FY2022 Annual Report

Neurobiology Research Unit
Professor Jeff Wickens

A view from OIST campus



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 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
  • Tanomi Yamamura, 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 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.

2.2 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.

Highlights of the current year include a three-dimensional spatial analyses of cholinergic neuronal distributions in the brain, particularly focussing on the CINs in the striatum, and a behavioral study of conditioned approach behavior of the spontaneously hypertensive rat (SHR) model for ADHD, compared to Sprague-Dawley (SD) rats. Ongoing work includes measurement of acetylcholine release in the striatum in response to electrical stimulation in brain slices, and in vivo during awake behavior, a study of the effects of CINs on dopamine dependent synaptic plasticity in the striatum, and further investigation of the role of CINs in flexible behavior and contextual learning. We are also continuing to work on a comparison of dopamine release in the SHR and SD rat in response to primary rewards and reward-predicting cues.


4. Publications

4.1 Journals


Ponzi, A., Wickens J.R. (2022)  Ramping activity in the Striatum. Front. Comput. Neurosci., https://doi.org/10.3389/fncom.2022.902741.

Carrasco, A., Oorschot, D.E., Barzaghi, P., Wickens, J.R. (2022) Three-Dimensional Spatial Analyses of Cholinergic Neuronal Distributions Across The Mouse Septum, Nucleus Basalis, Globus Pallidus, Nucleus Accumbens, and Caudate-Putamen.  Neuroinformatics(2022)

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

Furukawa, E., Bado, P., da Costa, R.Q.M., Melo, B., Erthal, P., de Oliveira, I.P., Wickens, J.R., Moll, J., Tripp, G., Mattos, P. (2022) Reward modality modulates striatal responses to reward anticipation in adhd: Effects of affiliative and food stimuli. Psychiatry Research: Neuroimaging 327, 111561.

Silic, B., Aggarwal, M., Liyanagama, K., Tripp, G., Wickens, J.R. (2023) Conditioned approach behavior of SHR and SD rats during Pavlovian conditioning. Behavioural Brain Research 443, 114348.

Matityahu, L., Gilin, N., Atamna, Y., Tiroshi, L., Wickens, J.R., Goldberg, J.A. (2022) Mechanism of dopamine traveling waves in the striatum: Theory and experiment. bioRxiv, 2022.2004. 2019.488647.

Sieveritz,B,  Duke, SH, Wickens, JR, Arbuthnott GW (2022) Ventral motor thalamic input to prelimbic cortex mediates cost-benefit decision-making in rats.  bioRxiv 2022.02.11.480170; doi: https://doi.org/10.1101/2022.02.11.480170 


4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. Wickens, J. (2022) Dopamine and acetylcholine: enigmantic modulators of the striatum. Invited Lecture. Swedish Basal Ganglia Society Online Webinar 25th February 2022
  2. Tsu, M-T, Tanaka, K.Z., Wickens, J.R. (2022)  The role of striatum in social hierarchy formation in mice. SfN2022 San Diego

5. Intellectual Property Rights and Other Specific Achievements


Reynolds, J.N.J., Tan, E.W., Hyland, B.I., Jameson, G.N.L., Myint, M.M.A., Mackay, S.M., Wickens, J.R. (2022) Acoustic driven drug delivery systems. US Patent App. 17/579,832.

6. Meetings and Events

Nothing to report

7. Other

Nothing to report