Okihide Hikosaka

2018 Neuroscience Prize

Laureate Profile

Okihide Hikosaka, MD, PhD, of the National Institutes of Health’s National Eye Institute (NEI), has made groundbreaking discoveries regarding the role played by the basal ganglia — clusters of neurons located deep in the forebrain — in behavior. While working during the early 1980s as a postdoctoral researcher with neuroscientist Robert Wurtz, Hikosaka discovered that neurons found in the substantia nigra pars reticulata, which is part of the basal ganglia, have key connections to the superior colliculus, a brain structure that transforms sensory input into movement output, including saccadic, or voluntary, eye movements. After returning to Japan, Hikosaka continued to study the basal ganglia, making a string of remarkable findings. He showed, for example, that eye movements made by monkeys in anticipation of an expected reward were the result of tonic neural inhibition and a quick release of the inhibition in an area of the basal ganglia known as the caudate nucleus, and that a distinct type of dopamine neurons was involved in this process. Hikosaka then found that the basal ganglia play a central role in complex hand movements. Importantly, the anterior and posterior parts of the basal ganglia work separately for the initial learning and the later skillful performance. After his return to NEI, Hikosaka extended his research on the basal ganglia and related brain areas. He demonstrated that dopamine neurons function differently in different areas of the basal ganglia — findings that upended the then-existing view of the role of dopamine neurons in emotion and motivation. Hikosaka also demonstrated that neurons in the lateral habenula, which receives input from the basal ganglia, become activated when animals are either not rewarded or are “punished” with an air puff to the face. In recent years Hikosaka found that old reward histories create long-term value memories of many objects and that animals are automatically attracted by the historically good objects. This behavior is controlled selectively by the very posterior part of the basal ganglia (tail of the caudate nucleus – substantia nigra pars reticulata – superior colliculus). By greatly expanding our understanding of the brain’s reward and memory system, Hikosaka’s work has opened up exciting new avenues of research — not just for the study of motivation, but also for unraveling the neurobiological underpinnings of many neuropsychiatric disorders, including depression, schizophrenia and drug addiction.