Tadashi Isa graduated from the Faculty of Medicine, the University of Tokyo in 1985 and obtained PhD from the University of Tokyo on the brainstem control of eye and head movements in cats in 1989. He worked as a visiting scientist in the University of Göteborg in Sweden, under Professor Anders Lundberg from 1988 to 1990, on the descending control of hand and arm movements in cats. Then, he returned to Japan and became an assistant professor in the Institute for Brain Research in the University of Tokyo and continued his studies on the eye and head movement control. Then, he switched his target to molecular level of studies and worked on the molecular physiology of AMPA type glutamate receptors as a lecturer and associate professor in Gunma University in 1993-1995. He was then appointed to be a professor of the National Institute for Physiological Sciences in 1996. There he switched back to the system neuroscience studies, particularly on the neural mechanism of recovery of hand movements following the spinal cord injury and mechanism of eye movements and cognitive functions following the lesion of the primary visual cortex, that is, the animal model of blindsight. More recently, he is studying the neural mechanism of decision making in macaque monkeys using the state-of-art circuit mamipulation techniques including those developed by his own laboratory.     

Title：Roles of mesolimbic and mesofrontal dopaminergic pathway for motor recovery and decision making

Abstract：

Dopaminergic neurons in the ventral tegmental area (VTA) project to the striatum including the nucleus accumbens (NAc) and many cortical areas and are considered to regulate motivation and a variety of cognitive functions. Here, I talk about our recent studies on the functions of these mesolimbic and mesocortical dopaminergic pathways. First, our group found that NAc plays a critical role on the motor recovery after the spinal cord injuries (SCI)(Sawada et al. Science, 2015). NAc is considered not to be involved directly in the control of movements, but after the it starts to activate the motor cortices and gets involved in the direct control of hand movements through activation of the motor cortex. These results may open up a new strategy for enhancing the effects of neurorehabilitation.

Second, we found that selective blockade of the pathway from VTA to NAc impaired effort-based decision for the monkeys to get larger amount of reward by waiting long for its delivery, rather than the reward based reinforcement learning (Vancraeyenest et al. Neuron, 2020). Furthermore, more recently, we found that the mesocortical pathway from VTA to the lateral-ventral portion of the area6 (area 6V) is involved in the control of decision making involving risk-based decision making which might require higher level of computation. Selective optogenetic activation of the VTA to the ventral portion of area 6V (area 6VV) enhanced high risk-high return (HH) preference, while stimulation of the VTA to the dorsal aspect of area 6V (area 6VD) reduced the HH preference. Moreover, repeated stimulation of the VTA-6VV and VTA-area 6VD chronically enhanced and reduced the HH preference, respectively (Sasaki et al. Science, 2024). These results may reveal the neuronal mechanisms underlying addiction such as gambling disorders.