Division of Neurobiology and Physiology,
Department of Neuroscience,
Graduate School of Medicine
in Kyoto University

Projects

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Project 01

Recovery from brain & spinal cord injury

Using a macaque monkey model with lesion of the corticospinal tract is transected at the cervical cord, we are studying the neural mechanism of large-scaled neural network reorganization for recovery of dexterous hand movements which spans not only the spinal cord, but also bilateral motor cortices and even the meso-limbic structures such as the nucleus accumbens.

Recent Publications

Ueno, S., Yamaguchi, R., Isa, K., Kawasaki, T., Mitsuhashi, M., Kobayashi, K., Takahashi, J., & Isa, T. (2024). Supraspinal Plasticity of Axonal Projections From the Motor Cortex After Spinal Cord Injury in Macaques. The Journal of comparative neurology, 532(12), e70007. https://doi.org/10.1002/cne.70007

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Mitsuhashi, M., Yamaguchi, R., Kawasaki, T., Ueno, S., Sun, Y., Isa, K., Takahashi, J., Kobayashi, K., Onoe, H., Takahashi, R., & Isa, T. (2024). Stage-dependent role of interhemispheric pathway for motor recovery in primates. Nature communications, 15(1), 6762. https://doi.org/10.1038/s41467-024-51070-w

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Suzuki M, Onoe K, Sawada M, Takahashi N, Higo N, Murata Y, Tsukada YH, Isa T, Onoe H, Nishimura Y (2020) The ventral striatum is a key node of cortical reorganization required for functional recovery of finger dexterity after spinal cord injury in monkeys. Cerebral Cortex, 30:3259-3270. 

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Member

Tadashi Isa , Reona Yamaguchi , Masahiro Mitsuhashi , Satoko Ueno , Stefan Peyda , Kohei Matsuda

Project 02

Neural mechanism of blindsight

Some patients with damage to the primary visual cortex (V1) were shown the ability to perform goal directed movements such as reaching and saccadic eye movements toward the objects presented in the blind field, called “blindsight. We apply multiple techniques to the macaque monkeys with unilateral lesion of .V1 to clarify the neural circuits for the blindsight and how much of the cognitive functions such as short term memory, decision making, attention and visual awareness are retained in blindsight condition.

Recent Publications

Kato R, Zeghbib A, Redgrave P, Isa T (2021) Visual instrumental learning in blindsight monkeys. Scientific Reports 11, 14819.

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Isa T, Yoshida M (2021) Neural mechanism of blindsight in a macaque model. Neuroscience, (Forefront review), 469: 138-161.

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Kato R, Hayashi T, Onoe K, Yoshida M, Tsukada H, Onoe H, Isa T, Ikeda T (2021) The posterior parietal cortex contributes to visuomotor processing for saccades in blindsight macaques. Communications Biology, 4:278

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Member

Tadashi Isa , Xiyao Yu , Zhang Yuxin

Project 03

Neural mechanism of flexible decision making

Our life is sustained by the ability of flexible decision making depending on the environment. Using “the hidden target search task with changing goals”, we are studying the neural basis of explorative and exploitive decision making, and using the “risk choice task”, we are studying the neural basis of decision making between high risk-high return versus low risk-low return conditions.

Recent Publications

Ryo Sasaki, Yasumi Ohta, Hirotaka Onoe, Reona Yamaguchi, Takeshi Miyamoto, Takashi Tokuda, Yuki Tamaki, Kaoru Isa, Jun Takahashi, Kenta Kobayashi, Jun Ohta, Tadashi Isa. Balancing Risk-Return Decisions by Manipulating the Mesofrontal Circuits in Primates. Science383,32-33(2024).

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Takakuwa N, Redgrave P, Isa T; Cortical visual processing evokes short-latency reward-predicting cue responses in primate midbrain dopamine neurons.; Sci Rep; 2018 Oct 8

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Takakuwa N, Kato R, Redgrave P, Isa T; Emergence of visually-evoked reward expectation signals in dopamine neurons via the superior colliculus in V1 lesioned monkeys.; Elife; 2017 Jun 19

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Member

Tadashi Isa , Masanobu Ishio

Project 04

Eye movement and attention systems in common marmosets

Common marmoset are considered as a new nonhuman primate model for life science studies in which techniques to generate genetically modified animals were developed. We take advantage of marmosets having a small and liscencephalic brain (having no sulci), and are studying the neural systems controlling eye movements and visual attention. The results are expected to contribute to establishing the novel biomarkers of the neuropsychatric disorders.

Recent Publications

Amly, W., Chen, C. Y., & Isa, T. (2024). Modeling saccade reaction time in marmosets: the contribution of earlier visual response and variable inhibition. Frontiers in systems neuroscience, 18, 1478019. https://doi.org/10.3389/fnsys.2024.1478019

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Chen C-Y, Matrov D, Veale R, Onoe H, Yoshida M, Miura K, Isa T* (2021) Properties of visually-guided saccadic behavior and bottom-up attention in marmoset, macaque, and human. Journal of Neurophysiology, 125:437-457. 

