FY2019 Annual Report

Neurobiology Research Unit
Professor Jeff Wickens


The goal of the Neurobiology Research Unit is to understand the cellular mechanisms and neural circuitry underlying learning and adaptive behavior in the mammalian brain. This collaborative, interdisciplinary program of research is focused on the striatum of the basal ganglia and the neuromodulators, dopamine and acetylcholine, which play a central role in the mechanisms of reinforcement learning. Our main achievements have been: to characterize synaptic plasticity in the striatum and its modulation by dopamine; to measure dopamine signaling during learning and its role in the therapeutic mechanisms of methylphenidate; and, to show a role for cholinergic interneurons of the striatum in flexible behavior. These findings are of broad, general significance for the neuroscience of learning and motivation, and of fundamental importance for clinical understanding of major neuropsychiatric disorders. Our research has the forward goal of developing better treatments for attention-deficit hyperactivity disorder and Parkinson’s disease, which are debilitating neurological disorders of great importance to children and adults.

1. Staff

  • Dr Andres Carrasco, Staff Scientist
  • Dr. Atsushi Tamura, Postdoctoral Scholar
  • Dr Julie Chouinard, Postdoctoral Scholar
  • Dr. Nobuyoshi Kitamura, Engineer
  • Dr. Kiyoto Kurima, Specialist (Technical Staff)​
  • Ms. Yumiko Akamine, Technical Staff
  • Mr. Kavinda Liyanagama, Computer Programmer (Technical Staff)
  • Dr. Mayank Aggarwal, Junior Research Fellow
  • Ms. Sakurako Watanabe, PhD Student (JSPS scholarship recipient)
  • Dr. Stefan Pommer, Junior Research Fellow
  • Ms. Yoriko Yamamura, PhD Student (JSPS scholarship recipient)
  • Ms. Lorena Andreoli, PhD Student
  • Ms. Bozena Silic, PhD Student
  • Mr. Mao-Ting Hsu, PhD Student
  • Mr. Dvyne Nosaka, PhD Student
  • Ms. Yukako Suzuki, Research Unit Administrator

2. Collaborations

2.1 Focused ultrasound non-invasive stimulation

  • Description: Effects on deep brain structures
  • Type of collaboration: Joint research
  • Researchers:
    • Dr Jorge Moll, D'or Institute for Research and Education, Brazil
    • Professor Jeff Wickens, OIST

2.2 Human Frontier Science Program

  • Description: Spatiotemporal neurochemical dynamics of behavioral flexibility in the striatum
  • Type of collaboration: Joint research [2019-2022]
  • Researchers:
    • Dr Joshua A. Goldberg, Dept. of Medical Neurobiology-IMRIC- The Faculty of Medicine, Jerusalem, Israel
    • Dr Lin Tian, Dept. of Biochemistry and Molecular Medicine. Tian Lab, University of California. Davis/School of Medicine, Davis, USA
    • Professor Jeff Wickens, OIST

2.3 Dopamine signaling and mechanism of pyschostimulant action

  • Type of collaboration: Joint research
  • Researchers:
    • Professor Brian Hyland, University of Otago, New Zealand
    • Professor Jeff Wickens, OIST

3. Activities and Findings

Research activity has focused on: synaptic plasticity in the corticostriatal pathway; the nature of dopamine signaling during learning; and, the dynamics of neural assemblies in the striatum and their significance for behavior. We have also initiated collaborative studies with other researchers at OIST. These include work on a nanoparticle based drug delivery system for translating our basic science insights into new treatment approaches; and human imaging studies to test theories of altered reward processing in attention-deficit hyperactivity disorder. We use a powerful and unique combination of approaches extending from cellular to behavioral levels of biological organization, including 2-photon microscopy, electrophysiology, fast-scan cyclic voltammetry, behavior, optogenetics and computational modeling, taking advantage of the opportunities for cross-disciplinary research at OIST.

