Fluorescent dope

Kyoto, Japan -- We're all familiar with Pavlovian conditioning, in which a reward-anticipatory behavior follows a reward-predicting stimulus. Perhaps you experience it yourself when passing a café or restaurant and catching a whiff of something delectable.

Behind this mechanism is dopamine released within the striatum, the largest structure of the subcortical basal ganglia, which links motor movements and motivation. Yet it has remained unclear exactly what kind of dopamine signal is transmitted to the striatum to cause this behavior in primates.

In order to understand this dopamine signal, a team of researchers from Kyoto University and Cambridge University developed a new method of monitoring dopamine, utilizing a fluorescent dopamine sensor.

"We found that the fluorescence monitoring technique is widely suitable for identifying the physiological functions of dopamine and other substances in the brain," says corresponding author Hidetoshi Amita.

The team observed rhesus macaques living in KyotoU's Center for the Evolutionary Origins of Human Behavior, in Aichi prefecture. First they engaged the monkeys in a Pavlovian probabilistic reward task, involving fractal objects presented on a screen paired with reward delivery. After training the monkeys for two months, they applied a dopamine monitoring technique with a fluorescent sensor, after which they analyzed the monkeys' licking and gazing behaviors while performing the same reward task. The team's fluorescent methods proved effective.

"Our study demonstrates that this technique is useful in capturing the dopamine transients in brain structures of the task-performing monkeys," continues Amita.

Upon analyzing the fluorescent dopamine signals, the researchers found that the signals varied depending on the location in the striatum. In particular, they observed distinct patterns of dopamine signaling to the anterior putamen and the caudate head, two structures which together form the dorsal striatum. The signals in the anterior putamen exhibited a positive response to the unpredicted reward, while those in the caudate head showed a weak response.

This is significant because the dorsal striatum plays an important role in mediating cognition and motor function, and its two components play different roles in behavior and skill acquisition. This makes them crucial in studying neurodegenerative diseases.

"This may be the cause of the various functional impairments observed in progressive neurodegenerative diseases, such as Parkinson's disease and Lewy body dementia," says Amita.

Understanding the pathophysiology of such diseases will require further studies on primates to explore dopamine functions in specific striatal regions. This new method of fluorescent dopamine signaling could play a significant role in aiding better understanding of these conditions.

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The paper "Fluorescence detection of dopamine signaling to the primate striatum in relation to stimulus-reward associations" appeared on 14 March 2025 in Proceedings of the National Academy of Sciences of the United States of America, with doi: 10.1073/pnas.2426861122

About Kyoto University

Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at undergraduate and graduate levels complements several research centers, facilities, and offices around Japan and the world. For more information, please see: http://www.kyoto-u.ac.jp/en