FY2021 Annual Report

Neurobiology Research Unit
Professor Jeff Wickens

Ocean view from OIST campus, 2022, June
After rainfaill season

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. Nobuyoshi Kitamura, Staff Scientist
  • Dr Julie Chouinard, Postdoctoral Scholar
  • Dr Gideon Sarpong, Postdoctoral Scholar
  • Dr Rachel Pass, Postdoctoral Scholar
  • Kiyoto Kurima, Technical Staff​
  • Yumiko Akamine, Technical Staff
  • Kavinda Liyanagama, Technical Staff
  • Yori Yamamura, PhD Student
  • Lorena Andreoli, PhD Student
  • Bozena Silic, PhD Student
  • Dvyne Nosaka, PhD Student
  • Mao-Ting Hsu, PhD Student
  • Kang-Yu Chu, PhD Student
  • Arjun Manish, Joshi, PhD Student
  • Yukako Suzuki, Research Unit Administrator
     

2. Collaborations

2.1 Focused ultrasound non-invasive stimulation

  • Description: Effects of ultrasound on deep brain structures
  • Type of collaboration: Joint research
  • Researchers:
  1. Dr Jorge Moll, Mr Clayton Teixeira, D'or Institute for Research and Education, Brazil.
  2. Professor Jeff Wickens, Gail Tripp, Emi Furukawa, 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:
  1. Dr Joshua A. Goldberg, Dept. of Medical Neurobiology-IMRIC- The Faculty of Medicine, Jerusalem, Israel.
  2. Dr Lin Tian, Dept. of Biochemistry and Molecular Medicine. Tian Lab, University of California. Davis/School of Medicine, Davis, USA.
  3. Professor Jeff Wickens, OIST.

2.3 Dopamine signaling and mechanism of pyschostimulant action

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

3. Activities and Findings

 

Our overarching aim is to investigate the neural mechanisms of the striatum of the basal ganglia, and to understand the contribution of these mechanisms to reinforcement learning and behavioral flexibility. As the main input nucleus of the basal ganglia, the striatum receives sensory, cognitive, and motor information from cortical and thalamic afferents, which synapse directly on the output neurons of the striatum, the spiny projection neurons (SPNs). The GABAergic SPNs receive reward signals from midbrain dopaminergic neurons and contextual information from intrinsic cholinergic interneurons (CINs). The SPNs are the principal output neurons of the striatum, and additionally form a lateral inhibitory network with other SPNs via their local axon collaterals. Multiple subtypes of GABA interneurons complete this circuitry. The input-output information processing operation performed by the striatum is not fully understood, but we speculate that this anatomy provides a matrix of modifiable input-output connections which compete for control of output, forming a substrate for stimulus-response learning in the dorsolateral striatum, goal-directed learning in the dorsomedial striatum, and reward-related learning in the ventral striatum.

 

4. Publications

4.1 Journals

  1. Reynolds, J.N.J., Avvisati, R., Dodson, P., Fisher, S., Oswald, M. Wickens, J.R., Zhang, Y. (2022) Coincidence of cholinergic pauses, dopaminergic activation and depolarisation of spiny projection neurons drives synaptic plasticity in the striatum. Nature Communcations, Nature Communications 13 (1), 1-9

  2. Nakano, T., Rizwan, S. B., Myint, D., Gray, J., Mackay, S., Harris, P., Perk, C., Hyland, B.I., Empson, R., Tan, E.W., Dani, K., Reynolds, J.N.J., Wickens J.R. (2022) An on-demand drug delivery system for control of epileptiform seizures, Pharmaceutics, 14 (2), 468

  3. Nosaka, D., Wickens, J.R. (2022) Striatal Cholinergic Signaling in Time and Space. Molecules 27 (4), 1202

  4. Pommer, S., Akamine, Y., Schiffmann, S.N., de Kerchove d’Exaerde, A., Wickens, J.R. (2021) The Effect of Serotonin Receptor 5-HT1B on Lateral Inhibition between Spiny Projection Neurons in the Mouse Striatum. Journal of Neuroscience, 41, 7831–7847

  5. Aggarwal, M., Wickens, J.R. (2021) Behavioral determinants in the expression of the Kamin blocking effect: Implications for associative learning theory. Neuroscience & Biobehavioral Reviews 124, 16-34

  6. Perk, C.G., Wickens, J.R., Hyland, B. (2021) Responses of putative medium spiny neurons and fast spiking interneurons to reward-related sensory signals in Wistar and genetically hypertensive rats. European Journal of Neuroscience,  53 (7), 2165-2177

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. Chouinard, J.A., Takahashi, S., Kurima, K., Liyanagama, K., Kitamura, N., Tian, L., Wickens, J.R., "Dopamine distribution in time and space: effects of methylphenidate", Virtual sfn conference, October 8-16, 2021 (2021).
  2. Chouinard, J.A., Takahashi, S., Kurima, K., Liyanagama, K., Kitamura, N., Tian, L., Wickens, J.R., "Striatal dopamine in time and space: effects of methylphenidate", Virtual Dopamine Conference (ViDA),  (2021).
     

5. Intellectual Property Rights and Other Specific Achievements

PATENT
Acoustic driven drug delivery systems

JNJ Reynolds, EW Tan, BI Hyland, GNL Jameson, MMA Myint, ...
US Patent 11,260,126
2022/3/1

6. Meetings and Events

Nothing to report

 

7. Other

Nothing to report