FY2018 Annual Report

Neurobiology Research Unit
Professor Jeff Wickens

Abstract

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, Technical Staff​
  • Yumiko Akamine, Technical Staff
  • Kavinda Liyanagama, Technical Staff
  • Mayank Aggarwal, PhD Student(JSPS scholarship recipient)
  • Sakurako Watanabe, PhD Student (JSPS scholarship recipient)
  • Stefan Pommer, PhD Student
  • Masakazu Igarashi, PhD Student (JSPS scholarship recipient)
  • Yoriko Yamamura, PhD Student (JSPS scholarship recipient)
  • 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 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. Shindou, Tomomi., Ochi-Shindou, Mayumi., Watanabe, Sakurako., Wickens, Jeffery R.  A silent eligibility trace enables dopamine-dependent synaptic plasticity for reinforcement learning in the mouse striatum. Eur J Neurosci.  doi: 10.1111/ejn.13921 (2018).
  2. Aoki, Sho., Liu, Andrew W., Akamine, Yumiko., Zucca, Aya., Zucca, Stefano., Wickens, Jeffery R.  Cholinergic interneurons in the rat striatum modulate substitution of habits. Eur J Neurosci.  doi: 10.1111/ejn.13820  (2018).
  3. Zucca, Aya., Zucca, Stefano., Wickens, Jeffery R.  Cholinergic mechanisms in adaptive behaviour.  Eur J Neurosci.  doi: 10.1111/ejn.13926 (2018).
  4. Zucca, Stefano., Zucca, Aya., Nakano, Takashi., Aoki, Sho., Wickens, Jeffery R.  Pauses in cholinergic interneuron firing exert an inhibitory control on striatal output in vivo.  Elife.  doi: 10.7554/eLife.32510 (2018).
  5. Igarashi, Masakazu., Wickens, Jeffery R.  Kinematic analysis of bimanual movements during food handling by headfixed rats.  Journal of Neurophysiology.  doi:10.1152/jn.00295 (2018).
  6. Shindou, Tomomi., Ochi-Shindou, Mayumi., Murayama, Takashi., Saita, Ei-ichiro., Momohara, Yuto., Wickens, Jeffery R., Maruyama, Ichiro N.   Active propagation of dendritic electrical signals in C. elegans.  SCIENTIFIC REPORTS.  DOI: 10.1038/s41598-019-40158-9 (2019).

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. Carrasco, Andres., Chouinard, Julie A., Tamura, Atsushi., Pommer, Stefan., Kurima, Kiyoto., Wickens, Jeffery R.  Optogenetic mouse model for the study of cholinergic modulation in auditory processing.  11th FENS Forum of Neuroscience.  Berlin, Germany, July 7-11 2018. (Poster Presentation 2018.07.09)
  2. Carrasco, Andres., Chouinard, Julie A., Tamura, Atsushi., Pommer, Stefan., Kurima, Kiyoto., Wickens, Jeffery R.  Auditory brain stem responses in ChAT-Cre and ChAT-ChR2(Ai32) mice.  41th Annual Meeting of the Japan Neuroscience Society.   Kobe, Japan. July 26-29 2018. (Poster Presentation 2018.07.28)
  3. Igarashi, Masakazu., Wickens, Jeffery R.  The role of anterior corpus callosum in bimanual coordination in head-fixed rats.  Salk Institute for Biological Studies, Molecular Neurobiology Lab.  San Diego, USA.  July 20 2018.
  4. Wickens, Jeffery R., Fuller, Justine A., Burrell, M H., Yee, A., Lipski, J., Hyland, Brian I.  Negative feedback shapes methylphenidate effects on phasic dopamine signalling in the striatum.  Konkuk University, School of Medicine, Department of Pharmacology. Seoul, South Korea.  October 2 2018.
  5. Igarashi, Masakazu., Akamine, Yumiko., Wickens, Jeffery R.  The role of anterior corpus callosum in bimanual coordination in head-fixed rats.  Society for Neuroscience SfN NEUROSCIENCE 2018.  November 3-7 2018. (Unable to Attend 2018.11.06)
  6. Pommer, Stefan., Wickens, Jeffery R.  Serotonin 5-HT1B receptors decrease lateral inhibition in the mouse striatum by reducing the probability of GABA release from spiny projection neurons.  Society for Neuroscience SfN NEUROSCIENCE 2018.  November 3-7 2018.  (Poster Presentation 2018.11.04)
  7. Tamura, Atsushi., Kurima, Kiyoto., Akamine, Yumiko., Wickens, Jeffery R.  Two groups of SPNs in cholinergic modulation of corticostriatal plasticity in dorsomedial striatum.   9th FAOPS Congress Federation of the Asian and Oceanian Physiological Societies  Kobe, Japan.  March 28-31 2019. (Poster Presentation 2019.03.30)
     

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report
 

6. Meetings and Events

6.1 SEMINAR  ”THE FUNCTIONAL ORGANIZATION AND PLASTICITY OF RODENT MOTOR CORTEX”

  • Date: January 15, 2019
  • Venue: OIST Campus Lab3, Seminar Room B700
  • Speaker: Dr. Gordon Teskey (University of Calgary. Canada)

6.2 SEMINAR ”Age-related changes in brain function and connectivity in relation to motor behavior”

  • Date:  January 17, 2019
  • Venue: OIST Campus Center Bldg, Seminar Room C210
  • Speaker: Dr. Stephan Swinnen (Movement Control & Neuroplasticity Research Center at Group Biomedical Sciences KU Leuven. Belgium)

6.3 SEMINAR ”Population dynamics and entrainment of basal ganglia pacemakers are shaped by their dendritic arbors”

  • Date:  February 27, 2019
  • Venue: OIST Campus Lab1, Seminar Room D014
  • Speaker: Dr. Joshua Goldberg (Department of medical Neurobiology, The Hebrew University of Jerusalem. Israel)
     

7. Other

Nothing to report.