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Member

Tadashi Isa , Masatoshi Kasai , Richard Veale , CHEN Chih-Yang , Wajd Amly , HO Kuan-Ting

Project 05

Structure and function of the superior colliculus

The midbrain superior colliculus is a phylogenetically ancient brain structure, which is homologous to the optic tectum in fish, amphibians, reptiles and birds, and is involved in the processing of innate sensory and motor functions in vertebrates. Its superficial layer receives primarily visual inputs and its deeper layers receive non-visual sensory inputs and projects descending motor commands to the brainstem and spinal cord. We have been studying the structure and functions of its local circuits and functions of the input and output systems by integrating the multiple methods spanning from electrophysiology in acute in vivo slice preparations, in either awake or anesthetized preparations, circuit manipulation with optogenetic and chemogenetic techniques, 2-photon laser scanning microscopes and large-scaled network simulations.

Recent Publications

Kasai M, Isa T (2021) Effects of light isoflurane anesthesia on organization of direction and orientation selectivity in the superficial layer of the mouse superior colliculus, Journal of Neuroscience, JN-RM-1196-21

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Tokuoka K, Kasai M, Kobayashi K, Isa T. Anatomical and electrophysiological analysis of cholinergic projections from the parabigeminal nucleus to the superficial superior colliculus. J Neurophysiol. 2020 Dec 1;124(6):1968-1985.

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Isa K, Sooksawate T, Kobayashi K, Kobayashi K, Redgrave P, Isa T (2020) Dissecting the tectal output channels for orienting and defense responses. eNeuro, 7(5) :ENEURO.0271-20.2020. 

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Member

Tadashi Isa , Masatoshi Kasai , Kaoru Isa

Project 06

Development of selective circuit manipulation techniques

Recent development of circuit manipulation techniques with optogenetics or chemogenetics enabled us to demonstrate the functions of particular circuits selectively and causally by using genetically modified animals and viral vectors in model animals as represented by rodents. However, these cutting-edge techniques are not still fully available in nonhuman primates. To further advance our understanding of higher cognitive functions, it is critical to make these techniques fully available in nonhuman primates. We combined viral vectors and succeeded in manipulating a particular neural pathway in the spinal cord of macaque monkeys and affected the behavior for the first time in the world (Kinoshita et al. Nature 2012). We are further developing these techniques to be useful in a variety of neural circuits of the primate brain.

Recent Publications

Koshimizu Y, Isa K, Kobayashi K, Isa T (2021) Double viral vector technology for selective manipulation of neural pathways with higher level of efficiency and safety. Gene Therapy, 28:339-350. Epub 2021 Jan 11.

DOI PUBMED

Isa K, Sooksawate T, Kobayashi K, Kobayashi K, Redgrave P, Isa T (2020) Dissecting the tectal output channels for orienting and defense responses. eNeuro, 7(5) :ENEURO.0271-20.2020. 

DOI PUBMED

Kinoshita M, Kato R, Isa K, Kobayashi K, Kobayashi K, Onoe H, Isa T; Dissecting the circuit for blindsight to reveal the critical role of pulvinar and superior colliculus.; Nat Commun; 2019 Jan 11

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Member

Tadashi Isa , Kaoru Isa

Project 07

Other projects -1-

(1) Species differences in the structure of sensori-motor systems
We have been studying the connectivity and gene expression of sensori-motor systems, especially the pyramidal systems in different animal species in health and disease.

Recent Publications

Sugiyama Y, Oishi T, Yamashita A, Murata Y, Yamamoto T, Takashima I, Isa T, Higo N; Neuronal and microglial localization of secreted phosphoprotein 1 (osteopontin) in intact and damaged motor cortex of macaques.; Brain Res; 2019 Jul 1

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Umeda T, Isa T, Nishimura Y; The somatosensory cortex receives information about motor output.; Sci Adv; 2019 Jul

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Yoshida Y, Isa T; Neural and genetic basis of dexterous hand movements.; Curr Opin Neurobiol; 2018 Oct

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Project 08

Other projects -2-

(2) Information processing in the sensorimotor systems revealed by decoding methods
We have been studying how the information is processed among the sensory and motor systems in macaque monkeys using multi-channel recording and decoding techniques.

Recent Publications

Sugiyama Y, Oishi T, Yamashita A, Murata Y, Yamamoto T, Takashima I, Isa T, Higo N; Neuronal and microglial localization of secreted phosphoprotein 1 (osteopontin) in intact and damaged motor cortex of macaques.; Brain Res; 2019 Jul 1

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Umeda T, Isa T, Nishimura Y; The somatosensory cortex receives information about motor output.; Sci Adv; 2019 Jul

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Yoshida Y, Isa T; Neural and genetic basis of dexterous hand movements.; Curr Opin Neurobiol; 2018 Oct

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