission from our original paper (Yun et al., 2020. Figure 1A). B and C. The sequence of task events for trials in which a monkey decides to choose the first object or (B) the second object (C). ITI, intertrial interval; RT, choice reaction time.