4. Publications

4.1 Journals

  1. Aggarwal, M., Akamine, Y., Liu, A.W., Wickens, J.R. The nucleus accumbens and inhibition in the ventral tegmental area are crucial for the Kamin blocking effect. European Journal of Neuroscience, Accepted for publication. DOI: 10.1111/ejn.14732 (2020).
  2. Perk, C.G., Wickens, J.R., Hyland, B.  Responses of putative medium spiny neurons and fast spiking interneurons to reward-related sensory signals in Wistar and genetically hyperactive rats. European Journal of Neuroscience, Accepted for publication. DOI: 10.1111/ejn.14710 (2020).  https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.14710?af=R
  3. Furukawa, E., da Costa, R.Q.M., Bado, P., Hoefle, S., Vigne, P., Monteiro, M., Wickens, J.R., Moll, J., Tripp, G., Mattos, P.  Methylphenidate modifies reward cue responses in adults with ADHD: An fMRI study. Neuropharmacology 162, 107833 (2020).  https://www.sciencedirect.com/science/article/pii/S0028390819303995
  4. Carrasco, A., Tamura, A., Pommer, S., Chouinard, J.A., Kurima, K., Barzaghi, P., Wickens, J.R. Multiparametric assessment of the impact of opsin expression and anesthesia on striatal cholinergic neurons and auditory brainstem activity. Journal of Comparative Neurology 528, 787-804 (2019).
  5. Shindou, T., Shindou, M., Watanabe, S., Wickens, J. A silent eligibility trace enables dopamine-dependent synaptic plasticity for reinforcement learning in the mouse striatum. European Journal of Neuroscience 49, 726-736 (2019).
  6. Shindou, T., Ochi-Shindou, M., Murayama, T., Saita, E.I., Momohara, Y., Wickens, J.R., Maruyama, I.N. Active propagation of dendritic electrical signals in C. elegans. Scientific Reports 9, 3430 (2019).
  7. Mackay, S.M., Myint, D.M.A., Easingwood, R.A., Hegh, D.Y., Wickens, J.R., Hyland, B.I., Jameson, G.N.L., Reynolds, J.N.J., Tan, E.W. Dynamic control of neurochemical release with ultrasonically-sensitive nanoshell-tethered liposomes. Communications Chemistry 2. (2019)  https://www.nature.com/articles/s42004-019-0226-0
  8. Igarashi, M., Wickens, J.R. Kinematic analysis of bimanual movements during food handling by head-fixed rats. Journal of Neurophysiology 121, 490-499 (2019).
  9. Fuller, J.A., Burrell, M.H., Yee, A.G., Liyanagama, K., Lipski, J., Wickens, J.R., Hyland, B.I. Role of homeostatic feedback mechanisms in modulating methylphenidate actions on phasic dopamine signaling in the striatum of awake behaving rats. Progress in Neurobiology 182, 101681. (2019) https://doi.org/10.1016/j.pneurobio.2019.101681
  10. Aoki, S., Smith, J.B., Li, H., Yan, X., Igarashi, M., Coulon, P., Wickens, J.R., Ruigrok, T.J., Jin, X. An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway. eLife 2019;8:e49995 doi: 10.7554/eLife.49995 (2019).  https://doi.org/10.7554/eLife.49995.001

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. Wickens, J.R., Chouinard, J., Kitamura, N., Liyanagama, K., Tian, L. Striatal dopamine in time and space: effects of methylphenidate. Neuroscience 2019, Chicago, USA.  October 19-23, 2019 (2019).
  2. Chouinard, J.A., Marvin, J.S., Borden, P.M., Looger, L.L., Wickens, J.R.  Real-time visualization of acetylcholine in acute striatal slices using iAChSnFR: a new robust genetically-encoded fluorescent sensor.  Neuroscience 2019, Chicago, USA. October 19-23, 2019 (2019). 
  3. Carrasco, A., Wickens, J.R. Cholinergic neurons in the dorsal subiculum of transgenic ChAT-cre mice. IBRO 2019 World Congress of Neuroscience, Daegu, South Korea, September 21-25, 2019 (2019).
  4. Wickens, J.R., Shindou, T., Ochi-Shindou, M., Watanabe, S.  Timing of dopamine directs synaptic plasticity.  CNS Computational Neuroscience Meeting, Barcelona, Spain, July 13-17, 2019 (2019).
  5. Tamura, A., Kurima, K., Akamine, Y., Wickens, J.R.  Pause in cholinergic firings modulate the direction of corticostriatal synaptic plasticity in dorsomedical striatum. [背内側コリン作動性ニューロンは発火の停止により皮質線条体シナプス可塑性の方向性を調節する」NEURO2019, Niigata-City, Japan, July 25-28, 2019 (2019).
  6. Carrasco, A., Wickens, J.R. Cholinergic neurons in the dorsal subiculum of transgenic ChAT-cre mice. IBNS Annual Meeting, Cairns, Australia, June 23-27, 2019 (2019).
  7. Watanabe, S., Wickens, J.R. Interaction of multiple cortical and dopaminergic inputs in striatal spike timing-dependent plasticity. 2019 Nordic Neuroscience Meeting, Helsinki, Finland, June 12-14, 2019 (2019).
  8. Tamura, A., Kurima, K., Akamine, Y., Wickens, J.R.  Pause in cholinergic firings modulate the direction of corticostriatal synaptic plasticity in dorsomedical striatum. XIIIth IBAGS Meeting, Biarritz, France, April 28-May 2, 2019 (2019).

