Tadashi Isa

Research Overview

Motor systems are developed for individual animal species to best fit their living environment. We are studying the neural circuits controlling the fine motor skills, which are especially developed in higher primates, that is, dexterous hand movements and saccadic eye movements　 using non-human primate model. We also study the cognitive functions related to the control of these movements, such as attention and motivation, and also the mechanism of functional recovery after injury of the neural systems. First, dexterous hand movements, the ability to independently control individual fingers, are specially developed in higher primates and considered to be based on the interplay between the evolutionally novel pathway, that is the direct connection from the motor cortex to spinal motor neurons, and other old descending motor pathways, originating from the brain stem and spinal cord. We are studying how these parallel systems are coordinated with each other. We are also studying how the evolutionally old systems can compensate for the impaired function of the new systems in case of brain and spinal cord injury. Second, saccadic eye movements are normally controlled by visual inputs through the visual cortex. However, it is known that after damage to the visual cortex, saccadic eye movements can recover, however, without conscious perception of the objects, the phenomenon called “blindsight”. We have clarified that blindsight is supported by phylogenetically old visual systems centered on the superior colliculus in the midbrain. We are studying the large-scaled network underlying blindsight and how kind of functions are preserved and impaired and state of consciousness in blindsight. In ASHBi, on top of these preceding studies, we will try to elucidate the genetic basis of the evolution of these motor systems using single cell RNA-seq of homologous neurons in rodents and primates, and generating and analyzing the knock-down macaque monkeys by genome editing of the key genes for the evolution.

Figure 1: Recovery of dexterous hand movements after lesion of the direct connection from the primary motor cortex (M1) to hand motoneurons (MNs)（red line）. Hand movements are once impaired, but recover in 1-3 months. Abbreviations; NAc = nucleus accumbens, PN = propriospinal neurons, PM = premotor cortex, RSN = reticulospinal neurons

Figure 2: Recovery of saccadic eye movements after unilateral lesion of the primary visual cortex (red cross), the time course of which is shown below. After V1 lesion, the lateral geniculate nucleus （＝LGN）-extrastriate cortical pathway, and superficial layer of the superior colliculus (sSC)-pulvinar (Pul)- extrastriate cortical pathway are involved in the recovery. Abbreviations; CD=caudate nucleus, dSC = deeper layer of the superior colliculus, FEF=frontal eye field, LIP=lateral intraparietal area, RF=reticular formation, SNr=substantia nigra pars reticulalta

Publications

Isa, T. (2019) Dexterous hand movements and their recovery after central nervous system injury. Annual Review of Neuroscience, in press.

Kinoshita, M., Kato, R., Isa, K., Kobayashi, K., Kobayashi, K., Onoe, H. and Isa, T. (2019) Dissecting the circuit for blindsight to reveal the critical role of pulvinar and superior colliculus. Nature Communications, 10(1):135. doi: 10.1038/s41467-018-08058-0.

Tohyama, T., Kinoshita, M., Kobayashi, K., Isa, K., Watanabe, D., Kobayashi, K., Liu, M. and Isa, T.(2017) Contribution of propriospinal neurons to recovery of hand dexterity after corticospinal tract lesions in monkeys.Proceedings of National Academy of Science USA,114:604-609.

Sawada, M., Kato, K., Kunieda, T., Mikuni, N., Miyamoto, S., Onoe, H., Isa, T. and Nishimura, Y. (2015) Function of nucleus accumbens in motor control during recovery after spinal cord injury. Science, 350: 98-101.

Kinoshita, M., Matsui, R., Kato, S., Hasegawa, T., Kasahara, H., Isa, K., Watakabe, A., Yamamori, T., Nishimura, Y., Alstermark, B., Watanabe, D., Kobayashi, K. and Isa, T. (2012) Genetic dissection of the circuit for hand dexterity in primates. Nature, 487: 235-238.