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

6.1 Seminar by Prof. James Tepper

  • Title of Talk: "Neurophysiology and Synaptic Connections of Striatal Interneurons"
  • Date: January 16, 2020. 11:00-12:00.
  • Venue: OIST Campus Lab1 (D015)
  • Speaker: Professor James Tepper. Rutgers, The State University of Newark

6.2 PhD Thesis Presentation by Mr. Stefan Pommer

  • Title of Talk: "The effect of serotonin receptor 5-HT1b on lateral inhibition between spiny projection neurons in the mouse striatum"
  • Date: January 15, 2020. 14:00-15:00.
  • Venue: OIST Campus Lab1 (B503)
  • Speaker: Mr Stefan Pommer. Neurobiology Research Unit, OIST

6.3 Seminar by Prof. Tom Beckers

  • Title of Talk: ”Replication, verification, and tribulation: A case study of the reactivation-extinction effect (aka, the story behind a strange Nature addendum)”
  • Date: October 9, 2019. 11:00-12:00.
  • Venue: OIST Campus Lab3 (C700)
  • Speaker: Professor Tom Beckers. KU Leuven

6.4 PhD Thesis Presentation by Mr. Mayank Aggarwal

  • Title of Talk: "The Role of Ventral Tegmental Area and Nucleus Accumbens in the Kamin Blocking Effect"
  • Date: October 8, 2019. 09:00-10:00.
  • Venue: OIST Campus Lab3 (C700)
  • Speaker: Mr Mayank Aggarwal. Neurobiology Research Unit, OIST

6.5 Seminar by Prof. Bernard Balleine

  • Title of Talk: "A novel form of cellular memory necessary for the influence of reward learning on decision-making"
  • Date: October 7, 2019. 15:00-16:00.
  • Venue: OIST Campus Lab1 (C015)
  • Speaker: Professor Bernard Balleine. University of New South Wales, Department of Psychology

7. Other

Thank you for supporting us for on-going research activities at OIST.

Lab Members contributed to teaching as part of External Professional Activities at University of Ryukyu's in fiscal year 2019.

  • University of Ryukyu's delegated Dr Andres Carraso the teaching in academic program of Medical English(15 session) as a part-time lecturer.
  • University of Ryukyu's delegated Dr Kiyoto Kurima the teaching in academic program of Pathology as a part-time lecturer.

In November 16, 2019, OIST Event of Science Festa was well-received by children and visitors.  Our lab members spent precious time with local people and children. Our Booth was packed with many children and it was quite popular.  Our major interest is in field of neuroscience. At event of Science Festa, we tried performance of mysterious Chemistry Magic using chemical to make toothpaste for elephants, and this year we added photo booth.   Children enjoyed taking photographs, dressing-up in lab coat, safety glasses, surgical gloves, and wore a little big size surgical mask.  Children tried some pipetting using real gear, GI●SON Pipette!  Children were just like real scientist/technician!   Thank you to all children and parents. 

OIST Ocean Outreach (OIST Communication and Public Relations)
At end of January, 2020, our colleague of Dr Julie Chouinard accompanied our Community Relations staff in Miyako Island, Okinawa.  We received opportunity to share time with islands's locals, our member Julie Chouinard introduced "Mysterious Chemistry Magic!"
elephant toothpast :)

Photo: Miyako Island, OIST Ocean Outreach.